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Objectives Methods Results Conclusion To characterize the impact of prior exposure and refractoriness to lenalidomide or proteasome inhibitors (PIs) on the effectiveness and safety of ixazomib–lenalidomide–dexamethasone (IRd) in relapsed/refractory multiple myeloma (RRMM).INSURE is a pooled analysis of adult RRMM patients who had received IRd in ≥2 line of therapy from three studies: INSIGHT MM, UVEA‐IXA, and REMIX.Overall, 391/100/68 were lenalidomide‐naïve/−exposed/−refractory and 37/411/110 were PI‐naïve/−exposed/−refractory. Median duration of therapy (DOT) was 15.3/15.6/4.7 months and median progression‐free survival (PFS) was 21.6/25.8/5.6 months in lenalidomide‐naïve/exposed/refractory patients. Median DOT and PFS in PI‐naïve/exposed/refractory patients were 20.4/15.2/6.9 months and not reached/19.8/11.4 months, respectively. The proportion of lenalidomide‐naïve/exposed/refractory patients in INSIGHT and UVEA‐IXA who discontinued a study drug due to adverse events (AEs) was ixazomib, 31.6/28.2/28.0% and 18.6/6.7/10.5%; lenalidomide, 21.9/28.2/16.0% and 16.1/6.7/10.5%; dexamethasone, 18.4/20.5/16.0% and 10.6/0/10.5%, respectively. The proportion of PI‐naïve/exposed/refractory patients in INSIGHT and UVEA‐IXA who discontinued a study drug due to AEs was: ixazomib, 44.4/28.8/27.8% and 22.2/16.7/15.7%; lenalidomide, 33.3/22.0/19.4% and 16.7/15.9/11.8%; dexamethasone, 33.3/17.4/16.7% and 16.7/9.5/7.8%, respectively. REMIX AE discontinuation rates were unavailable.IRd appeared to be effective in RRMM patients in routine clinical practice regardless of prior lenalidomide or PI exposure, with better outcomes seen in lenalidomide‐ and/or PI‐nonrefractory versus refractory patients. [ABSTRACT FROM AUTHOR]

Summary: Myeloma patients frequently respond poorly to bacterial and viral vaccination. A few studies have reported poor humoral immune responses in myeloma patients to COVID‐19 vaccination. Using a prospective study of myeloma patients in the UK Rudy study cohort, we assessed humoral and interferon gamma release assay (IGRA) cellular immune responses to COVID‐19 vaccination post second COVID‐19 vaccine administration. We report data from 214 adults with myeloma (n = 204) or smouldering myeloma (n = 10) who provided blood samples at least three weeks after second vaccine dose. Positive Anti‐spike antibody levels (> 50 iu/ml) were detected in 189/203 (92.7%), positive IGRA responses were seen in 97/158 (61.4%) myeloma patients. Only 10/158 (6.3%) patients were identified to have both a negative IGRA and negative anti‐spike protein antibody response. In all, 95/158 (60.1%) patients produced positive results for both anti‐spike protein serology and IGRA. After adjusting for disease severity and myeloma therapy, poor humoral immune response was predicted by male gender. Predictors of poor IGRA included anti‐CD38/anti‐BCMA (B‐cell maturation antigen) therapy and Pfizer‐BioNTech vaccination. Further work is required to understand the clinical significance of divergent cellular response to vaccination. [ABSTRACT FROM AUTHOR]

All patients who had had a previous infection had a robust antibody response to the first dose of COVID-19 vaccine and 60% of patients had an optimal immune response to the first dose of COVID-19 vaccination. COVID symptoms, testing, shielding impact on patient-reported outcomes and early vaccine responses in individuals with multiple myeloma Keywords: myeloma; COVID-19; vaccination; wellbeing; shielding EN myeloma COVID-19 vaccination wellbeing shielding 95 98 4 12/27/21 20220101 NES 220101 Patients with myeloma have been shielded and self-isolated since the start of the COVID-19 pandemic, due to the concern for and subsequent reports of higher risk of severe COVID-19 disease and mortality.1 In addition, guidelines have encouraged attenuation of myeloma therapeutics or a switch to oral therapies, ostensibly to reduce hospital foot-fall, facilitate shielding and potentially to limit further treatment-related immune suppression.2 Myeloma requires ongoing immune-suppressive chemotherapy, frequent medical visits and has previously demonstrated universally poor response to vaccinations.3 The protective titre of antibodies required to prevent re-infection is unclear, as is the ability to protect patients from SARS-CoV-2 virus variants of concern (VoC). [Extracted from the article]

Objectives: To retrospectively analyze real‐world treatment patterns in patients with relapsed/refractory multiple myeloma (RRMM) who initiated third‐line treatment in Europe. Methods: German and Italian administrative claims data were sourced from the German AOK PLUS health insurance fund and Italian local health units (2016–2020). Data for the United Kingdom (UK), France, and Spain were sourced from medical chart reviews (MCRs) from 2016 to 2018 (historical) and 2019 to 2021 (new) using electronic case report forms. Results: Across all countries, immunomodulatory imide drug (IMiD)‐based regimens were prominent in the third‐line setting. From 2016 to 2020, lenalidomide‐dexamethasone was most common in Italy (18.0%) and Germany (12.7%). From 2019 to 2021, the most common regimen was ixazomib‐lenalidomide‐dexamethasone (67.5%) in the UK, pomalidomide‐dexamethasone (17.1%) in France, and daratumumab‐bortezomib‐dexamethasone (15.0%) in Spain. In the historical data (2016–2018), third‐line lenalidomide‐ and pomalidomide‐dexamethasone doublet use across the UK (>47%), France (>46%), and Spain (>33%) was high. From historical to new, triplet use increased in Spain (>19% to >60%) as did anti‐CD38 agent use in France (15.1% to 51.9%) and Spain (19.7% to 42.1%). Conclusions: From 2016 to 2021, third‐line regimens were mostly IMiD based. The MCR data demonstrated evolving treatment choices from 2016 to 2018 and 2019 to 2021, providing insights into uptake of novel agents and current RRMM European clinical practice. [ABSTRACT FROM AUTHOR]

Real-world data on regimens for relapsed/refractory multiple myeloma (RRMM) represent an important component of therapeutic decision-making. This multi-centric, retrospective, observational study conducted by the treating physicians evaluated the effectiveness and safety of ixazomib-lenalidomide-dexamethasone (IRd) in 155 patients who received ixazomib via early access programs in Greece, the UK, and the Czech Republic. Median age was 68 years; 17% had an Eastern Cooperative Oncology Group performance status ≥ 2; median number of prior therapies was 1 (range 1–7); 91%, 47%, and 17% had received prior bortezomib, thalidomide, and lenalidomide, respectively. Median duration of exposure to ixazomib was 9.6 months. Overall response rate was 74%, including 35% very good partial response or better (16% complete response). Median progression-free survival (PFS) was 27.6 months (27.6 and 19.9 months in patients with 1 or > 1 prior lines, respectively). IRd treatment for ≥ 6 months was associated with longer PFS (hazard ratio 0.06). Fourteen patients (9%) discontinued IRd due to adverse events/toxicity in the absence of disease progression. Peripheral neuropathy was reported in 35% of patients (3% grades 3–4). These findings support the results of the phase III TOURMALINE-MM1 trial in a broader real-world RRMM population. [ABSTRACT FROM AUTHOR]

Established treatments for transplant-ineligible (TNE) patients with newly diagnosed multiple myeloma (NDMM) include melphalan and prednisone (MP) combined with either bortezomib (VMP) or thalidomide (MPT), or lenalidomide plus low-dose dexamethasone (Rd). New treatments for TNE NDMM include Rd plus bortezomib (RVd) and daratumumab plus VMP (VMP + D), daratumumab plus lenalidomide and dexamethasone (D + Rd). Relative efficacy of these treatments was compared using a network meta-analysis. Eight trials identified by a systematic literature review were included in the primary analysis; hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were used. Rd was superior to other MP-based regimens for OS and PFS. There was strong evidence that, compared with Rd, both D + Rd and RVd improved PFS (HR 0.57; 95% credible interval (CrI) 0.43, 0.73 and HR 0.72; 95% CrI 0.56, 0.91, respectively). However, there was strong evidence only for RVd in respect to OS (HR 0.72; 95% CrI 0.52, 0.96). [ABSTRACT FROM AUTHOR]

This article provides information on the diagnosis and management of smouldering myeloma, a precursor condition to multiple myeloma. It discusses various diagnostic tests and imaging techniques used to identify smouldering myeloma and emphasizes the importance of restaging if there is evidence of progression. The article also provides recommendations for screening and initial investigations for suspected myeloma. Additionally, it discusses risk stratification models and treatment options for smouldering myeloma, including the use of lenalidomide. The article concludes by highlighting ongoing clinical trials and the need for further research in the treatment of smouldering myeloma. [Extracted from the article]

The article discusses clinical management and diagnosis of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) that manifest with osteoporosis and fragility fractures. Topics explored include the increasing prevalence of osteoporosis and fractures in the elderly, the standardized incidence ratio of osteoporotic fracture in patients with MGUS, and the screening guidelines for myeloma bone disease and MGUS.

Tin–germanium alloys are increasingly of interest as optoelectronic and thermoelectric materials as well as materials for Li/Na ion battery electrodes. However, the lattice incompatibility of bulk Sn and Ge makes creating such alloys challenging. By exploiting the unique strain tolerance of nanosized crystals, we have developed a facile synthetic method for homogeneous SnxGe1−x alloy nanocrystals with composition varying from essentially pure Ge to 95% Sn while still maintaining the cubic structure. [ABSTRACT FROM AUTHOR]

Quaternary MIMIIIMIVXVI4 (I–III–IV–VI4) chalcogenides obtained by cross-substitution of binary and ternary compounds remain relatively unexplored. We have for the first-time synthesized wurtzite and defect chalcopyrite phases of CuMSnS4 (M = In or Ga) in the form of nanocrystals. Optical measurements show that the CuMSnS4 (M = In or Ga) nanocrystals exhibit strong visible light absorption with band gap values between 1.15 and 1.4 eV, suitable for solar energy conversion applications. [ABSTRACT FROM AUTHOR]

Women have lower incidence of myeloma than men and the gap increases with age to >90 years in whom the M:F ratio is 2:1 (59.8:28.1/100 000 annually).8 We understand that drug risk minimisation is a global concern and changes cannot be applied unilaterally in the United Kingdom. The Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom has approved about 20 generic lenalidomide products. Current safety measures for IMiD drug prescription are resource intensive and liable to become more so with the availability of multiple new generic versions of Lenalidomide. [Extracted from the article]

Nontoxic,sustainable, and cost-effective, Group IV materials areattractive for a broad range of electronic and optoelectronic applications,although the indirect principal band gaps of silicon and germanium(Ge) present complications that impact device design and cost. Previousstudies have shown that the band structures of these materials canbe modified by the influence of quantum confinement in nanostructuresor by alloying with tin (Sn) in metastable thin films; to date, neithermethod has produced a material with a direct band gap of appropriateenergy for application in, for example, efficient solar photovoltaics.We have developed a facile colloidal method for the synthesis of size-controlled,homogeneous SnxGe1–xalloy nanocrystals (NCs) with remarkably high tinconcentration (xup to 0.42). We demonstrate thatNCs of the same size exhibit a pronounced, systematic red-shift inthe optical band gap, and a significant increase in molar absorptivity,with increasing Sn-content, and a measurable photoluminescence wasobserved from NCs with high contents. The indications of at leastpartial direct-gap character in these NCs, combined with their broadtunability throughout the infrared, suggest their promise for usein solution-processed solar cells. [ABSTRACT FROM AUTHOR]

The ever-growing need for energygeneration and storage applicationsdemands development of materials with high performance and long-termstability. A sizable number of chalcogenide-based materials have beeninvestigated for supercapacitor applications. Layer-structured chalcogenidesare advantageous in terms of providing large surface area with goodionic conductivity and ability to host a variety of atoms or ionsbetween the layers. CuSbS2is a ternary layered chalcogenidematerial that is composed of earth abundant and less-toxic elements.For the first time, we have developed a simple colloidal method forthe synthesis of CuSbSexS2–xmesocrystals over the whole composition range (0≤ x≤ 2) by substitution of S withSe. Our approach yields mesocrystals with belt-like morphology forall the compositions. X-ray diffraction results show that substitutionof sulfur with selenium in CuSbS2enables tuning the widthof the interlayer gap between the layers. To investigate the suitabilityof CuSbSexS2–xmesocrystals for supercapacitor applications, we have carriedout electrochemical measurements by cyclic voltammetry and galvanostaticcharge–discharge measurements in 3 M KOH, NaOH and LiOH electrolytes.Our investigations reveal that the mesocrystals exhibit promisingspecific capacitance values with excellent cyclic stability. The uniqueproperties of CuSbSexS2–xmesocrystals make them attractive both for solarenergy conversion and energy storage applications. [ABSTRACT FROM AUTHOR]

Triclosan is a common antimicrobial agent that is found in significant levels in the aquatic environment and may elicit effects on aquatic organisms through unexpected modes of action. In this study, triclosan was quantified in fish from the Kaveri River, India, by using the gas chromatography and mass spectrometry technique and it was found in the range of 0.73–50 ng/g wet weight (ww). The mean bioaccumulation factor based on water (BAFw820) and sediment (BAFs2.12) in the Kaveri River showed that triclosan is accumulative in fish, and reflects its feeding behavior. The bioaccumulation indicates triclosan's persistence or prevalence throughout the river stretch. Human risk assessment through dietary intake demonstrated that the triclosan exposure is five orders of magnitude lower than the acceptable daily intake (50 μg/kg bw) and US EPA reference dose (300 μg/kg bw/day). This investigation is the first to report the bioaccumulation of triclosan in freshwater fish from India. Further, the results indicate that this fish acts as a biomarker of exposure for triclosan and thus shall be used to report triclosan pollution in the future. [ABSTRACT FROM AUTHOR]

Abstract: Dye sensitized solar cells are commonly fabricated using expensive platinum as a counter electrode material. We demonstrate for the first time the use of CuSbS2 as a replacement for platinum in dye sensitized solar cells. The performance of solar cells using CuSbS2 is found to be comparable with that using platinum counter electrode. [Copyright &y& Elsevier]

A wide variety of copper-based semiconductingchalcogenides havebeen investigated in recent years to address the need for sustainablesolar cell materials. An attractive class of materials consistingof nontoxic and earth abundant elements is the copper–antimony–sulfides.The copper–antimony–sulfide system consists of fourmajor phases, namely, CuSbS2(Chalcostibite), Cu12Sb4S13(Tetrahedrite), Cu3SbS3(Skinnerite), and Cu3SbS4(Fematinite).All four phases are p-type semiconductors having energy band gapsbetween 0.5 and 2 eV, with reported large absorption coefficient valuesover 105cm–1. We have for the firsttime developed facile colloidal hot-injection methods for the phase-puresynthesis of nanocrystals of all four phases. Cu12Sb4S13and Cu3SbS3are foundto have direct band gaps (1.6 and 1.4 eV, respectively), while theother two phases display indirect band gaps (1.1 and 1.2 eV for CuSbS2and Cu3SbS4, respectively). The synthesismethods yield nanocrystals with distinct morphology for the differentphases. CuSbS2is synthesized as nanoplates, and Cu12Sb4S13is isolated as hollow structures,while uniform spherical Cu3SbS3and oblate spheroidnanocrystals of Cu3SbS4are obtained. In orderto understand the optical and electrical properties, we have calculatedthe electronic structures of all four phases using the hybrid functionalmethod (HSE 06) and PBE generalized gradient approximation to densityfunctional theory. Consistent with experimental results, the calculationsindicate that CuSbS2and Cu3SbS4areindirect band gap materials but with somewhat higher band gap valuesof 1.6 and 2.5 eV, respectively. Similarly, Cu3SbS3is determined to be a direct band gap material with a gapof 1.5 eV. Interestingly, both PBE and HSE06 methods predict metallicbehavior in fully stoichiometric Cu12Sb4S13phase, with opening up of bands leading to semiconductingor insulating behavior for off-stoichiometric compositions with avarying number of valence electrons. The absorption coefficient valuesat visible wavelengths for all the phases are estimated to range between104and 105cm–1, confirmingtheir potential for solar energy conversion applications. [ABSTRACT FROM AUTHOR]

Layered materials with controlled thickness down to monolayer are being intensively investigated for unraveling and harnessing their dimension-dependent properties. Copper antimony sulfide (CuSbS2) is a ternary layered semiconductor material that has been considered as an absorber material in thin film solar cells due to its optimal band gap (~1.5 eV) with high absorption coefficient of over >104 cm-1. We have for the first time developed solution-based approaches for the synthesis of mono-, few-, and multiple layers of CuSbS2. These include a colloidal bottom-up approach for the synthesis of CuSbS2 nanoplates with thicknesses from six layers to several layers, and a hybrid bottom-up-top-down approach for the formation of CuSbS2 mesobelts. The latter can be exfoliated by Li-ion intercalation and sonication to obtain layers down to monolayer thickness. Time-dependent TEM studies provide important insights into the growth mechanism of mesobelts. At the initial stage the nanoplates grow laterally to form nanosheets as the primary structure, followed by their folding and attachment through homoepitaxy to form prolate-like secondary structures. Eventually, these prolate-like structures form mesocrystals by oriented attachment crystal growth. The changes in optical properties with layer thickness down to monolayers have been studied. In order to understand the thickness-dependent optical and electrical properties, we have calculated the electronic structures of mono- and multiple layers (bulk) of CuSbS2 using the hybrid functional method (HSE 06). We find that the monolayers exhibit noticeably different properties from the multilayered or the bulk system, with a markedly increased band gap that is, however, compromised by the presence of localized surface states. These localized states are predominantly composed of energetically favorable Sb pz states, which break off from the rest of the Sb p states that would otherwise be at the top of the gap. The developed solution-based synthesis approaches are versatile and can likely be extended to other complex layered sulfides. [ABSTRACT FROM AUTHOR]

Spin-based transport in semiconductorsystems has been proposedas the foundation of a new class of spintronic devices. For the practicalrealization of such devices, it is important to identify new magneticsystems operating at room temperature that can be readily integratedwith standard semiconductors. A promising class of materials for thispurpose is magnetic chromium-based chalcogenides that have the spinelstructure. Nanocrystals of CoxCu1–xCr2S4have been synthesizedover the entire composition range by a facile solution-based method.While CuCr2S4is a ferromagnetic metal, CoCr2S4is known to be a ferrimagnetic semiconductor.Systematic changes in the lattice parameter, size, and magnetic propertiesof the nanocrystals are observed with composition. The nanocrystalsare magnetic over the entire range, with a decrease in the magnetictransition temperature with increasing Co content. Band structurecalculations have been carried out to determine the electronic andmagnetic structure as a function of composition. The results suggestthat ferrimagnetic alignment of the Co and Cr moments results in adecrease in magnetization with increasing Co concentration. [ABSTRACT FROM AUTHOR]

Recent advances in nanotechnology could facilitate the productionof cheaper solar cells. This review describes synthetic routes tovarious nanostructured materials that are potentially useful in photovoltaicapplications. We have focused on materials that are based on earthabundant elements and/or those that are held to have lower toxicity.Methods to synthesize binary chalcogenides with variable stoichiometriessuch as iron sulfide, copper sulfide, and nickel sulfide are describedin detail. Other important photovoltaic materials such as cadmiumtelluride and lead sulfide are also covered. Methods to prepare emergingmaterials such as tin sulfide and bismuth sulfide are also discussed.Finally routes to ternary materials, e.g. copper indium sulfide and/orselenide and the quaternary material copper zinc tin sulfide, arediscussed. [ABSTRACT FROM AUTHOR]

Abstract: Ultra-thin (<1.0nm) nanorods or nanowires of β-In2S3were synthesized from the thermolysis of the indium(III) complex of 1,1,5,5-tetra-iso-propyl-2-thiobiuret in hot oleylamine. [Copyright &y& Elsevier]

A series of diorganotin complexes of dithiocarbamates[Sn(C4H9)2(S2CN(RR′)2)2] (R, R′ = ethyl (1); R =methyl, R′ = butyl (2); R, R′ = butyl (3); R = methyl, R′ = hexyl (4); and [Sn(C6H5)2(S2CN(RR′)2)2] (R, R′ = ethyl (5); R =methyl, R′ = butyl (6); R, R′ = butyl (7); R = methyl, R′ = hexyl (8) were synthesized.Single-crystal X-ray structures of 2, 3,and 8were determined. Thermogravimetric analysis (TGA)showed single-step decomposition for the complexes 1, 3, and 5–8, and double-stepdecomposition for the complexes 2and 4between195 °C and 325 °C. Complexes 1–4were used as single-source precursors for the depositionof SnS thin films by aerosol-assisted chemical vapor deposition (AACVD)at temperatures from 400 °C to 530 °C. Orthorhombic SnSthin films were deposited from all four complexes at all depositiontemperatures. The films were characterized by UV–vis spectroscopy,powder X-ray diffraction (p-XRD), Raman spectroscopy, scanning electronmicroscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), andalso electrical resistivity measurements. [ABSTRACT FROM AUTHOR]

The response of the tumour microenvironment to anti-cancer drugs can influence treatment efficacy. Current drug-screening methodologies fail to distinguish and quantify simultaneously the concomitant effect of drugs on the tumour stroma and cancer cells. To overcome this limitation we have developed a fluorescence-based experimental model that employs m Cherry-labelled stromal cells (e.g. bone marrow fibroblastic stromal cells) co-cultured in direct contact with enhanced green fluorescent protein-labelled tumour cell lines for accurate assessment of proliferation and viability in both cell compartments and adhesion of tumour cells. Additionally, we used fluorescence-based image analysis to determine morphological changes that correlate with cell function (e.g. morphology of the actin cytoskeleton and nuclearity of osteoclasts to predict their bone resorption activity). Using this platform we have revealed that dexamethasone induces HS5 fibroblast proliferation and contact with multiple myeloma cells via a process involving Src/c- Abl kinases. Osteoclasts also inhibited dexamethasone-induced apoptosis in myeloma cells while retaining their normal morphology and functionality in bone resorption. Myeloma resistance to dexamethasone mediated by HS5 cells and osteoclasts was reversed by treatment with the Src/c- Abl inhibitor dasatinib but not with bortezomib. This new experimental platform provides a more precise screening of new therapeutics for improved efficacy of tumour cell killing within the bone marrow microenvironment. [ABSTRACT FROM AUTHOR]

Nanocrystals and nanoclusters of the room-temperature magnetic spinel CuCr2S4 have been synthesized using a facile solution-based method. The synthesis involves hot injection of an excess of 1-dodecanethiol (1-DDT) into a boiling coordinating solvent containing CuCl2 and CrCl3·6H2 O. Using octadecylamine (ODA) as a solvent yields cube-shaped nanocrystals with an average size of 20 ± 2 nm, while with oleylamine (OLA), nanoclusters with an average size of 31 ± 2.5 nm are obtained. In both cases, powder X-ray diffraction patterns confirmed the formation of the pure spinel phase without any impurities. While the synthesized powders are superparamagnetic near room temperature, they exhibit ferromagnetic behavior at lower temperatures, with magnetization (Ms) values of 30 emu/g (1.63 μB/f.u.) and 33 emu/g (1.79 μB/f.u.) for the ODA- and OLA-capped nanocrystals and nanoclusters, respectively, at 5 K. [ABSTRACT FROM AUTHOR]

Cobalt(II)/Nickel(II) complexes of 4-thiopent-3-ene-2-thione (SacSac), [M(SacSac)2](M = Co, Ni) have been used as single source precursors (SSPs) for the preparation of cobalt/nickel sulfide thin films by aerosol-assisted chemical vapor deposition (AACVD). Cobalt or nickel sulfide nanoparticles were grown by thermal decomposition of the precursor in hot trioctylphosphine oxide (TOPO) or hexadecylamine (HDA). XRD analysis showed that all samples of cobalt or nickel sulfide are of the sulfur deficient phases (Ni9S8, Co9S8, Ni7S6, or Ni3S2). SEM and TEM analysis showed that nickel sulfide formed nanowires, nanorods and spheres; cobalt sulfide formed plate like structures and spheres. The chemical compositions of the nanoparticles can be controlled by varying temperature or the capping agents. [ABSTRACT FROM AUTHOR]

The iron(III) complexes of several 1,1,5,5-tetraalkyl-2-thiobiurets [Fe(SON(CNiPr2)2)3 (1), Fe2(μ-OMe)2(SON(CNEt2)2)2 (2), Fe(SON(CNEt2)2)3 (3). and Fe(SON(CNMe2)2)3 (4)] have been synthesized, and the single-crystal X-ray structures of 1,2, and 4 have been determined. The magnetic properties of complex 2 as a function of the temperature and field were studied. Thermogravimetric analysis of complexes 1-4 showed the decomposition in one major step to iron sulfide residues. All fourcomplexes were used as single-source precursors for the deposition of iron sulfide thin films by aerosol-assisted chemical vapor deposition. Complex 1 gave hexagonal troilite FeS films with a small amount of tetragonal pyrrhotites Fe1-xS at 300 °C, whereas only troilite FeS was deposited at 350,400, or 450 °C. Complexes 2 and 3 deposited a mixture of hexagonal troilite FeS and cubic pyrite FeS2 films at all temperatures. Complex 4 deposited very thin films of FeS at all temperatures as troilite. Scanning electron microscopy images of the films deposited from all complexes showed that the morphology consisted of plates, granules, rods, and sheets like crystallites. The size and shapes of these crystallites were dependent on the growth temperature and the precursor used. This is the first time that iron(III) thiobiuret complexes have been used as single-source precursors for iron sulfide thin films. [ABSTRACT FROM AUTHOR]

A series of new metal complexes of thiobiurets and dithiobiurets have been synthesized and characterized. The compounds are potentially useful as novel single source precursors for the deposition of metal sulfide thin films or nanoparticles. [ABSTRACT FROM AUTHOR]

A facile method for the preparation of dimorpholides of dithioacetylacetonate is described together with a X-ray single crystal structure of the ligand and of [Cd(msacmsac)2(NO3)2] (msacmsac = dimorpholinodithioacetylacetonate). The cadmium complex has been used as a single source precursor for the deposition of the CdS thin films by the aerosol assisted chemical vapour deposition (AACVD) method or as nanorods by thermolysis in oleylamine. The thin films and nanorods were characterized by electronic spectra (UV-Vis), photoluminescence (PL), X-ray diffraction (XRD), selected area electron diffraction (SAED), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). To the best of our knowledge [Cd(msacmsac)2(NO3)2] is the first complex in its class to be used as a single source precursor to deposit CdS thin films or nanoparticles. [ABSTRACT FROM AUTHOR]

Although myeloid sarcomas (MS) are frequently associated with acute myeloid leukaemia (AML), the occurrence of mediastinal MS is a much rarer event. The authors describe a distinct group of three AML patients with mediastinal MS and complex cytogenetics presenting at their centre over a 7-year period. Clinical features consistent with superior vena caval obstruction were noted at presentation in two of the three patients. Mediastinal mass was detected on routine chest radiography, and biopsies confirmed the diagnosis of MS. One patient relapsed after consolidation chemotherapy and died from progressive disease. Two patients underwent allogeneic haemopoietic stem cell transplant, but succumbed to transplant related complications. Review of mediastinal MS over the last 20 years shows that a significant proportion of patients have complex cytogenetic abnormalities and a poor long-term prognosis. Early and accurate diagnosis is essential and patients should be managed along the lines of high risk AML. [ABSTRACT FROM AUTHOR]

The article focuses on combination therapy of rituximab and thalidomide for multiple castleman disease (MCD), similar to lymphoma. 11 patients with MCD were given rituximab and thalidomide combination therapy during a study followed by thalidomide. The combination therapy induced durable and significant outcomes in majority of the patients without the need for exposure to chemotherapy.

The article discusses the effectiveness of bendamustine, thalidomide, and dexamethasone as therapy for myeloma patients with end stage renal disease. It states that myeloma patients experience renal impairment which needs to be treated by a combination of drugs that are clinically proven for their effectiveness. It discusses clinical trials, myeloma, and renal failure.

Real-world data on regimens for relapsed/refractory multiple myeloma (RRMM) represent an important component of therapeutic decision-making. This multi-centric, retrospective, observational study conducted by the treating physicians evaluated the effectiveness and safety of ixazomib-lenalidomide-dexamethasone (IRd) in 155 patients who received ixazomib via early access programs in Greece, the UK, and the Czech Republic. Median age was 68 years; 17% had an Eastern Cooperative Oncology Group performance status ≥ 2; median number of prior therapies was 1 (range 1-7); 91%, 47%, and 17% had received prior bortezomib, thalidomide, and lenalidomide, respectively. Median duration of exposure to ixazomib was 9.6 months. Overall response rate was 74%, including 35% very good partial response or better (16% complete response). Median progression-free survival (PFS) was 27.6 months (27.6 and 19.9 months in patients with 1 or > 1 prior lines, respectively). IRd treatment for ≥ 6 months was associated with longer PFS (hazard ratio 0.06). Fourteen patients (9%) discontinued IRd due to adverse events/toxicity in the absence of disease progression. Peripheral neuropathy was reported in 35% of patients (3% grades 3-4). These findings support the results of the phase III TOURMALINE-MM1 trial in a broader real-world RRMM population. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) and its precursor states, smoldering myeloma (SM) and monoclonal gammopathy of undetermined significance (MGUS) are associated with increased incidence of thrombosis, however the cause of this is unknown. Lenalidomide treatment of MM substantially improves patient survival, although significantly increases thrombotic risk by an unknown mechanism. This pilot study aimed to establish the impact of MM and its treatment with Lenalidomide on platelet function. We analyzed platelet function in MGUS, SM and MM compared to healthy controls. We report an increase in platelet reactivity in MGUS, SM, and MM where increases in fibrinogen binding, P-selectin exposure, altered receptor expression, elevated levels of aggregation and enhanced sensitivity to agonist stimulation were observed. We also demonstrate an increase in patient platelet reactivity post Lenalidomide treatment compared to pre-treatment. We show Lenalidomide treatment of platelets ex vivo increased reactivity that was associated with formation of larger thrombi at arterial shear rates but not venous shear rates. This study demonstrates a clear increase in platelet reactivity and prothrombotic potential in patients with MGUS, SM and MM which is elevated further upon treatment with Lenalidomide. Our observations suggest that more detailed studies are warranted to determine mechanisms of thrombotic complications to enable the development of new preventative strategies that specifically target platelets. [ABSTRACT FROM AUTHOR]

• Mass spectrometry has an advantage over serum protein electrophoresis at screening. • Additional monoclonal proteins seen by mass spectrometry may be clinically relevant. • Higher sensitivity when screening for monoclonal gammopathies has clinical utility. • Mass spectrometry should be investigated at all stages of monoclonal gammopathies. Mass spectrometry has recently been proposed as a novel sensitive screening tool for monoclonal gammopathies. In a small study we have tested the ability of quantitative immunoprecipitation mass spectrometry (QIP-MS) to identify low level monoclonal immunoglobulins not currently detected by the initial serum protein electrophoresis (SPEP) screen. QIP-MS positively identified the primary monoclonal immunoglobulins in all 11 patient samples alongside additional monoclonal immunoglobulins in a subset of patient samples. We conclude that QIP-MS has clinical utility as a first-line screening tool for monoclonal gammopathy investigation, identifying monoclonality in patients with higher sensitivity and resolution compared to the current standard methods. [ABSTRACT FROM AUTHOR]

This article presents a study on successful pregnancies involving men with chronic myeloid leukemia on imatinib therapy. Imatinib has been discovered to inhibit potently other tyrosine kinases. In addition, there have also been reports of spontaneous abortion and meningocoele, highlighting potential risks of conception while undergoing imatinib therapy.

Nanocrystals of all four phases of the Cu-Sb-S system are prepared by a colloidal hot-injection method. [ABSTRACT FROM AUTHOR]

Nanocrystals of CoxCu1-xCr2S4 are prepared over the entire composition range by reaction of appropriate amounts of CuCl2, CoCl2, and CrCl3 in the presence of octadecylamine (360 °C, N2 atmosphere) followed by injection of 1-dodecanethiol and further heating for 1 h. [ABSTRACT FROM AUTHOR]

Review: 238 refs. [ABSTRACT FROM AUTHOR]

Daratumumab is the first anti-CD38 targeting monoclonal antibody approved as monotherapy in multiply relapsed myeloma patients who progressed following prior treatment with proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs). We present real world data on the efficacy of single agent daratumumab in a cohort of 55 multiply relapsed patients treated in the UK. The median age was 72 years, the majority (96%) received ≥ 3 previous lines of treatment; 54.5% were PI-refractory, 76.4% were IMiD-refractory and 47.2% were double refractory; 20% of patients had high-risk (HR) disease. The overall response rate was 49%. After a median follow up of 9.2 months, the median progression-free survival (PFS) for the total cohort was 5.1 months. Patients who achieved a partial response or better (≥PR) demonstrated a significantly longer PFS compared to those with

Simple Summary: The activation of osteoclasts occurs in up to 80% of myeloma patients. Osteoclasts promote myeloma resistance to therapeutic treatments and the formation of bone lytic lesions, resulting in bone pain and fractures in patients. However, the role of osteoclasts in drug resistance is generally overseen when performing preclinical screenings to identify new therapeutics for multiple myeloma. We propose in our study a new methodology, scalable to high throughput for the analysis of drug efficacy to better predict efficacy in myeloma patients that develop bone disease. We have identified GDC-0941 as a drug candidate that, used in combination treatments, could enhance the efficacy of currently used therapeutic drugs for myeloma by overcoming resistance mediated by osteoclasts, as well as bone marrow mesenchymal/fibroblastic stromal cells. Our work supports exploring GDC-0941 in combination with current clinical drugs for myeloma patients with active bone disease. Osteoclasts contribute to bone marrow (BM)-mediated drug resistance in multiple myeloma (MM) by providing cytoprotective cues. Additionally, 80% of patients develop osteolytic lesions, which is a major cause of morbidity in MM. Although targeting osteoclast function is critical to improve MM therapies, pre-clinical studies rarely consider overcoming osteoclast-mediated cytoprotection within the selection criteria of drug candidates. We have performed a drug screening and identified PI3K as a key regulator of a signalling node associated with resistance to dexamethasone lenalidomide, pomalidomide, and bortezomib mediated by osteoclasts and BM fibroblastic stromal cells, which was blocked by the pan-PI3K Class IA inhibitor GDC-0941. Additionally, GDC-0941 repressed the maturation of osteoclasts derived from MM patients and disrupted the organisation of the F-actin cytoskeleton in sealing zones required for bone degradation, correlating with decreased bone resorption by osteoclasts. In vivo, GDC-0941 improved the efficacy of dexamethasone against MM in the syngeneic GFP-5T33/C57-Rawji mouse model. Taken together, our results indicate that GDC-0941 in combination with currently used therapeutic agents could effectively kill MM cells in the presence of the cytoprotective BM microenvironment while inhibiting bone resorption by osteoclasts. These data support investigating GDC-0941 in combination with currently used therapeutic drugs for MM patients with active bone disease. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) and its precursor states, smoldering myeloma (SM) and monoclonal gammopathy of undetermined significance (MGUS) are associated with increased incidence of thrombosis, however the cause of this is unknown. Lenalidomide treatment of MM substantially improves patient survival, although significantly increases thrombotic risk by an unknown mechanism. This pilot study aimed to establish the impact of MM and its treatment with Lenalidomide on platelet function. We analyzed platelet function in MGUS, SM and MM compared to healthy controls. We report an increase in platelet reactivity in MGUS, SM, and MM where increases in fibrinogen binding, P-selectin exposure, altered receptor expression, elevated levels of aggregation and enhanced sensitivity to agonist stimulation were observed. We also demonstrate an increase in patient platelet reactivity post Lenalidomide treatment compared to pre-treatment. We show Lenalidomide treatment of platelets ex vivo increased reactivity that was associated with formation of larger thrombi at arterial shear rates but not venous shear rates. This study demonstrates a clear increase in platelet reactivity and prothrombotic potential in patients with MGUS, SM and MM which is elevated further upon treatment with Lenalidomide. Our observations suggest that more detailed studies are warranted to determine mechanisms of thrombotic complications to enable the development of new preventative strategies that specifically target platelets. What is the context? Multiple myeloma is associated with increased risk of thrombosis, although the potential role of platelets in this has not been evaluated. What is new? We show in this pilot study that multiple myeloma and its precursor states of smoldering myeloma and monoclonal gammopathy of undetermined significance are associated with increased levels of platelet responses. This is further exacerbated by treatment with the immunomodulatory drug lenalidomide. What is the impact? This study suggests that more detailed studies are warranted to explore the mechanisms that cause these effects in a larger population of patients, since this may reveal new approaches to prevent myeloma-associated thrombotic complications [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the use of bendamustine, thalidomide, and dexamethasone for multiple myeloma patients.

Objectives: Daratumumab is the first anti-CD38 monoclonal antibody (Mab) used to treat myeloma in the newly diagnosed setting and in the relapsed setting. Isatuximab, another Mab targeting a specific epitope on the CD38 receptor, was recently approved in the UK in combination with pomalidomide and dexamethasone (IsaPomDex) to treat myeloma patients who received three prior lines of therapy. However, there is a lack of understanding of whether using a prior anti-CD38 Mab (e.g. daratumumab) can affect the efficacy of another Mab (e.g. isatuximab), when the latter is used to treat a subsequent relapse. Methods: We performed a UK-wide outcomes study of IsaPomDex in the real-world. In this case series, we report a detailed descriptive analysis of the characteristics and clinical outcomes of five IsaPomDex patients in UK routine practice (Patients I to V), with a prior exposure to daratumumab. Results: Age range was 51–77 years with two patients >70 and three patients <70 years. The cytogenetic risk was standard in two patients, high in two patients and not known in one patient. Prior daratumumab regimen were monotherapy (dara-mono) in one patient (II), and daratumumab with bortezomib and dexamethasone (DVd) in four patients. Responses to prior daratumumab were: very good partial response (VGPR) in two patients (I and III), minor response-stable disease (MR-SD) in one patient (II), and progressive disease (PD) in two patients (IV and V). Median (range) number of IsaPomDex cycles received was 2 (1–4). Outcomes of IsaPomDex were PD in three patients (II, IV and V) and a response in two patients. Response categories were: MR-SD in patient I and PR in patient III. Discussion: Despite the limitations of our case series, we described the first UK real-world report of IsaPomDex outcomes in myeloma patients with a prior exposure to daratumumab. Conclusion: Large prospective studies are required to further evaluate myeloma outcomes in this setting. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 63-year-old woman who is suffering from pain in her left thigh. She undergoes a bone marrow trephine biopsy which indicates infiltration of lymphoplasmacytic cells and huge plasma cells. It states that the plasma cells are stained positively with CD20, nuclear Cyclin D1 and lambda light chain and the patient was diagnosed with myeloma. It adds that the plasma cells are characterized with intracytoplasmic immunoglobulin inclusion (Mott cells).

Summary: Depth of response is the critical determinant of prognosis in amyloid light‐chain (AL) amyloidosis. Here, we aim to identify patients who are unlikely to improve response based on analysis of baseline characteristics and 1‐month response. In a multivariate model, difference in involved amyloidogenic and uninvolved serum free light chains (dFLC) at diagnosis (dFLC >400 mg/l, odds ratio [OR] 4.051, p < 0.005) and no response at 1 month (OR 4.787, p < 0.005) were significant predictors of no improvement in response. Only 5% of patients with a dFLC of >400 mg/l and no response at 1 month improved their response (p < 0.005). We suggest that these patients should switch treatment early, subject to their functional status. [ABSTRACT FROM AUTHOR]

The combination of panobinostat, bortezomib and dexamethasone (PanBorDex) is available as a treatment option for relapsed refractory multiple myeloma (RRMM) based on the PANORAMA-1 trial which investigated this triplet in early relapse. In routine clinical care, PanBorDex is used primarily in later relapses and is commonly administered in attenuated dosing schedules to mitigate the treatment-related toxicity. We set out to evaluate efficacy and safety outcomes with PanBorDex later in the disease course and evaluate the role of attenuated dosing schedules. This was a retrospective evaluation of patients treated in routine clinical practice between 2016–2019 across seven heamatology centres in the UK; patients who received at least one dose of PanBorDex were eligible for inclusion. The dosing schedule of panobinostat (10mg, 15mg or 20mg, twice or three times a week) and bortezomib (0.7mg/m2, 1mg/m2 or 1.3mg/m2 once or twice weekly) was as per treating physician choice. Patients received treatment until disease progression or unacceptable toxicity. The primary outcome is response rates according to IMWG criteria. Key secondary endpoints include progression-free survival (PFS) and overall survival (OS). Other secondary endpoints include rates of adverse events according to CTCAE criteria. In total, 61 patients were eligible for inclusion and received PanBorDex primarily as ≥5th line of treatment. One third of patients received PanBorDex at full dose, for the remaining two thirds, treatment was given in reduced dose intensities. The overall response rate was 44.2%, including 14.7% very good partial response (VGPR) rates; 68.8% of patients derived clinical benefit with stable disease or better. The median PFS was 3.4 months; non-refractory patients and those who achieved VGPR benefited from prolonged PFS of 11.4 months and 17.7 months, respectively. The median OS was 9.5 months. The triplet was associated with 45% and 18% incidence of grade 3–4 thrombocytopenia and diarrhea, respectively. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) remains an incurable malignancy. Approximately 37% of patients with plasma cell myeloma are over the age of 75 and the median age of diagnosis is 70. The management approach to over 70s differs from younger patients, as treatment goals may vary and underlying co-morbidities and expected treatment related toxicities have to be taken into account. Individualisation of management is important, aiming to achieve the best response whilst minimising adverse events. A proportion of patients will be unable to tolerate any treatment with palliation being appropriate. Age alone should not be a barrier to treatment however, with some fit patients over the age of 70 potentially benefitting from intensive treatment options including high dose chemotherapy with autologous stem cell rescue. Comprehensive geriatric assessment is indicated in the over 70s; this should be employable in a clinic outpatient setting to make it feasible. Outcomes of this assessment potentially help physicians’ choice of therapy. For decades the combination of Melphalan and prednisolone was the standard of care for older MM patients. Over the last ten years, newer drugs and combinations have improved therapeutic options for patients but are yet to demonstrate vast improvement in overall survival in this cohort. [ABSTRACT FROM AUTHOR]

In the last decade, the introduction of the serum-free light-chain (sFLC) assay has been an important advance in the diagnosis and management of plasma cell dyscrasias, particularly monoclonal light-chain diseases. The immunoassay was developed to detect free light chains in serum by using anti-FLC antibodies which specifically recognised epitopes on light chains that were ‘hidden’ in intact immunoglobulins. Since its introduction in 2001, there have been several publications in the English language literature discussing the clinical utility as well as analytical limitations of the sFLC assay. These studies have highlighted both positive and negative aspects of the assay particularly with regard to its sensitivity and specificity and the technical challenges that can affect its performance. The contribution and significance of the sFLC assay in the management of light-chain myeloma, primary amyloid light-chain (AL) amyloidosis and non-secretory myeloma are well recognised and will be addressed in this review. The aim of this article is to also review the published literature with a view to providing a clear understanding of its utility and limitations in the diagnosis, prognosis and monitoring of plasma dyscrasias including intact immunoglobulin multiple myeloma (MM) and monoclonal gammopathy of unknown significance (MGUS). The increasing interest in using this assay in other haematological conditions will also be briefly discussed. [ABSTRACT FROM AUTHOR]

Highlights: [•] HDA and OA capped Bi2Se3 and Bi2Te3 nanoparticles have been synthesized by a solution based method. [•] The reaction temperature determined whether the Bi2Se3 were spherical of faceted in shape. [•] Spherical Bi2Te3 nanocrystals were obtained at all temperatures. [Copyright &y& Elsevier]