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Patients with newly diagnosed multiple myeloma and high-risk cytogenetic abnormalities (HRCA) represent an unmet medical need. In the FORTE trial, lenalidomide and dexamethasone plus carfilzomib (KRd) induction resulted in a higher proportion of patients with at least a very good partial response as compared with carfilzomib, cyclophosphamide, and dexamethasone (KCd), and carfilzomib plus lenalidomide maintenance prolonged progression-free survival compared with lenalidomide maintenance. In this prespecified analysis of the FORTE trial, we described the outcomes of enrolled patients according to their cytogenetic risk. The UNITO-MM-01/FORTE was a randomised, open-label, phase 2 trial done at 42 Italian academic and community practice centres, which enrolled transplant-eligible patients with newly diagnosed multiple myeloma aged 18–65 years. Eligible patients had newly diagnosed multiple myeloma based on standard International Myeloma Working Group criteria, a Karnofsky performance status of at least 60%, and had not received any previous treatment with anti-myeloma therapy. At enrolment, patients were stratified according to International Staging System stage (I vs II/III) and age (<60 years vs 60–65 years) and randomly assigned (1:1:1) to KRd plus autologous stem-cell transplantation (ASCT; four 28-day induction cycles with KRd, melphalan at 200 mg/m2 and ASCT [MEL200-ASCT], followed by four 28-day KRd consolidation cycles), 12 28-day KRd cycles, or KCd plus ASCT (four 28-day induction cycles with KCd, MEL200-ASCT, and four 28-day KCd consolidation cycles), using a web-based system (block randomisation, block size of 12). Carfilzomib was administered at 20 mg/m2 on days 1 and 2 of cycle 1, followed by 36 mg/m2 intravenously administered on days 8, 9, 15, and 16 of cycle 1, and then 36 mg/m2 intravenously administered for all subsequent doses on days 1, 2, 8, 9, 15, 16; lenalidomide 25 mg was administered orally on days 1–21; cyclophosphamide 300 mg/m2 was administered orally on days 1, 8, and 15; and dexamethasone 20 mg was administered orally or intravenously on days 1, 2, 8, 9, 15, 16, 22, and 23. After the consolidation phase, patients were stratified according to induction–consolidation treatment and randomly assigned (1:1; block size of 8) to maintenance treatment with carfilzomib plus lenalidomide or lenalidomide alone. Carfilzomib 36 mg/m2 was administered intravenously on days 1–2 and days 15–16, every 28 days for up to 2 years, and lenalidomide 10 mg was administered orally on days 1–21 every 28 days until progression or intolerance in both groups. The primary endpoints were the proportion of patients with at least a very good partial response after induction with KRd versus KCd and progression-free survival with carfilzomib plus lenalidomide versus lenalidomide alone as maintenance treatment. In this preplanned analysis, we included patients enrolled in the FORTE trial with complete cytogenetic data on del(17p), t(4;14), t(14;16), del(1p), gain(1q) (3 copies), and amp(1q) (≥4 copies) assessed by fluorescence in-situ hybridisation analysis on CD138-positive sorted cells. We assessed progression-free survival, overall survival, minimal residual disease negativity, and 1-year sustained minimal residual disease negativity according to the presence of zero, one, and two or more HRCA across treatment groups. The FORTE trial is ongoing, and registered with ClinicalTrials.gov , NCT02203643. Between Feb 23, 2015, and April 5, 2017, 477 patients were enrolled, of whom 396 (83%) had complete cytogenetic data and were analysed (176 [44%] of whom were women and 220 [56%] were men). The median follow-up from first randomisation was 51 months (IQR 46–56). 4-year progression-free survival was 71% (95% CI 64–78) in patients with zero HRCA, 60% (95% CI 52–69) in patients with one HRCA, and 39% (95% CI 30–50) in patients with two or more HRCA. Compared with patients with zero HRCA, the risk of progression or death was similar in patients with one HRCA (hazard ratio [HR] 1·33 [95% CI 0·90–1·97]; p=0·15) and higher in patients with two or more HRCA (HR 2·56 [95% CI 1·74–3·75]); p<0·0001) across the induction–intensification–consolidation groups. Moreover, the risk of progression or death was also higher in patients with two or more HRCA versus those with one HRCA (HR 1·92 [95% CI 1·34–2·76]; p=0·0004). 4-year overall survival from the first randomisation was 94% (95% CI 91–98) in patients with zero HRCA, 83% (95% CI 76–90) in patients with one HRCA, and 63% (95% CI 54–74) in patients with two or more HRCA. Compared with patients with zero HRCA, the risk of death was significantly higher in patients with one HRCA (HR 2·55 [95% CI 1·22–5·36]; p=0·013) and two or more HRCA (HR 6·53 [95% CI 3·24–13·18]; p<0·0001). Patients with two or more HRCA also had a significantly higher risk of death than those with one HRCA (HR 2·56 [95% CI 1·53–4·28]; p=0·0004). The rates of 1-year sustained minimal residual disease negativity were similar in patients with zero HRCA (53 [35%] of 153] and with one HRCA (57 [41%] of 138) and were lower in patients with two or more HRCA (25 [24%] of 105). The median duration of follow-up from second randomisation was 37 months (IQR 33–42). 3-year progression-free survival from the second randomisation was 80% (95% CI 74–88) in patients with zero HRCA, 68% (95% CI 59–78) in patients with one HRCA, and 53% (95% CI 42–67) in patients with two or more HRCA. The risk of progression or death was higher in patients with one HRCA (HR 1·68 [95% CI 1·01–2·80]; p=0·048) and two or more HRCA (2·74 [95% CI 1·60–4·69], p=0·0003) than in patients with zero HRCA. This preplanned analysis of the FORTE trial showed that carfilzomib-based induction–intensification–consolidation regimens are effective strategies in patients with standard risk (zero HRCA) and high-risk (one HRCA) myeloma, resulting in similar rates of progression-free survival and 1-year sustained minimal residual disease negativity. Despite promising progression-free survival, patients with ultra-high-risk disease (those with 2 or more HRCA) still have an increased risk of progression and death and therefore represent an unmet medical need. Amgen and Celgene/Bristol Myers Squibb. [ABSTRACT FROM AUTHOR]

Background: Bortezomib-based induction followed by high-dose melphalan (200 mg/m2) and autologous stem-cell transplantation (MEL200-ASCT) and maintenance treatment with lenalidomide alone is the current standard of care for young and fit patients with newly diagnosed multiple myeloma. We aimed to evaluate the efficacy and safety of different carfilzomib-based induction and consolidation approaches with or without transplantation and of maintenance treatment with carfilzomib plus lenalidomide versus lenalidomide alone in newly diagnosed multiple myeloma.Methods: UNITO-MM-01/FORTE was a randomised, open-label, phase 2 trial done in 42 Italian academic and community practice centres. We enrolled transplant-eligible patients with newly diagnosed multiple myeloma aged 65 years or younger with a Karnofsky Performance Status of 60% or higher. Patients were stratified according to International Staging System stage (I vs II/III) and age (<60 years vs 60-65 years) and randomly assigned (1:1:1) to KRd plus ASCT (four 28-day induction cycles with carfilzomib plus lenalidomide plus dexamethasone [KRd], melphalan at 200 mg/m2 and autologous stem-cell transplantation [MEL200-ASCT], followed by four 28-day KRd consolidation cycles), KRd12 (12 28-day KRd cycles), or KCd plus ASCT (four 28-day induction cycles with carfilzomib plus cyclophosphamide plus dexamethasone [KCd], MEL200-ASCT, and four 28-day KCd consolidation cycles). Carfilzomib 36 mg/m2 was administered intravenously on days 1, 2, 8, 9, 15, and 16; lenalidomide 25 mg administered orally on days 1-21; cyclophosphamide 300 mg/m2 administered orally on days 1, 8, and 15; and dexamethasone 20 mg administered orally or intravenously on days 1, 2, 8, 9, 15, 16, 22, and 23. Thereafter, patients were stratified according to induction-consolidation treatment and randomly assigned (1:1) to maintenance treatment with carfilzomib plus lenalidomide or lenalidomide alone. Carfilzomib 36 mg/m2 was administered intravenously on days 1-2 and 15-16 every 28 days for up to 2 years; lenalidomide 10 mg was administered orally on days 1-21 every 28 days until progression or intolerance in both groups. The primary endpoints were the proportion of patients with at least a very good partial response after induction with KRd versus KCd and progression-free survival with carfilzomib plus lenalidomide versus lenalidomide alone as maintenance treatment, both assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02203643. Study recruitment is complete, and all patients are in the follow-up or maintenance phases.Findings: Between Feb 23, 2015, and April 5, 2017, 474 patients were randomly assigned to one of the induction-intensification-consolidation groups (158 to KRd plus ASCT, 157 to KRd12, and 159 to KCd plus ASCT). The median duration of follow-up was 50·9 months (IQR 45·7-55·3) from the first randomisation. 222 (70%) of 315 patients in the KRd group and 84 (53%) of 159 patients in the KCd group had at least a very good partial response after induction (OR 2·14, 95% CI 1·44-3·19, p=0·0002). 356 patients were randomly assigned to maintenance treatment with carfilzomib plus lenalidomide (n=178) or lenalidomide alone (n=178). The median duration of follow-up was 37·3 months (IQR 32·9-41·9) from the second randomisation. 3-year progression-free survival was 75% (95% CI 68-82) with carfilzomib plus lenalidomide versus 65% (58-72) with lenalidomide alone (hazard ratio [HR] 0·64 [95% CI 0·44-0·94], p=0·023). During induction and consolidation, the most common grade 3-4 adverse events were neutropenia (21 [13%] of 158 patients in the KRd plus ASCT group vs 15 [10%] of 156 in the KRd12 group vs 18 [11%] of 159 in the KCd plus ASCT group); dermatological toxicity (nine [6%] vs 12 [8%] vs one [1%]); and hepatic toxicity (13 [8%] vs 12 [8%] vs none). Treatment-related serious adverse events were reported in 18 (11%) of 158 patients in the KRd-ASCT group, 29 (19%) of 156 in the KRd12 group, and 17 (11%) of 159 in the KCd plus ASCT group; the most common serious adverse event was pneumonia, in seven (4%) of 158, four (3%) of 156, and five (3%) of 159 patients. Treatment-emergent deaths were reported in two (1%) of 158 patients in the KRd plus ASCT group, two (1%) of 156 in the KRd12 group, and three (2%) of 159 in the KCd plus ASCT group. During maintenance, the most common grade 3-4 adverse events were neutropenia (35 [20%] of 173 patients on carfilzomib plus lenalidomide vs 41 [23%] of 177 patients on lenalidomide alone); infections (eight [5%] vs 13 [7%]); and vascular events (12 [7%] vs one [1%]). Treatment-related serious adverse events were reported in 24 (14%) of 173 patients on carfilzomib plus lenalidomide versus 15 (8%) of 177 on lenalidomide alone; the most common serious adverse event was pneumonia, in six (3%) of 173 versus five (3%) of 177 patients. One patient died of a treatment-emergent adverse event in the carfilzomib plus lenalidomide group.Interpretation: Our data show that KRd plus ASCT showed superiority in terms of improved responses compared with the other two treatment approaches and support the prospective randomised evaluation of KRd plus ASCT versus standards of care (eg, daratumumab plus bortezomib plus thalidomide plus dexamethasone plus ASCT) in transplant-eligible patients with multiple myeloma. Carfilzomib plus lenalidomide as maintenance therapy also improved progression-free survival compared with the standard-of-care lenalidomide alone.Funding: Amgen, Celgene/Bristol Myers Squibb.Translation: For the Italian translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

This study introduces and validates an effective approach for monitoring the plasticizer amount and its concentration profile in polyvinyl chloride (PVC) formulations. The method combines gravimetric measurements with confocal Raman depth profiling analysis. Several flexible PVC (pPVC) formulations were compared in this study, including: pPVC@DEHP, using the monomeric plasticizer di(2-ethylhexyl) phthalate (DEHP); pPVC@PBA, using the polymeric plasticizer poly(butylene adipate) (PBA); and crosslinked pPVC (cPVC@DEHP), where isophorone diamine (IPDA) served as the crosslinker. Migration tests were performed according to UNI EN ISO 177 standard. Spectroscopic findings were correlated with gravimetric data, highlighting strong differences in the migration behavior among the formulations. The results demonstrate the effectiveness of the proposed method in quantifying plasticizer leaching and obtaining detailed concentration profiles at fine scale. [Display omitted] • A spectroscopic approach to monitor concentration profiles in plasticized PVC. • Cross-validation of the depth-profile analysis by gravimetric measurements. • The uptake kinetics is strongly influenced by plasticizer nature and PVC state. • Technologically relevant for plasticizer migration studies in coextruded PVC pipes. [ABSTRACT FROM AUTHOR]

Abstract The introduction of new therapeutic agents in multiple myeloma (MM), including proteasome inhibitors, immunoregulatory drugs and monoclonal antibodies, has improved the outcomes of patients, but in parallel has changed the frequency and epidemiology of infections. Hence, the great strides in the indications and use of new active treatments for MM need parallel progresses on the best approach to prophylaxis and supportive therapy for infections. Moving from the recognition that the above issue represents an unmet clinical need in MM, an expert panel assessed the scientific literature and composed a framework of recommendations for optimal infection control in patients candidate to active treatment for MM. The present publication represents a consensus document from questionnaires and consensus meetings held during 2017. The issues tackled in the project dealt with: infectious risk assessment, risk management and prophylaxis, intravenous immunoglobulin replacement therapy, antiviral and antibacterial vaccination. Considering the lack of conclusive and/or enough large studies for certain topics several recommendations derived from the personal experience of the experts. [ABSTRACT FROM AUTHOR]

Abstract The improvement in supportive care and the introduction of new therapeutic agents, including lenalidomide and hypomethylating agents, in myelodysplastic syndromes have improved patients' outcomes; however, at the same time, the frequency and epidemiology of infections have changed. Therefore, the great strides in the indications and use of new treatment strategies for myelodysplastic syndromes need a parallel progress in the best approach to prophylaxis and supportive therapy for infections. Based on the recognition that the above issues represent an unmet clinical need in myelodysplastic syndromes, an Italian expert panel performed a review of the literature and composed a framework of the best recommendations for optimal infection control in patient candidates to receive active treatment for myelodysplastic syndromes. In this consensus document we report the outcomes of that review and of the consensus meetings held during 2017. The issues tackled in the project dealt with: information to be collected from candidates for active treatment for myelodysplastic syndromes; how to monitor the risk of infection; antimicrobial prophylaxis; the role of iron chelation and antiviral/antibacterial vaccinations. For each of these issues, practice recommendations are provided. [ABSTRACT FROM AUTHOR]

Purpose The quantitative assessment of Positron Emission Tomography (PET) scans using standardized uptake value and derived parameters proved to be superior to traditional qualitative assessment in several retrospective or mono-centric prospective reports. Since different scanners give different quantitative readings, a program for clinical trial qualification (CTQ) is mandatory to guarantee a reliable and reproducible use of quantitative PET in prospective multi-centre clinical trials and in every-day clinical life. Methods We set up, under the auspices of Italian Foundation on Lymphoma (FIL), a CTQ program consisting of the PET/CT scan acquisition and analysis of 18 F and 68 Ge NEMA/IEC image quality phantoms for the reduction of inter-scanner variability. Variability was estimated on background activity concentration (BAC) and sphere to background ratio (SBR). Results The use of a 68 Ge phantom allowed reducing the inter-scanner variability among different scanners from 74.0% to 20.5% in BAC and from 63.3% to 17.4% in SBR compared to using the 18 F phantom. The CTQ criteria were fulfilled at first round in 100% and 28% of PET scanners with 68 Ge and 18 F respectively. Conclusions The 68 Ge phantom proved a reliable tool for PET scanner qualification, able to significantly reduce the potential sources of error while increasing the reproducibility of PET derived quantitative parameter measurement. [ABSTRACT FROM AUTHOR]

FMS-like tyrosine kinase 3 (FLT3) is one of the most closely studied genes in blood diseases. Numerous methods have been adopted for analyses, mainly in acute myeloid leukemia (AML) diagnostic work-up. According to international recommendations, the current gold standard approach allows FLT3 canonical mutations to be investigated, providing the main information for risk assessment and treatment choice. However, the technological improvements of the last decade have permitted "black side" gene exploration, revealing numerous hidden aspects of its role in leukemogenesis. The advent of the next-generation sequencing era emphasizes lights and shadows of FLT3 conventional mutational analysis, highlighting the need for a more comprehensive study of the gene. However, more extensive analysis is opening new, unexplored questions whose impact on clinical outcomes is still unknown. The present work is focused on the main topics regarding FLT3 mutational analysis in AML, debating the strengths and weaknesses of the current gold standard approach. The rights and wrongs of NGS introduction in clinical practice will be discussed, showing that a more extensive knowledge of FLT3 mutational status could lead to reconsidering its role in AML management. [ABSTRACT FROM AUTHOR]

Multi wall carbon nanotubes (MWCNTs) with different aspect ratios (30, 105 and 667) were included in a commercial fully biodegradable blend using melt mixing. Samples of composite systems prepared by hot molding and containing up to 1.2 vol% of MWCNTs were studied by means of DC electrical resistivity and dielectric spectroscopy in order to enhance effect of filler content and aspect ratio on their dielectric behavior. Raman spectroscopic investigations and morphological observations were also performed in order to correlate dielectric behavior with surface carbon nanotubes features and to check the actual level of dispersion of carbon nanotubes under the applied processing conditions. Results emphasized that the carbon nanotubes aspect ratio and their surface regularity determine the electrical properties of composites because they strongly influence percolation thresholds, dielectric permittivity and dissipation factor of produced materials. A satisfying dispersion of the filler seems to be achieved under the employed processing conditions. These preliminary results demonstrates possible applications of this type of biobased systems in many applications going from stress control to devices for high storage energy. [ABSTRACT FROM AUTHOR]

Abstract: The reaction of zinc oxide (ZnO) with stearic acid (StA) to form zinc stearate (ZnSt) has been investigated experimentally in a model matrix (unvulcanized styrene–butadiene rubber) by using confocal Raman microscopy and FTIR transmission spectroscopy. The heterogeneous nature of the reacting system has been confirmed. The Raman analysis has revealed the core–shell structure of the product, which is formed via the gradual shrinkage of the ZnO core and the concurrent formation of a surrounding ZnSt shell of increasing thickness. FTIR spectroscopy has provided information about the molecular state of aggregation of StA when dissolved in the rubber, as well as quantitative information on the reaction kinetics. The kinetic behaviour of the system has been interpreted using a semi-quantitative heterogeneous reaction model grounded on the Raman imaging results, which was able to catch the essential features of the phenomenon and to simulate reliably the experimental conversion vs time data at three different temperatures. [Copyright &y& Elsevier]

Abstract: The photo-oxidative stability of a bifunctional epoxy resin has been investigated and compared with that of the same resin additivated with a polyhedral oligomeric silsesquioxane (POSS) functionalized with epoxy groups. The study was aimed at a quantitative assessment of the stabilization effect of the POSS additive and at a deeper understanding of its origin through a detailed description of the photo-degradation process both in the pristine and in the POSS-containing resins. Fourier Transform infrared spectroscopy was employed for the kinetic and mechanistic analysis, and dynamic-mechanical spectroscopy to investigate the modifications of the molecular structure of the network. Scanning electron microscopy (SEM) was used for the characterization of the exposed surfaces, and fracture mechanics measurements to evaluate the fracture properties before and after photo-aging. In a homogeneous degradative regime (≅10 μm films) OG-POSS tends to enhance the sensitivity of the system toward photo-oxidation. On thicker samples (1.0 mm) the general deterioration of viscoelastic properties observed in the plain resin upon photo-degradation is almost completely suppressed with 20 wt% of the additive. A mechanism has been proposed to account for this effect, which was confirmed by SEM analysis of the degraded surfaces. [Copyright &y& Elsevier]

Abstract: Primary plasma cell leukemia (PPCL) is a rare and aggressive variant of multiple myeloma. This disease is associated with a very poor prognosis, and unfortunately it has not significantly improved during the last three decades. Autologous stem cell transplantation is generally recommended in eligible patients, but survival in transplanted PPCL patients is significantly lower than that of multiple myeloma. Recent preliminary data indicate that new drugs, in particular lenalidomide and bortezomib, could significantly improve the clinical outcome of PPCL, increasing response rate and duration, as well as survival. In this review we report an updated literature analysis about the current therapeutic scenario of PPCL, with a particular focus on the use of novel agents. [Copyright &y& Elsevier]

Abstract: This was a retrospective, comparative study focused on the extended follow-up of 192 transfusion-dependent patients with myelodysplastic syndromes treated (n. 83) or not treated (n. 109) with recombinant erythropoietin alpha (r-EPO) as single agent during the course of their disease. The results supported the safety of this treatment in the long term and also showed a significant survival advantage (median 52 months vs. 31 months, p <0.0095) in responding patients as compared to non-responding ones or to subjects never treated with r-EPO. At multivariate analysis, response to r-EPO maintained an independent prognostic value on OS. [Copyright &y& Elsevier]

Abstract: An epoxy formulation was modified by adding various amounts of an epoxy functionalized polyhedral oligomeric silsesquioxane (POSS). The obtained networks were characterized in terms of reactivity, viscoelastic behaviour and mechanical properties. Spectroscopy measurements by FT-NIR demonstrated that the epoxy groups of POSS were almost as reactive as those of the DGEBA in the curing stage, while in the post-curing a lower reactivity of the latter was found, possibly due to steric hindrance effects. The dynamic-mechanical analysis showed an increase in the storage modulus in both glassy and rubbery regions. On the other hand, T g and T β decreased with POSS content. The viscoelastic analysis showed that the addition of POSS enhanced the free volume and the tendency of the network to undergo thermal expansion. In particular, the β transition was made increasingly localized by increasing the POSS content. With respect to mechanical performances, the yield process was facilitated by incorporation of the POSS nanocages within the network, possibly due to an enhancement of the chain mobility. Fracture measurements showed an improvement of the parameters K c and G c up to 5wt% of POSS, after which a decrease of toughness was observed. These results were supported by a fractographic analysis. [Copyright &y& Elsevier]

Abstract: We investigated the effects of a single s.c. injection of peg-filgrastim in 32 patients with multiple myeloma who underwent autologous stem cell transplantation (AuSCT) as first line treatment. For comparison, 32 myeloma patients with similar characteristics and receiving standard daily administration of filgrastim were matched. Overall, there were no statistically significant differences between peg-filgrastim and filgrastim in terms of tolerability, marrow recovery, severity of neutropenia, incidence and duration of febrile neutropenia, documented infections and transfusions. However, some favourable trends or effects in favour of peg-filgrastim were observed. This was confirmed by a review of the published papers about this topic. [Copyright &y& Elsevier]

Abstract: The curing characteristics of a TGDDM/HHPA formulation have been investigated by Raman spectroscopy, which allowed us to monitor the evolution of the different reactive species (i.e. epoxy, anhydride and ester groups) participating in the curing process. The curing mechanism and, in particular, the role of side processes, were elucidated. NIR spectroscopy was employed to investigate the post-curing process, in view of the superior sensitivity of this technique for monitoring polar groups. Quantitative methods were developed to measure residual concentration of epoxy groups in the high conversion regimes (≥98%). Dynamic-mechanical measurements were performed to gather information on the molecular structure and viscoelastic properties of the investigated networks. For formulation rich in epoxy resin, clear evidence of an inhomogeneous phase structure was found. A viscoelastic analysis in terms of the WLF approach demonstrated that both the free volume and the thermal expansion coefficient of the networks decrease by enhancing the anhydride/epoxy molar ratio. [Copyright &y& Elsevier]

Abstract: FTIR spectroscopy has been used to investigate the microstructure of the inorganic phase in polyimide/silica hybrids obtained by the sol–gel route. It has been shown that the presence of a coupling agent (GOTMS) strongly influences the silica phase by favoring the formation of linear, branched chains which make the structure loosely interconnected. The morphological changes induced by GOTMS are reflected in the water sorption properties of the investigated systems. Due to the hydrophilic nature of the silica phase, the amount of sorbed water increases in the hybrid systems in comparison to the pristine polyimide, and among the two hybrids, increases more in the two-phase system than in the co-continuous. Molecular interactions of the hydrogen-bonding type have been identified between the imide units and the H2O molecules, both in the polyimide and in the hybrid systems. Finally, the sub-T g relaxation processes have been investigated in detail by dynamic-mechanical analysis coupled with molecular mechanics simulations. Considerable effects of the inorganic phase on these processes were observed, especially for the case of the co-continuous systems, and were accounted for by molecular scale contiguity among the phases. [Copyright &y& Elsevier]

Abstract: We investigated the therapeutic activity of recombinant erythropoietin (r-EPO) in association with thalidomide in 30 patients with myelodysplastic syndromes (MDS), previously treated with r-EPO (n.15, group A) or thalidomide (n.15, group B) as single agents, respectively, without any significant benefit on their anemia. Four patients of group A and three of group B (23.3%) achieved an erythroid response, according to International Working Group (IWG) criteria. After 12 weeks, responders of group A continued with thalidomide alone, those of group B with r-EPO alone. All responses were maintained, thus suggesting they were likely due to the second drug adjuncted (thalidomide for group A and r-EPO for group B), rather than to a combined effect. Our results do not support the hypothesis of a synergistic activity for the association of r-EPO and thalidomide on anemia of MDS. It seems, instead, that two populations of patients can be identified, according to their sensitivity to r-EPO or, alternatively, to thalidomide. [Copyright &y& Elsevier]

Abstract: By quantitative evaluation of the spectral changes associated with guest removal from clathrate films as well as by infrared dichroism measurements on uniaxially oriented films, three infrared absorbance peaks (at 1379, 1154 and 841cm−1) prevailingly associated with the amorphous phase have been located for syndiotactic polystyrene (s-PS) samples with helical crystalline phases. A detailed study relative to the infrared peaks in the wavenumber range 870–820cm−1, corresponding to phenyl C–H out-of-plane bending, has shown that the 841cm−1 peak is fully associated with conformationally disordered sequences only for samples including trans-planar crystalline phases (α and β) but not for samples including helical crystalline phases (γ, δ and clathrates). This result has been rationalized on the basis of different intermolecular interactions between phenyl rings, occurring for trans-planar and helical s-PS crystalline phases. Moreover, a preparation procedure leading to fully unoriented films has been described for helical semicrystalline films, which generally present different kinds of uniplanar orientation. FTIR spectra of these fully unoriented semicrystalline films, by subtracting out the amorphous phase contribution with a procedure based on the 1379cm−1 peak, have allowed a straightforward isolation of the spectra of the helical s-PS crystalline phases and the quantitative determination of the amorphous content. [Copyright &y& Elsevier]

Films of particulate polyimide–silica hybrids were produced by the sol–gel process from solution mixtures of a commercial polyamic acid and pre-hydrolysed tetraethoxysilane. Mechanical properties were evaluated at different temperatures, varying from 20 to 250 °C.The fracture toughness characteristics were studied by the ‘essential work of fracture’ method using double edge-notched specimens of different ligament lengths. The essential (we) and the non-essential or plastic work of fracture (βwp) were estimated from plots of the specific total work of fracture versus ligament length. The results showed that not only the modulus and yield strength but also the fracture toughness increased when submicron silica particles, produced by the sol–gel method, were dispersed in the polyimide matrix. In particular, it was found that both we and βwp increased with temperature to a larger extent than the parent polyimide. This enhancement in the fracture toughness was attributed primarily to extensive cavitations originating at the particle interface with the matrix. [Copyright &y& Elsevier]

Thalidomide exerts in vitro heterogeneous biological effects on hematopoiesis which have supported its possible use in treating myelodysplastic syndromes (MDS). Some recent clinical trials have confirmed that thalidomide may improve anemia and, less frequently, other cytopenias, in a proportion of younger patients with low-risk MDS (11–56%, on intention-to-treat analysis). Of interest, erythroid responses may be achieved also in transfusion-dependent subjects with high serum levels of endogenous erythropoietin, a subset of MDS patients with little chance of responding to recombinant erythropoietin, alone or in combination with G-CSF. Older patients, however, often do not tolerate the drug even at very low doses. How thalidomide acts in MDS is not clear. Some data suggest several mechanisms possibly involving stimulation of erythropoiesis through activation of physiological compensative mechanisms and reduction of apoptosis. The combination of thalidomide with other molecules active on hematopoiesis and the use of more effective and less toxic analogs are currently under clinical investigation. [Copyright &y& Elsevier]

Polyimide/silica hybrids were prepared by a sol–gel process and were evaluated in terms of curing behaviour, morphology and mechanical properties at different temperatures. The spectroscopic examinations showed that the presence of inorganic phase accelerates both the removal of the solvent and the concomitant imidization reaction. Two types of morphology for the silica phase were obtained by tailoring the composition of the precursor solution mixture. The mechanical properties were found to be strongly dependent on the system morphology. The largest increase in rigidity and strength properties were achieved when the two phases were co-continuous. Furthermore, these nanocomposites exhibited better mechanical properties also at high temperatures, thus extending the possible service temperature range of the polyimides. [Copyright &y& Elsevier]

• A SERS platform for Therapeutic Drug Monitoring of 6-Mercaptopurine. • Interaction mechanism and adsorbate structure. • Kinetics of the adsorption/aggregation processes. • Identification of a linearity range for reliable quantitative analysis. Gold colloidal solutions were investigated as SERS platforms for the detection and the quantitative analysis of the anticancer drug 6-Mercaptopurine. The study was aimed at verifying the feasibility of a SERS-based assaying method for Therapeutic Drug Monitoring. The interaction mechanism and the adsorbate structure were investigated by a QM vibrational analysis of the title molecule. Furthermore, a kinetic analysis of the adsorption/aggregation processes made by time- resolved SERS experiments and DLS analysis provided relevant information on the complex behaviour of the system. It was found that the adsorption process is fast and produces significant SERS signalling in the 5–20 μM range. At 15 and 20 μM composition, the kinetic analysis evidenced the formation of long-lived metastable aggregates; at 50 μM the colloidal solution collapsed immediately. A range of high linearity was identified between 5 and 20 μM, wherein a reliable quantitative analysis could be performed, with an estimated limiting sensitivity (LOD) of 1.0 μM. [ABSTRACT FROM AUTHOR]

• Micro patterning process to realize plasmonic sensors for SERS detection. • Spatially confined nanoparticle assemblies of gold colloid with suitable geometry and size. • Efficient SERS sensor with fairly homogeneous response and large Enhancement Factor. • Plasmonic sensor for hypersensitive analytical applications. Pyro-electrohydrodynamic jet printing (p-jet) has been used to fabricate a nanostructured plasmonic sensor for SERS spectroscopy. The p-jet approach allowed us to have an assembly of nanoparticles with suitable geometry and size, which resulted in a sensing surface with intense SERS activity and a rather homogeneous response. Raman imaging measurements highlighted strong Enhancement Factors across the sensing area, exceeding those of the pristine colloidal solution by almost two orders of magnitude. The intense plasmonic effect was further demonstrated by the spectroscopic recognition of a metal-catalyzed dimerization process triggered to completeness at the metal surface. The results presented herein demonstrate the usefulness of the proposed SERS sensor for hypersensitive molecular analysis. [ABSTRACT FROM AUTHOR]

Abstract: Twenty-one patients with multiple myeloma, all relapsed after frontline autologous stem cell transplantation and all relapsed again after or resistant to thalidomide (employed as second line treatment) received bortezomib (1.3mg/m2 body surface twice weekly for 2 weeks followed by an interval of 10–12 days) without adjunct of steroids as third line therapy. Three patients died of progressive disease during the first 2 cycles with bortezomib. Eighteen patients received at least 2 cycles and were evaluated for response. According to EBMT criteria, two complete (negative immunofixation) and seven partial (reduction of M-component > 50–75%) remissions were achieved (ITT response rate 42.8%). Duration of response lasted from 2 to 14+ months. Grades 3–4 toxicities (thrombocytopenia, leucopenia, peripheral neuropathy and vasculitis) were observed in seven patients, but no patient interrupted the treatment due to side effects. We conclude that bortezomib alone may induce high quality responses as third line salvage therapy with acceptable toxicity in a significant proportion of homogeneously pre-treated myeloma patients with progressive disease after autologous transplantation and thalidomide. [Copyright &y& Elsevier]