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The present research focuses on a continuum description of stratified metamaterials achieved through the superposition of layers with alternating chirality. Each layer is constructed as a periodic assembly of centre-symmetric periodic cells, formed by a recurring arrangement of rigid circular discs connected by elastic ligaments. The layers are interconnected through elastic pins passing through the centres of aligned discs, allowing for either restrained or free relative rotation. A micropolar continuum model is used to describe each individual layer. The overall response of the metamaterials to in-plane forces is derived using a multi-field non-local model, expressed in terms of the average and difference of displacement and rotational fields. The overall micropolar and standard (Cauchy) constitutive tensors have been determined in closed form. The validity of the equivalent generalized micropolar model has been confirmed through comparison with discrete Lagrangian solutions of representative examples. In addition, a detailed analysis of a pseudo-indentation test has been carried out. This article is part of the theme issue 'Current developments in elastic and acoustic metamaterials science (Part 2)'. [ABSTRACT FROM AUTHOR]

This article focuses on characterizing a class of quasi-periodic metamaterials created through the repeated arrangement of an elementary cell in a fixed direction. The elementary cell consists of two building blocks made of elastic materials and arranged according to the generalized Fibonacci sequence, giving rise to a quasi-periodic finite microstructure, also called Fibonacci generation. By exploiting the transfer matrix method, the frequency band structure of selected periodic approximants associated with the Fibonacci superlattice, i.e. the layered quasi-periodic metamaterial, is determined. The self-similarity of the frequency band structure is analysed by means of the invariants of the symplectic transfer matrix as well as the transmission coefficients of the finite clusters of Fibonacci generations. A high-frequency continualization scheme is then proposed to identify integral-type or gradient-type non-local continua. The frequency band structures obtained from the continualization scheme are compared with those derived from the Floquet–Bloch theory to validate the proposed scheme. This article is part of the theme issue 'Current developments in elastic and acoustic metamaterials science (Part 1).' [ABSTRACT FROM AUTHOR]

The present research focuses on a continuum description of stratified metamaterials achieved through the superposition of layers with alternating chirality. Each layer is constructed as a periodic assembly of centre-symmetric periodic cells, formed by a recurring arrangement of rigid circular discs connected by elastic ligaments. The layers are interconnected through elastic pins passing through the centres of aligned discs, allowing for either restrained or free relative rotation. A micropolar continuum model is used to describe each individual layer. The overall response of the metamaterials to in-plane forces is derived using a multi-field non-local model, expressed in terms of the average and difference of displacement and rotational fields. The overall micropolar and standard (Cauchy) constitutive tensors have been determined in closed form. The validity of the equivalent generalized micropolar model has been confirmed through comparison with discrete Lagrangian solutions of representative examples. In addition, a detailed analysis of a pseudo-indentation test has been carried out. This article is part of the theme issue 'Current developments in elastic and acoustic metamaterials science (Part 2)'. [ABSTRACT FROM AUTHOR]

Background: Pure red cell aplasia (PRCA) is a possible complication after allogeneic hematopoietic stem cell transplantation (HSCT) with major ABO incompatibility. Patients experience delayed engraftment of the erythroid series, with prolonged transfusion-dependent anemia and iron overload. Methods: We performed a revision of the most recent literature about post-HSCT PRCA treatment procedures. Moreover, we conducted a retrospective study, over the last 13-years, which included all consecutive major ABO mismatched HSCT performed in our unit, with the aim to assess PRCA incidence, risk factors, and response to different treatments. Overall, 194 patients received a major ABO mismatched transplant from 2010 to 2022. For each patient, data about demographic and transplant characteristics, engraftment, blood transfusion, and possible treatment received were collected. Results: The literature review returned 23 eligible papers on PRCA treatment, with high success rate using plasma-exchange (PEX) and immunoadsorption procedures, daratumumab, and eltrombopag. Our study identified a total of 24 cases of PRCA. Among risk factors for PRCA development, we have found older recipient age (p=0.01), high pre-HSCT IgG and IgM IHA titer (p<0.0001), major rather than bidirectional ABO incompatibility (p=0.02), low T CD8 lymphocyte count in the graft (p=0.006), relative donor (p=0.02) and bone marrow as stem cell source (p=0.002). However, multivariate analysis confirmed only pre-HSCT IgG IHA titer as the unique risk factor for PRCA occurrence. The optimal cut-off value of pre-HSCT IgG IHA for PRCA development, resulted to be 1/64, with a 100% sensitivity and 68.8% specificity (p<0.0001). All patients with PRCA had received rhEPO and transfusion support and 20 patients received additional treatments like PEX, rituximab, and more recently daratumumab. Comprehensively, PEX and rituximab obtained a response in half of the cases, at a variable time, while the few cases of patients we treated with daratumumab suggest promising results. The overall response rate in our cohort was 75%, with significantly better survival (94.4% vs. 16.7%) and lower transplant-related mortality (6.3% vs. 80%) for PRCA responders. Conclusions: Standardized guidelines on when and how to treat PRCA are necessary because the current treatment is controversial among centers. [ABSTRACT FROM AUTHOR]

This paper deals with the free propagation problem of resonant and close-to-resonance waves in one-dimensional lattice metamaterials endowed with nonlinearly viscoelastic resonators. The resonators' constitutive and geometric nonlinearities imply a cubic coupling with the lattice. The analytical treatment of the nonlinear wave propagation equations is carried out via a perturbation approach. In particular, after a suitable reformulation of the problem in the Hamiltonian setting, the approach relies on the well-known resonant normal form techniques from Hamiltonian perturbation theory. It is shown how the constructive features of the Lie Series formalism can be exploited in the explicit computation of the approximations of the invariant manifolds. A discussion of the metamaterial dynamic stability, either in the general or in the weak dissipation case, is presented. [ABSTRACT FROM AUTHOR]

Hemorrhagic cystitis (HC) is a highly impacting complication in allogeneic hematopoietic stem cell transplantation (HSCT), occurring in 12%–37% of patients. The impact of transplant‐ and patient‐specific variables has been described, with a possible role for JCV and BKV, which may be cooperating with cytomegalovirus (CMV). Here, we analyze 134 letermovir‐exposed, CMV‐free patients, treated with the same cyclophosphamide‐based graft‐versus‐host disease (GVHD) prophylaxis, describing risk factors for HC. The overall incidence of HC was 23%. Patients with HLA mismatched transplant, higher comorbidity score, and receiving three alkylating agents with TBF (thiotepa, busulfan, and fludarabine) conditioning regimen had a higher risk of HC in multivariate analysis (OR: 4.48, 6.32, and 1.32, respectively). A HC‐score including male gender, TBF conditioning, and HLA‐mismatch stratifies the risk of HC in the first 100 days after HSCT. The role of BKV and JCV was not highly impacting in those patients, suggesting a possible synergistic effect between CMV and JCV in causing HC. HC can be interpreted as the combination of patient‐related factors, chemotherapy‐related toxicities—especially due to alkylating agents—and immunological elements. [ABSTRACT FROM AUTHOR]

Block-lattice materials featuring periodic planar running-bond tessellation of regular rigid blocks and linear elastic homogeneous isotropic interfaces are considered. The governing equations of the discrete masonry-like Lagrangian model are properly manipulated via the novel enhanced continualization scheme, in such a way as to obtain equivalent integral type non-local continua, whose band structure turns out to be coincident with that of the corresponding discrete models. The formal Taylor series expansion of the integral kernels allows deriving homogeneous generalized micropolar higher-order continuum models, characterized by non-local constitutive and inertial terms. The enhanced continualization exhibits thermodynamic consistency in the definition of the overall non-local constitutive tensors, as well as qualitative agreement and quantitative convergent matching of the complex frequency band structure in the regime of both homogeneous and non-homogeneous Bloch waves. The theoretical findings are effectively validated by studying the dispersion relations and the spatial attenuation properties, as referred to realistic representative cases of masonry-like block-lattice micro-structures. [ABSTRACT FROM AUTHOR]

Depressive disorders are the most common manifestation of psychological distress in allogenic hematopoietic stem cell transplantation. Few studies have yet investigated the relationship between therapeutic educational interventions and outcomes in these patients with specific attention to those related to mental health. Aim of this study was to understand how much educational intervention can represent a protective factor in preventing psycho-emotional distress-related issues in this setting. A prospective observational study of a multicenter cohort was conducted. Adult patients undergoing allogeneic hematopoietic stem cell transplantation. A pre-transplant therapeutic educational programme was offered to a cohort of adult patients undergoing allo-HSCT recruited in ten transplant centers of the GITMO network between May 2018 and January 2019. Depression, Anxiety and Stress scale was used to collect data on psycho-emotional distress at admission (T0), at the day of transplant (T1) and at discharge (T2). Descriptive data were collected and reported, and comparative analyses were done among patients who were compliant with the pre-transplant educational intervention and those who did not (for any reason). A cohort of 133 allo-HSCT patients was observed. In patients who did not receive pre-transplant educational intervention, higher levels of depression at admission (p = 0.01) and at the day of transplant (p = 0.03), higher levels of anxiety (p = 0.01 and p = 0.01 respectively) as well as higher levels of stress (p < 0.01 and p = 0.01) were observed. Problem solving and "face to face" interview were the best methods to provide education to patients. Those who received pre-transplant education through "face-to-face" interview reported significant low levels of depression during the whole hospital stay period (p < 0.01; p = 0.01; p = 0.01) and less anxiety and stress at admission (p < 0.05 and p = 0.01 respectively). Depression was more represented in female than male participants at T0 (16.5% vs 9.0%; p = 0.01), while among T0 and T2 the males had a significant higher increasing of depression than females (p = 0.03). Our study demonstrated that pretreatment therapeutic educational programs with specific learning modalities can be effective in limiting the potential risk of developing moderate-to-severe anxiety-depressive states and stress symptoms related to allo-HSCT. Further studies are needed to confirm our results and to understand whether containing psycho-emotional distress can have any relationship with medium- and long-term post-transplant complications. [ABSTRACT FROM AUTHOR]

Summary: Cytokine release syndrome (CRS) and consumptive coagulopathy can complicate the treatment with chimeric antigen receptor T (CAR‐T) cells. The modified version of the Endothelial Activation and Stress Index (mEASIX), a score derived from haematopoietic stem cell transplantation, combines platelets, C‐reactive protein (CRP), and lactate dehydrogenase (LDH) and has been correlated with CRS and endothelial biomarkers. In 38 consecutive patients with aggressive lymphoproliferative disease we measured a coagulative laboratory panel at baseline and early after infusion of anti‐CD19 CAR‐T. The panel was investigated also in the presence of CRS graded 2 or higher, or immune effector cell‐associated neurotoxicity syndrome (ICANS). Moreover, we examined the relationship between mEASIX, coagulation biomarkers, and toxicities of CAR‐T cells. During CRS grade 2 or higher, we found increased prothrombin time (PT) and activated partial thromboplastin time (aPTT), fibrinogen, D‐dimer, factor VIII (FVIII), and von Willebrand factor (vWF) antigen levels, and decreased platelet count and antithrombin levels. The occurrence of immune effector cell‐associated neurotoxicity syndrome was associated with higher PT values, D‐dimer, FVIII, and vWF levels, and decreased fibrinogen levels and platelet count. A higher mEASIX score correlated with increased aPTT values, fibrinogen, D‐dimer, FVIII and vWF levels, and decreased antithrombin levels. Baseline mEASIX was predictive for consumptive coagulopathy and CRS graded 2 or higher, and for progression‐free survival and overall survival. [ABSTRACT FROM AUTHOR]

Background: In the last decade, many steps forward have been made in acute myeloid leukemia prognostic stratification, adding next-generation sequencing techniques to the conventional molecular assays. This resulted in the revision of the current risk classification and the introduction of new target therapies. Aims and methods: We wanted to evaluate the prognostic impact of acute myeloid leukemia (AML) mutational pattern on relapse occurrence and survival after allogeneic stem cell transplantation. A specific next-generation sequencing (NGS) panel containing 26 genes was designed for the study. Ninety-six patients studied with NGS at diagnosis were included and retrospectively studied for post-transplant outcomes. Results: Only eight patients did not show any mutations. Multivariate Cox regression revealed FLT3 (HR, 3.36; p=0.02), NRAS (HR, 4.78; p=0.01), TP53 (HR, 4.34; p=0.03), and WT1 (HR 5.97; p=0.005) mutations as predictive variables for relapse occurrence after transplantation. Other independent variables for relapse recurrence were donor age (HR, 0.97; p=0.04), the presence of an adverse cytogenetic risk at diagnosis (HR, 3.03; p=0.04), and the obtainment of complete remission of the disease before transplantation (HR, 0.23; p=0.001). Overall survival appeared to be affected only by grade 2--4 acute GvHD occurrence (HR, 2.29; p=0.05) and relapse occurrence (HR, 4.33; p=0.0001) in multivariate analysis. Conclusions: The small number of patients and the retrospective design of the study might affect the resonance of our data. Although results on TP53, FLT3, and WT1 were comparable to previous reports, the interesting data on NRAS deserve attention. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the role of WT1 expression after allogeneic stem cell transplantation (alloHSCT) in patients with acute myeloid leukemia (AML). We studied WT1 expression in bone marrow cells from 50 patients in complete remission on day +60 after transplant. WT1 was assessed on unfractionated bone marrow mononuclear cells (MNC) and on CD34+ selected cells (CD34+). A ROC curve analysis identified 800 WT1 copies on CD34+ selected cells, as the best cut-off predicting relapse (AUC 0.842, p=0.0006, 85.7% sensitivity and 81.6% specificity) and 100 copies in MNC (AUC 0.819, p=0.007, 83.3% sensitivity and 88.2% specificity). Using the 800 WT1 copy cut off in CD34+ cells, the 2 year cumulative incidence of relapse was 12% vs 38% (p=0.005), and 2 year survival 88% vs 55% (p=0.02). Using the 100 WT1 copy cut off in unfractionated MNC, the 2 year cumulative incidence of relapse 13% vs 44% (p=0.01) and the 2 year survival 88% vs 55% (p=0.08). In a multivariate Cox analysis WT1 expression in CD34 cells proved to highly predictive of relapse (p=0.004); also WT1 expression on unfractionated cells predicted relapse (p=0.03). In conclusion, day-60 WT1 expression after allogeneic HSCT is a significant predictor of relapse, particularly when tested on CD34+ selected bone marrow cells. [ABSTRACT FROM AUTHOR]

Although the effects of malnutrition on morbidity and mortality in adult patients undergoing allogeneic hematopoietic stem cell transplantation are clear, the relationship with quality of life (QOL) is less clear. The purpose of this study was to assess the relationship between malnutrition and QOL. A prospective observational study was conducted in 36 adult patients undergoing allogeneic hematopoietic stem cell transplantation. Adapted criteria of the Global Leadership Initiative on malnutrition have been used for the diagnosis of malnutrition in clinical settings. A cancer linear analog scale was used to assess QOL. Overall QOL at 14 days after allogeneic hematopoietic stem cell transplantation was 37.1 (95% CI 2.9–45.39) in patients without severe malnutrition, versus 16.0 (95% CI − 6.6 to 38.6) in patients with severe malnutrition (p = 0.05). At discharge, it was 48.0 (95% CI 38.4–57.6) versus 34.0 (95% CI 4.1–63.9) (p = 0.27). The results of our study suggest that patients with severe malnutrition at discharge tend to have worse QOL. A larger cohort of patients is required to confirm this hypothesis. [ABSTRACT FROM AUTHOR]

This letter, published in the Annals of Hematology, describes a case of acute erythroid leukemia (AEL) in a 70-year-old female patient. The patient presented with lumbar pain and was found to have leukocytosis, thrombocytopenia, and anemia. Further examination revealed a complex karyotype, a TP53 mutation, and the presence of the BCR/ABL1 fusion gene. The authors discuss the challenges in classifying and managing this type of leukemia, emphasizing the need for further research and novel therapeutic approaches. [Extracted from the article]

Purpose: Hemorrhagic cystitis (HC) is a frequent complication of allogeneic hematopoietic stem-cell transplantation (HSCT). HC worsens transplant outcomes and patient wellbeing in terms of pain, hospitalization, and need for supportive care. A deeper understanding of the risk factors of HC may lead to more intensive prevention in high-risk patients.Methods: In this report, we analyzed 237 consecutive patients who received HSCT with the aim of identifying possible risk factors for HC and their consequences, with a particular focus on transplant- and gender-related risk factors.Results: HC occurred in 17% of patients, with a higher incidence in males (21% vs 11%, p = 0.03). Risk factors identified for HC included age over 55 years, male recipient, HLA mismatch, reduced intensity conditioning, and cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis. Increased HC was seen in patients with grade II-IV acute GVHD and detectable BKV and JCV viruria. In a multivariate model, increased age remained significant (p = 0.013). Patients with HC had longer hospitalizations and increased non-relapse mortality (NRM). Among male recipients, independent risk factors for HC included age (p = 0.016) and prostate volume (p = 0.016). Prostatic hyperplasia (volume more than 40 cm3) occurred in 33% of male patients, of which 32% developed HC (compared with 16% of patients without prostatic hyperplasia; p = 0.032).Conclusions: Age is the most important risk factor for HC. Additional potential risk factors include cyclophosphamide-based GVHD prophylaxis and HLA mismatch. Among male recipients, prostatic hyperplasia is an additional independent risk factor. As HC is common and associated with prolonged hospitalization, more intensive prophylactic strategies should be considered in high-risk patients. [ABSTRACT FROM AUTHOR]

The cellular microstructure of periodic architected materials can be enriched by local intracellular mechanisms providing innovative distributed functionalities. Specifically, high-performing mechanical metamaterials can be realized by coupling the low-dissipative cellular microstructure with a periodic distribution of tunable damped oscillators, or resonators, vibrating at relatively high amplitudes. The benefit is the actual possibility of combining the design of wave-stopping bands with enhanced energy dissipation properties. This paper investigates the nonlinear dispersion properties of an archetypal mechanical metamaterial, represented by a one-dimensional lattice model characterized by a diatomic periodic cell. The intracellular interatomic interactions feature geometric and constitutive nonlinearities, which determine cubic coupling between the lattice and the resonators. The non-dissipative part of the coupling can be designed to exhibit a softening or a hardening behavior, by independently tuning the geometric and elastic stiffnesses. The nonlinear wavefrequencies and waveforms away from internal resonances are analytically determined by adopting a perturbation technique. The employed approach makes use of tools borrowed from Hamiltonian perturbation theory, together with techniques often used in the context of nearly-integrable Hamiltonian systems.The dispersion spectra are determined in closed, asymptotically approximate, form as a nonlinear function of the time-dependent decreasing amplitude decrement. The invariant manifolds defined by the harmonic periodic motions are also analytically determined. The asymptotic results are further validated numerically. [ABSTRACT FROM AUTHOR]

Autologous stem cell transplantation (ASCT) is a good option in fit young patients affected by POEMS syndrome. Few data are published on how to treat these patients in case of relapse. In this paper we described our two patients who underwent a second ASCT. From our experience, we can confirm that a second transplant is a real treatment option with good results and limited side effects. It provided excellent response and long-term disease-free survival in POEMS patients who relapsed after a first transplant, including late relapses. [ABSTRACT FROM AUTHOR]

In the present study, matrix perturbation bounds on the eigenvalues and on the invariant subspaces found by principal component analysis is investigated, for the case in which the data matrix on which principal component analysis is performed is a convex combination of two data matrices. The application of the theoretical analysis to multi-objective optimization problems – e.g., those arising in the design of mechanical metamaterial filters – is also discussed, together with possible extensions. [ABSTRACT FROM AUTHOR]

This retrospective study assessed the effectiveness of eltrombopag (EPAG), a thrombopoietin receptor agonist, in the treatment of poor graft function (PGF) following an allogeneic haemopoietic stem cell transplantation (HSCT). Complete response was defined as normalization of blood counts, whereas partial response was defined as transfusion independence. A total of 48 patients with full donor chimerism after HSCT, received EPAG for a median of 120 days (range 10–591). Patients with uni- bi- or tri-lineage cytopenia started treatment at a median of 95 days (range 17–877) after HSCT. The overall response rate was 75%: 24 patients had a complete response and 12 had a partial response. Positive predictors of response were an HLA-matched donor, a CD34+ dose at transplant > 4 × 106/kg, and starting EPAG treatment at least 90 days after HSCT. Patients with more than one positive predictor had a response rate of 92% for the overall patient cohort and 94% for patients with tri-lineage cytopenia. One-year survival was 89% for complete responders, 60% for partial responders and 20% for non-responders (p = 0.0004). EPAG improves peripheral blood counts in patients with poor graft function following HSCT. Response to EPAG can be predicted and has a significant impact on survival. [ABSTRACT FROM AUTHOR]

The aim of this review is to update the current status of allogeneic hemopoietic stem cell transplants (HSCT) for patients with myelofibrosis (MF). We have first summarized the issue of an indication for allogeneic HSCT, discussing several prognostic scoring systems, developed to predict the outcome of MF, and therefore to identify patients who will benefit of an allogeneic HSCT. Patients with low risk MF are usually not selected for a transplant, whereas patients with intermediate or high risk MF are eligible. A separate issue, is how to predict the outcome of HSCT: we will outline a clinical molecular myelofibrosis transplant scoring system (MTSS), which predicts overall survival, ranging from 90% for low risk patients, to 20% for very high risk patients. We will also discuss transfusion burden and spleen size, as predictors of transplant outcome. The choice of a transplant platform including the conditioning regimen, the stem cell source and GvHD prophylaxis, are crucial for a successful program in MF, and will be outlined. Complications such as poor graft function, graft failure, GvHD and relapse of the disease, will also be reviewed. Finally we discuss monitoring the disease after HSCT with donor chimerism, driver mutations and hematologic data. We have made an effort to make this review as comprehensive and up to date as possible, and we hope it will provide some useful data for the clinicians. [ABSTRACT FROM AUTHOR]

Classification of myeloproliferative neoplasms is based on hematologic, histopathologic, and molecular characteristics, including the BCR-ABL1 and JAK2 V617F or MPL and CALR. Although the different gene mutations ought to be mutually exclusive, several cases with cooccurring BCR-ABL1 and JAK2 V617F or CALR have been identified with a frequency of 0.2-2.5% in the European population. The tyrosine kinase abnormalities appeared to affect independent subclones because imatinib mesylate (IM) treatment induced Ph+-CML remission, whereas the JAK2V617F clone either persisted or clinically expanded after a major response of Ph+-clone. Allogeneic stem cell transplantation is at present the only potentially curative therapy for these patients after therapy with ruxolitinib and TKI inhibitor. We describe the case of 3 young people treated in our institution for the coexistence of BCR/ABL chronic myeloid leukemia and another Philadelphia chromosome-negative (Ph-) Chronic myeloproliferative disease. They received ruxolitinib, imatinib/nilotinib, and allogeneic transplantation with safe and efficient results. [ABSTRACT FROM AUTHOR]

Recently, an increasing research effort has been dedicated to analyze the transmission and dispersion properties of periodic acoustic metamaterials, characterized by the presence of local resonators. Within this context, particular attention has been paid to the optimization of the amplitudes and center frequencies of selected stop and pass bands inside the Floquet–Bloch spectra of the acoustic metamaterials featured by a chiral or antichiral microstructure. Novel functional applications of such research are expected in the optimal parametric design of smart tunable mechanical filters and directional waveguides. The present paper deals with the maximization of the amplitude of low-frequency band gaps, by proposing suitable numerical techniques to solve the associated optimization problems. Specifically, the feasibility and effectiveness of Radial Basis Function networks and Quasi-Monte Carlo methods for the interpolation of the objective functions of such optimization problems are discussed, and their numerical application to a specific acoustic metamaterial with tetrachiral microstructure is presented. The discussion is motivated theoretically by the high computational effort often needed for an exact evaluation of the objective functions arising in band gap optimization problems, when iterative algorithms are used for their approximate solution. By replacing such functions with suitable surrogate objective functions constructed applying machine-learning techniques, well-performing suboptimal solutions can be obtained with a smaller computational effort. Numerical results demonstrate the effective potential of the proposed approach. Current directions of research involving the use of additional machine-learning techniques are also presented. [ABSTRACT FROM AUTHOR]

Acoustic metamaterials are artificial microstructured media, typically characterized by a periodic locally resonant cell. The cellular microstructure can be functionally customized to govern the propagation of elastic waves. A one-dimensional diatomic lattice with cubic inter-atomic coupling—described by a Lagrangian model—is assumed as minimal mechanical system simulating the essential undamped dynamics of nonlinear acoustic metamaterials. The linear dispersion properties are analytically determined by solving the linearized eigenproblem governing the free wave propagation in the small-amplitude oscillation range. The dispersion spectrum is composed by a low-frequency acoustic branch and a high-frequency optical branch. The two frequency branches are systematically separated by a stop band, whose amplitude is analytically derived. Superharmonic 3:1 internal resonances can occur within a wavenumber-dependent locus defined in the mechanical parameter space. A general asymptotic approach, based on the multiple scale method, is employed to determine the nonlinear dispersion properties. Accordingly, the nonlinear frequencies and waveforms are obtained for the two fundamental cases of non-resonant and superharmonically 3:1 resonant or nearly resonant lattices. Moreover, the invariant manifolds associated with the nonlinear waveforms are parametrically determined in the space of the two principal coordinates. Finally, some examples of non-resonant and resonant lattices are selected to discuss their nonlinear dispersion properties from a qualitative and quantitative viewpoint. [ABSTRACT FROM AUTHOR]

The acoustic dispersion properties of monodimensional waveguide filters can be assessed by means of the simple prototypical mechanical system made of an infinite stack of periodic massive blocks, connected to each other by elastic joints. The linear undamped dynamics of the periodic cell is governed by a two degree-of-freedom Lagrangian model. The eigenproblem governing the free propagation of shear and moment waves is solved analytically and the two dispersion relations are obtained in a suited closed form fashion. Therefore, the pass and stop bandwidths are conveniently determined in the minimal space of the independent mechanical parameters. Stop bands in the ultra-low frequency range are achieved by coupling the stacked material with an elastic half-space modelled as a Winkler support. A convenient fine approximation of the dispersion relations is pursued by formulating homogenised micropolar continuum models. An enhanced continualization approach, employing a proper Maclaurin approximation of pseudo-differential operators, is adopted to successfully approximate the acoustic and optical branches of the dispersion spectrum of the Lagrangian models, both in the absence and in the presence of the elastic support. [ABSTRACT FROM AUTHOR]

To avoid risk for allogeneic transfusions in healthy bone marrow (BM) donors, 1–2 preoperative autologous blood donations (PAD) are usually collected before the BM harvest. We analysed the haematological parameters in BM donors before and after the harvest, to assess the efficacy of this practice in limiting the postharvest anaemia. Overall, 102 consecutive donors underwent BM harvest preceded by one (26 cases) or two PAD (76 cases), which were infused during BM collection. We analysed the parameters related to donors, PAD timing and BM graft characteristics. PAD induced a significant decrease in Hb (from 14·6 g/dl, IQ range 13·3–15·5 to12·9 g/dl, IQ range 11·8–13·9; P < 0·0001) in all donors, with a median Hb loss at day −1 of 10·9% (IQ range 6·8–14·2). The PAD‐related Hb decrease was independent of sex or number of PAD, and was inversely related to the time elapsed from first or last PAD. In comparison with values recorded at day‐1, BM harvest produced an additional Hb decrease, accounting for a median Hb loss of 18·9% (IQ range 14·9–24·4). Overall, in comparison with pre‐PAD values, Hb levels at day +1 were reduced of 28·9% (IQ range 23·6–32·2), independently if donors had 1 or 2 PAD reinfused. In conclusion, these data show that two PAD do not carry any advantage over one PAD. An eventual benefit of PAD can be achieved only if an adequate interval between PAD and BM harvest elapses. Prospective randomized studies could be worth to establish if any role for PAD does exist in BM donors. [ABSTRACT FROM AUTHOR]

Ibrutinib efficacy and tolerability in patients with relapsed chronic lymphocytic leukemia following allogeneic HCT. Keywords: allogeneic transplant; CLL; ibrutinib EN allogeneic transplant CLL ibrutinib 267 269 3 04/15/21 20210401 NES 210401 CONFLICT OF INTEREST All the authors declare no conflict of interest. Patients who relapsed more than 24 months from allo-HSCT had a 2 years PFS probability of 73,3%, compared to 44,3% of CLL patients who relapsed within 24 months from transplant.11 All together these published data confirm the utility of IBR as salvage therapy in relapse CLL patients after allo-HSCT, and seems that IBR was particularly effective if the relapse occurred after 24 months. [Extracted from the article]

Gastrointestinal graft-versus-host disease (GvHD) represents a life-threatening complication after stem cell transplantation. Differential diagnosis between gut GvHD and other causes of diarrhea after HSCT is still subjected to endoscopy and histological findings. The research for a reliable biomarker for gut GvHD might allow an early diagnosis of this condition and a consequent prompt treatment that could reduce unfavorable outcomes. Recently, fecal calprotectin was reported as reliable marker of gut involvement. We would evaluate if serum instead of fecal calprotectin could be considered a possible biomarker of gut GvHD. Serum calprotectin was measured in a cohort of 54 patients submitted to allogeneic stem cell transplantation using ELISA assay. For a subset of 21 patients, calprotectin serum levels were compared with fecal calprotectin detection. Contrary to fecal calprotectin, we found only a trend to high level of serum calprotectin for GvHD development and gut involvement, but statistical difference was not reached. Fecal but not serum calprotectin could be considered as possible biomarker for gut GvHD. [ABSTRACT FROM AUTHOR]

This work deals with the micromechanical study of periodic thermo-diffusive elastic multi-layered materials, which are of interest for the fabrication of solid oxide fuel cells. The focus is on the dynamic regime that is investigating the dispersive wave propagation within the periodic material. In this framework, a generalization of the Floquet–Bloch theory is adopted, able to determine the complex band structure of such materials. The infinite algebraic linear system, obtained by exploiting both bilateral Laplace transform and Fourier transform, is replaced by its finite counterpart, resulting from a proper truncation at a finite number of considered unknowns and equations. A regularization technique is herein useful to get rid of the Gibbs phenomenon. The solution of the problem is, finally, found in terms of complex angular frequencies, corresponding to a finite sequence of eigenvalue problems for given values of the wave vector. The paper is complemented by numerical examples taking into account thermo-mechanical coupling. The frequency band structure of the periodic thermo-diffusive elastic material is found to be strongly influenced by the interaction between thermal and mechanical phenomena. [ABSTRACT FROM AUTHOR]

Background: We evaluated the impact of center expertise, in terms of number of patients treated, on the overall survival (OS) and progression‐free survival (PFS) of patients with head and neck squamous cell carcinoma (SCC). Methods: We performed a pooled analysis including data from 6 randomized trials in head and neck SCC conducted in Italy. We evaluated the association between OS or PFS and the number of patients recruited by the center. Results: The outcome of 903 patients who had received radiotherapy (RT) was analyzed (median follow‐up 76 months). The hazard ratio (HR) comparing the third and the first quartiles of the distribution of number of patients per center showed an advantage in PFS (HR 0.59, range 0.53‐0.65, P < .0001) and in OS (HR 0.70, 0.60‐0.81, P < .0001) for centers with a higher number of patients recruited. A similar benefit was observed in PFS (HR 0.63, 0.60‐0.66) and OS (HR 0.74, 0.69‐0.79) considering the mean number of patients per year. Conclusions: The PFS and OS were longer for patients treated in high‐case‐volume centers. [ABSTRACT FROM AUTHOR]

Five patients showed a normal karyotype, 1 patient had hypodiploidy, and 3 patients had a complex karyotype. At the end of the induction treatment, 5 (55%) patients showed a CR, 3 patients showed a PR, and 1 was unresponsive. Only 3 patients (33%) showed side effects during the induction phase: in 2 patients, infection and neutropenia during induction therapy regressed through appropriate treatment, while another presented a transitory peripheral neuropathy. [Extracted from the article]

POEMS syndrome is a rare paraneoplastic condition, with a poorly understood pathogenesis. High dose chemotherapy followed by autologous stem cell transplantation (ASCT) has been reported to be an effective therapeutic option for patients with good performance status. Here, we review the role of ASCT for POEMS syndrome and discuss indications together with advantages and disadvantages, and related issues such lenalidomide given before or after ASCT, VEGF levels as a marker of disease, and different regimens for stem cell mobilization. [ABSTRACT FROM AUTHOR]

Background: Incidence of graft-versus-host disease (GVHD) in haploidentical bone marrow (BM) transplants using posttransplantion cyclophosphamide (PT-Cy) is low, whereas GVHD using mobilized peripheral blood stem cells (PBSC) ranges between 30% and 40%.Methods: To evaluate the effect of stem cell source in haploidentical transplantation with PT-Cy, we analyzed 451 patients transplanted for acute myeloid leukemia or acute lymphoblastic leukemia reported to the European Society for Blood and Marrow Transplantation.Results: BM was used in 260 patients, and PBSC were used in 191 patients. The median follow-up was 21 months. Engraftment was lower in BM (92% vs 95%, P < 0.001). BM was associated with a lower incidence of stage II-IV and stage III-IV acute GVHD (21% vs 38%, P ≤ .01; and 4% vs 14%, P < .01, respectively). No difference in chronic GVHD, relapse, or nonrelapse mortality were found for PBSC or BM. The 2-year overall survival (OS) was 55% versus 56% (P = .57) and leukemia-free survival (LFS) was 49% versus 54% (P = .74) for BM and PBSC, respectively. On multivariate analysis, PBSC were associated with an increased risk of stage II-IV (hazard ratio [HR], 2.1; P < .001) and stage III-IV acute GVHD (HR, 3.8; P < .001). For LFS and OS, reduced intensity conditioning was the only factor associated with treatment failure (LFS: HR, 1.40; P = .04) and relapse (HR, 1.62; P = .02).Conclusion: In patients with acute leukemia in first or second remission receiving haploidentical transplantation with PT-Cy, the use of PBSC increases the risk of acute GVHD, whereas survival outcomes are comparable. Cancer 2018;124:1428-37. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Lattice materials are often investigated to determine how small parameter variations in the periodic microstructrure can influence the elastic wave propagation. A general hierarchical scheme, based on asymptotic perturbation techniques, is outlined to analytically assess the parametric sensitivity of the material band structure to a generic multi-parametric perturbation (direct problem). Modeling refinements, parameters updates, microstructural damages and manufacturing irregularities can be treated indifferently and simultaneously. According to a converse strategy, based on the inversion of the sensitivity problem, a hierarchical scheme is sketched to identify the parameter combinations which realize a design band structure (inverse problem). The direct and inverse problem are applied to the sensitivity analysis and band structure design of the anti-tetrachiral lattice material. Despite the high spectral density and the high-dimensional parameter space, the multi-parameter perturbation technique demonstrates its suitability in, first, analytically—although asymptotically—describe the material spectrum and, second, designing the material microstructure to obtain the desired spectral components. The inverse problem solution is discussed in terms of existence, uniqueness, asymptotic consistency and physical admissibility. [ABSTRACT FROM AUTHOR]

Background: Therapy related myeloid neoplasms (t-MN) occur due to direct mutational events of chemotherapeutic agents and radiotherapy. Disease latency, mutational events and prognosis vary with drugs categories. Methods: We describe a cohort of 30 patients, 18 females and 12 males, with median age of 52.5 years (range, 20 to 64), submitted to allogeneic stem cell transplantation (HSCT) in our department between September 1999 and March 2017. Patients had a history of solid tumour in 14 cases, haematological disease in 15 cases and both of them in one case. After a median of 36.5 months (range, 4 to 190) from first neoplasm, patients developed t-AML in 19 cases and t-MDS in 11 cases. Molecular abnormalities were detected in 5 patients, while karyotype aberrations were found in 17 patients. Patients received conventional chemotherapy in 14 cases, azacitidine in 10 cases and both of them in one case. Five patients were submitted to HSCT without previous treatment except for supportive therapy. Results: Seventeen patients obtained sustained CR after SCT, while 8 patients showed resistant or relapsed disease. The remaining five patients died early after SCT. At follow up time (May 2017) 13 patients were alive with a median OS of 48 months (range 3-195), while 17 patients died after a median of 4 months (range 1-27) by relapse mortality in 6 cases and non-relapse mortality in the other 11 patients. Conclusions: Global OS was 43%. After SCT, 72.2% of patients with t-MN maintained a sustained CR. [ABSTRACT FROM AUTHOR]

Background GvHD is one of the major complication after stem cell transplantation affecting transplant-related mortality. Throughout the last years, many serum proteins were been proposed as possible biomarkers for GvHD. Aims We studied the trend of five of the most studied serum proteins to evaluate whether a correlation exists between proteins concentration and post-HSCT outcomes. Materials and methods We measured serum concentration of REG3α, ST2, B-cell activating factor (BAFF), CXCL9 and elafin in a cohort of 77 patients submitted to Hematopoietic allogeneic stem cell transplantation (HSCT) in our department. Blood samples were been collected at baseline, day +30, GvHD onset and GvHD resolution. Results REG3α levels showed an association only with acute GvHD. Elafin and ST2 levels varied according to both acute and chronic GvHD occurrence. BAFF concentration showed an inverse association with acute GvHD development. Interestingly, baseline BAFF and ST2 levels predicted post-HSCT survival. No associations were found for CXCL9. Conclusions Except for CXCL9, the protein levels seem to change according to GvHD development, independently from organ involvement and grading. Pretransplant ST2 and BAFF appeared to be predictors for survival after HSCT. [ABSTRACT FROM AUTHOR]

Background: Allogenic hematopoietic stem cell transplantation (allo-SCT) is the most effective post-remission treatment for adults with high-risk acute lymphoblastic leukemia (ALL). The aim of the study was to analyze results of unmanipulated haploidentical allo-SCT (haplo-SCT) for adults with ALL and to identify prognostic factors. Methods: We performed a retrospective analysis on 208 adults transplanted in EBMT centers from 2007 to 2014. Results: Median age at haplo-SCT was 32 years and median follow-up, 31 months. Forty-four percent of the patients were in first complete remission (CR1). Stem cell source was the bone marrow (BM) for 43% and peripheral blood (PB) for 57% of patients. Myeloablative conditioning (MAC) was used for 66% and reduced intensity regimen (RIC) for 34% of patients. GVHD prophylaxis was based on post-transplant cyclophosphamide (PT-Cy) for 118 (57%) or on antithymocyte-globulin (ATG) for 90 (43%) plus standard prophylaxis. One hundred eighty-four (92%) patients achieved engraftment. Cumulative incidence (CI) of grade II-IV acute-graft-versus-host-disease (GVHD) was 31%, grade III-IV 11%, and chronic GVHD 29%. Non-relapse mortality (NRM) and relapse-incidence (RI) were 32 and 37%, respectively. Overall survival (OS), leukemia-free survival (LFS), and GVHD-free, relapse-free-survival (GRFS) at 3 years were 33, 31, and 26%. For patients in CR1, OS, LFS, and GRFS were 52, 47, and 40%, respectively. Disease status was the main factor associated with transplant outcomes. Use of BM was independently associated with improvement in NRM, acute GVHD, GRFS, LFS, and OS. Conclusions: Unmanipulated haplo-SCT may be considered a valid option for adult patients with high-risk ALL lacking HLA identical donor preferably in early disease status. [ABSTRACT FROM AUTHOR]

Background: Myeloablative (MAC) and reduced-intensity conditioning (RIC) are established approaches for allogeneic stem cell transplantation (SCT) in acute myeloid leukemia (AML). Most deaths after MAC occur within the first 2 years after SCT, while patients surviving leukemia-free for 2 years can expect a favorable long-term outcome. However, there is paucity of data on the long-term outcome (beyond 10 years) and the pattern of late events following RIC due to the relative recent introduction of this approach. Methods: We analyzed long-term outcomes in a cohort of 1423 AML patients, age =50 years, after SCT from HLA-matched siblings, during the years 1997-2005, median follow-up 8.3 years (0.1-17). Results: The 10-year leukemia-free survival (LFS) was 31 % (95CI, 27-35) and 32 % (28-35) after MAC and RIC, respectively (P = 0.57). The 10-year GVHD/ relapse-free survival (GRFS), a surrogate for quality of life was 22 % (18-25) and 21 % (18-24), respectively (P = 0.79). The 10-year non-relapse mortality (NRM) was higher and relapse rate was lower after MAC, throughout the early and late post-transplant course. The 10-year LFS among 584 patients surviving leukemia-free 2 years after SCT was 71 % (65-76) and 73 % (67-78) after MAC and RIC, respectively (P = 0.76). Advanced leukemia at SCT was the major predictor of LFS subsequent to the 2-year landmark. Relapse was the major cause of late death after both regimens; however, NRM and in particular chronic graft-versus-host disease and second cancers were more common causes of late death after MAC. Conclusions: Long-term LFS and GRFS are similar after RIC and MAC. Most events after RIC or MAC occur within the first 2 years after SCT. Patients who are leukemia-free 2 years after SCT can expect similar good subsequent outcome after both approaches. [ABSTRACT FROM AUTHOR]

The article notes the reduction of hospitalization and transfusion support in patients with acute promyelocytic leukemia treated with arsenic trioxide (ATO) plus all-trans retinoic acid (ATRA) compared to chemotherapy plus all-trans retinoic acid. Topic includes recorded data of control cohort treated with chemotherapy plus ATRA, number of patients requiring hospitalization, and number of patients requiring transfusion in induction and consolidation phases.