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There is little evidence about the origin of the phrase una faccia, una razza (one face, one race). However, its use signifies numerous shared elements in the cultures of Italy and Greece. In both countries, adult education emerged within the critical paradigm whereas vocationalism is currently the leading force of adult education policy development. The purpose of this article is to discuss the paths of adult education policy evolution over the last 40 years in both countries. Acknowledging Europeanization, neoliberalism, and vocationalism as the forces of policy change, the article provides a detailed critical review, a synthesis, and a proposal about future steps in adult education policy.

The contribution describes a study on the organizational devices and the professional development programs carried out at the Teaching and Learning Center (TLC) of the University of Siena and at the Teaching and Learning Lab (TLL) of the University of Macerata. The focus is on systemic actions capable to elicit innovation at an organizational level, starting from the work of the institutional centers for research, professional training, and digital enhanced learning embedded in the university. In the final paragraph, future developmental trajectories for constituting an inter-universities network of TLCs are discussed.

Research around learning community models often shows a structured and defined model to follow with the underlying assumption being if the steps are followed, the results will come. The model we offer in this paper is rather counter-cultural as it was not a specific process or practice we followed; rather, we found ourselves in a highly engaging, safe, kind, and productive learning community unlike most we have encountered in academia. We asked ourselves, "Why?" and engaged in reflection, questions, and research to define our unique community. Six themes emerged that form our ecological learning community; these themes are in motion, intertwined, and co-dependent on one another. Our model is not linear, instead, it is fluid and organic, moving from firm boundaries to more porous edges or shapes that respond to the needs of the group and communities around us to create an inclusive environment. The six themes are: 1) organic trust, safety, and belonging, 2) shared collective vision; 3) cultural humility; 4) inclusion--a commitment to diversity of perspectives; 5) shared leadership; and 6) practices in alignment with values. We offer suggestions for practices for learning communities that similarly aim to be responsive and adaptive.

Research in inclusive education reveals multiple studies that explore the efforts of individual stakeholders to create an equitable educational experience for students with disabilities. However, these individual efforts are often examined discretely, compartmentalising the contributions of various stakeholders. As a consequence, the complex interplay between these contributions has not been fully explored, with the capacity for a rich network of support being assumed rather than explicitly constructed. This report draws on the personal reflections of nine academics in the field of inclusive education from Australia, Canada, Germany, Greece, Italy, and Switzerland. Serving as both contributors and participants, this study draws together their personal interpretations and their expertise regarding the value of collective and collaborative inclusive education. Inductive thematic analysis of participant reflections yielded the view that stakeholders working together within an educational setting, offers more effective and appropriate opportunities to support learners with additional needs.

The contribution describes a study on the organizational devices and the professional development programs carried out at the Teaching and Learning Center (TLC) of the University of Siena and at the Teaching and Learning Lab (TLL) of the University of Macerata. The focus is on systemic actions capable to elicit innovation at an organizational level, starting from the work of the institutional centers for research, professional training, and digital enhanced learning embedded in the university. In the final paragraph, future developmental trajectories for constituting an inter-universities network of TLCs are discussed.

Neoplastic plasma cells (PCs) proliferation at anatomic sites dislocated from the bone marrow (BM) or their contiguous growth from osseous lesions that disrupt the cortical bone is termed extramedullary multiple myeloma (EMD). EMD still remains challenging from a therapeutic and biological perspective. Pathogenesis has not been completely clarified, and it is generally associated with high-risk cytogenetics (HRCAs). In order to emphasize the clinical and biochemical complexity of this disease, we have decided to describe the case of a patient affected by relapsed-refractory (RR) EMD, which presented as para-osseous plasmacytoma with a bi-phenotypical immunoglobulin (Ig) component and lately relapsed as soft-tissue plasmacytoma with a total immunophenotype switch. We have also hypothesized a correlation between Ig patterns and prognosis and suggested the possible inclusion of these biochemical features in the general risk assessment. [ABSTRACT FROM AUTHOR]

The article analyzes the learning paths, organizational devices, and system actions taken within the Teaching & Learning Center research and training facility at the University of Siena.

Background: Chronic myeloid leukemia is a hematological malignancy characterized by the abnormal proliferation of leukemic cells. Despite significant progress with tyrosine kinase inhibitors, such as Dasatinib, resistance remains a challenge. The aim of the present study was to investigate the potential of Selinexor, an Exportin-1 inhibitor, to improve TKI effectiveness on CML. Methods: Human CML cell lines (LAMA84 and K562) were treated with Selinexor, Dasatinib, or their combination. Apoptosis, mitochondrial membrane potential, and mitochondrial mass were assessed using flow cytometry. Real-time RT-PCR was used to evaluate the expression of genes related to mitochondrial function. Western blot and confocal microscopy examined PINK and heme oxygenase-1 (HO-1) protein levels. Results: Selinexor induced apoptosis and mitochondrial depolarization in CML cell lines, reducing cell viability. The Dasatinib/Selinexor combination further enhanced cytotoxicity, modified mitochondrial fitness, and downregulated HO-1 nuclear translocation, which has been associated with drug resistance in different models. Conclusions: In conclusion, this study suggests that Dasatinib/Selinexor could be a promising therapeutic strategy for CML, providing new insights for new targeted therapies. [ABSTRACT FROM AUTHOR]

Although the therapeutic landscape for multiple myeloma (MM) has expanded, the disease always tends to relapse. In an attempt to obtain deep and durable responses, each relapse requires the use of a new strategy. In recent years, new treatment options have emerged, even for heavily treated patients. Novel, well-tolerated, and highly effective therapies in the relapsed/refractory (RRMM) setting currently represent a real hope. Belantamab mafodotin (BLENREP™) is a first-in-class monoclonal antibody-drug conjugate whose target is B-cell maturation antigen conjugated to the cytotoxic microtubule inhibitor monomethyl auristatin F. Here, we present two cases of heavily pre-treated RRMM patients that were favorably treated with belantamab mafodotin, obtaining at least a partial response. Treatment was well tolerated and is ongoing. This is a rare report on real life clinical use of belantamab mafodotin outside of controlled clinical trials and provides information on efficacy and safety of this anti-myeloma new class of drugs. [ABSTRACT FROM AUTHOR]

Data on the efficacy of high-dose chemotherapy and autologous stem cell transplantation (ASCT) for classical Hodgkin lymphoma (cHL) patients who failed a PET-driven first-line therapy are limited. We retrospectively evaluated 220 adult cHL patients who underwent ASCT from 2009 to 2021 at 11 centers in Italy. Overall, 49.5% had refractory disease, 23.2% relapsed < 12 and 27.3% ≥12 months from the end of first-line chemotherapy. The 3-year progression-free survival (PFS) and overall survival (OS) were 73.8% and 89.4%. In univariable analysis for PFS events PET-2+ (HR 2.69, p =.001), anemia (HR 2.22, p =.019), refractory disease (HR 1.76, p =.045), less than CR before ASCT (HR 3.24, p <.001) and >2 lines of salvage therapy (HR 2.52; p =.004) were associated with a higher risk of failure after ASCT. In multivariable analysis, >2 lines of salvage therapy (HR 3.28, p =.004) and RT before ASCT (HR 3.00, p = 0.041) retained significance. ASCT is an effective salvage approach for cHL patients treated in the era of PET-adapted therapies. [ABSTRACT FROM AUTHOR]

Previous research has identified the importance of teacher attitudes and self-efficacy in supporting inclusive education. This study involved a multi-national exploration of a further dimension of inclusive education, collective efficacy, through the testing of a new tool, the Teacher Efficacy for Inclusive Practice-Collective (TEIP-C) Scale. The study also aimed to investigate whether teacher attitudes, self-efficacy, collective efficacy and intention to teach in inclusive classrooms differ across countries. Participants included 1,523 teachers from Canada, Greece, Italy and Switzerland. Results suggested a two-factor structure for the TEIP-C, Engagement, and Inclusive Pedagogies, with strong internal consistency for the scale. Several differences across countries were identified, with teachers from Italy reporting more positive attitudes towards inclusion and a greater intention to teach in inclusive classrooms. Implications of the study in terms of further strengthening inclusive practice are discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: Hodgkin Lymphoma (HL) has a prognostic assessment often relying on PET scans after two ABVD treatment cycles (PET-2). This retrospective, observational, single–center, real-life study, evaluated 212 newly diagnosed HL patients, highlighting the role of IgM levels at diagnosis. IgM ≤ 50 mg/dL at baseline emerges as an independent predictor for progression-free survival in classic HL, offering an early and crucial prognostic marker. Additionally, the combined factors of IgM ≤ 50 mg/dL and the presence of a large nodal mass (<7 cm) serve as predictors of outcomes in classic HL, emphasizing the importance of these parameters in understanding and managing the disease above all in cases with unclear PET-2 and guaranteeing the best of care for the patients with an improved outcome. Hodgkin Lymphoma (HL) is characterized by an inflammatory background in which the reactive myeloid cells may exert an immune-suppressive effect related to the progression of the disease. Immunoglobulin M is the first antibody isotype produced during an immune response, which also plays an immunoregulatory role. Therefore, we investigated if, as a surrogate of defective B cell function, it could have any clinical impact on prognosis. In this retrospective, observational, single–center study, we evaluated 212 newly diagnosed HL patients, including 132 advanced-stage. A 50 mg/dL level of IgM at baseline resulted in 84.1% sensitivity and 45.5% specificity for predicting a complete response in the whole cohort (area under curve (AUC) = 0.62, p = 0.013). In multivariate analysis, baseline IgM ≤ 50 mg/dL and the presence of a large nodal mass (<7 cm) were independent variables able to predict the clinical outcome, while, after two cycles of treatment, IgM ≤ 50 mg/dL at baseline and PET-2 status were independent predictors of PFS. The amount of IgM at diagnosis is a valuable prognostic factor much earlier than PET-2, and it can also provide information for PET-2-negative patients. This can help to identify different HL classes at risk of treatment failure at baseline. [ABSTRACT FROM AUTHOR]

Background: Managing SARS‐CoV‐2 infection in frail and immunosuppressed patients still represents an open challenge, but, starting from the phase 3 PROVENT study, prophylaxis with tixagevimab‐cilgavimab has improved the approach in this category of patients, guaranteeing a better outcome and inferior mortality. Real‐life data in a heterogeneous cohort are few. Methods: The aim of this study is to evaluate the benefit of prophylaxis with tixagevimab‐cilgavimab in a cohort of 202 patients affected by different hematological diseases (lymphoproliferative, myeloproliferative, autoimmune, patients recently receiving a bone marrow transplant), active (with ongoing treatment), or in watch‐and‐wait strategy, followed in our center, during a median follow‐up of 249 (45‐325) days. Results: An incidence of 44 breakthrough infections (21.8%) is reported, with no treatment‐related adverse effects. Age ≥70 years, ongoing treatment (above all with monoclonal antibodies), baseline lymphoproliferative disorders, and prior virus exposure are identified as risk factors related to subsequent infection (p < 0.05). Moreover, the incidence is higher in low/nonresponse to prior vaccination (p =.002). Patients treated with tixagevimab‐cilgavimab had a mild course of the infection and a reduction of the duration compared with preprophylaxis infection (11 vs. 15 days, p <.001). The concurrent treatment with anti‐CD20 monoclonal antibodies and B–non‐Hodgkin lymphoma still confers a higher duration of infection despite prophylaxis. No deaths attributable to the infection occurred. Conclusion: Prophylaxis treatment seems to be a valid and safe strategy, although not preventing breakthrough infection, but the severe complications associated with the infection and the possible delays in administering lifesaving therapies from long positivity. The use of tixagevimab‐cilgavimab improved the management of immunocompromised patients with a high risk of severe SARS‐CoV‐2 disease. In a real‐world setting, it confirmed its role not only in preventing the occurrence of breakthrough infection, but also, above all, avoiding the severe complications associated and reducing the total days of positivity. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) are a subset of heterogeneous, non-hematopoietic fibroblast-like cells which play important roles in tissue repair, inflammation, and immune modulation. MSCs residing in the bone marrow microenvironment (BMME) functionally interact with hematopoietic stem progenitor cells regulating hematopoiesis. However, MSCs have also emerged in recent years as key regulators of the tumor microenvironment. Indeed, they are now considered active players in the pathophysiology of hematologic malignancies rather than passive bystanders in the hematopoietic microenvironment. Once a malignant event occurs, the BMME acquires cellular, molecular, and epigenetic abnormalities affecting tumor growth and progression. In this context, MSC behavior is affected by signals coming from cancer cells. Furthermore, it has been shown that stromal cells themselves play a major role in several hematological malignancies' pathogenesis. This bidirectional crosstalk creates a functional tumor niche unit wherein tumor cells acquire a selective advantage over their normal counterparts and are protected from drug treatment. It is therefore of critical importance to unveil the underlying mechanisms which activate a protumor phenotype of MSCs for defining the unmasked vulnerabilities of hematological cancer cells which could be pharmacologically exploited to disrupt tumor/MSC coupling. The present review focuses on the current knowledge about MSC dysfunction mechanisms in the BMME of hematological cancers, sustaining tumor growth, immune escape, and cancer progression. [ABSTRACT FROM AUTHOR]

Background: Gaucher disease (GD) is a rare autosomal recessive inherited disorder caused by the lysosomal enzyme acid β‐glucosidase deficiency. Many patients experience a critical delay in the diagnosis of up to 8–10 years due to its rarity and variability in signs and symptoms, with the consultation of several specialists. Patients and Methods: This prospective observational study analyzed the prevalence of GD in 600 patients with monoclonal gammopathy of uncertain significance (MGUS) from January 2018 until February 2022. Results: The mean age of participants was 66 years, with a mean monoclonal component of 0.58 g/dL. In 433 MGUS patients with available data, anemia (hemoglobin level < 10 g/dL) was present in 31 patients (7%), and thrombocytopenia (platelet count <100.000/mm3) in 24 (5.5%). Of 600 MGUS patients tested for acid β‐glucosidase enzyme activity, 7 patients (1.2%) had activity below 2.5 nmol/h/mL. In comparison, GBA gene analysis was executed in 110 patients. It revealed 4 patients (0.7%) affected by GD (3 patients with compound heterozygous mutation and 1 with homozygous mutation), with a prevalence of 1 every 150 MGUS patients. Furthermore, 12 out of the remaining 106 evaluated patients (11%) were carriers of a single heterozygous mutation while having regular enzyme activity. Conclusions: The clinical heterogeneity of GD and frequent lack of awareness among physicians often lead to diagnostic delays and severe clinical manifestations. The role of MGUS in the presence of at least one clinical sign, such as low platelet count, organomegaly, bone pain, or bleeding tendency, could aid in initiating GD screening with DBS, thus reducing the period between symptom onset and the diagnosis of this rare disease. [ABSTRACT FROM AUTHOR]

Ecological interactions are fundamental at the cellular scale, addressing the possibility of a description of cellular systems that uses language and principles of ecology. In this work, we use a minimal ecological approach that encompasses growth, adaptation and survival of cell populations to model cell metabolisms and competition under energetic constraints. As a proof-of-concept, we apply this general formulation to study the dynamics of the onset of a specific blood cancer—called Multiple Myeloma. We show that a minimal model describing antagonist cell populations competing for limited resources, as regulated by microenvironmental factors and internal cellular structures, reproduces patterns of Multiple Myeloma evolution, due to the uncontrolled proliferation of cancerous plasma cells within the bone marrow. The model is characterized by a class of regime shifts to more dissipative states for selectively advantaged malignant plasma cells, reflecting a breakdown of self-regulation in the bone marrow. The transition times obtained from the simulations range from years to decades consistently with clinical observations of survival times of patients. This irreversible dynamical behavior represents a possible description of the incurable nature of myelomas based on the ecological interactions between plasma cells and the microenvironment, embedded in a larger complex system. The use of ATP equivalent energy units in defining stocks and flows is a key to constructing an ecological model which reproduces the onset of myelomas as transitions between states of a system which reflects the energetics of plasma cells. This work provides a basis to construct more complex models representing myelomas, which can be compared with model ecosystems. Author summary: Ecological interactions at the scale of cell populations are important to understand the emergent behavior of complex biological systems as diseases. Despite the extensive knowledge of the molecular and cellular details of biomedical systems, understanding the mechanisms behind the onset of Multiple Myeloma and predicting its dynamic evolution is a challenge. For diseases characterized by recurrent patterns and non-genetic plasticity, it is not possible to eradicate the mechanism that sustains cancer onset and evolution, namely they are defined as incurable. This mechanism is not typical of blood cancer itself, being a general emergent behavior of ecological systems as determined by the complex interactions between system's elements and the environment. Unfolding the role of the competitive interaction between normal, cancerous cell populations and the micro-environment by quantifying the energetic constraints operating on them is of key relevance. Here, adopting an energetic approach, we show that it is possible to reproduce stylized patterns of Multiple Myeloma onset by means of a minimal stock-flow ecological model of competing normal and malignant plasma cell populations. Our results suggest the potential of this general approach to build more detailed models of Multiple Myeloma, as well as to study biological systems and diseases. [ABSTRACT FROM AUTHOR]

Multiple myeloma is a chronic hematologic malignancy that obstinately tends to relapse. Basic research has made giant strides in better characterizing the molecular mechanisms of the disease. The results have led to the manufacturing of new, revolutionary drugs which have been widely tested in clinical trials. These drugs have been approved and are now part of the therapeutic armamentarium. As a consequence, it is essential to combine what we know from clinical trials with real-world data in order to improve therapeutic strategies. Starting with this premise, our review aims to describe the currently employed regimens in multiple myeloma and compare clinical trials with real-life experiences. We also intend to put a spotlight on promising therapies such as T-cell engagers and chimeric antigen receptor T-cells (CAR-T) which are proving to be effective in changing the course of advanced-stage disease. [ABSTRACT FROM AUTHOR]

Blinatumomab is a bispecific anti-CD3 and anti-CD19 antibody that acts as a T-cell engager: by binding CD19+ lymphoblasts, blinatumomab recruits cytotoxic CD3+ T-lymphocytes to target the cancer cells. Here we describe seven different patients affected by B-cell precursor acute lymphoblastic leukemia (Bcp-ALL) and treated with blinatumomab, on which we evaluated the potential association between the amount of different T-cells subsets and deep molecular response after the first cycle, identified as a complete remission in the absence of minimal residual disease (CR/MRD). The immune-system effector cells studied were CD3+, CD4+ effector memory (T4-EM), CD8+ effector memory (T8-EM), and T-regulatory (T-reg) lymphocytes, and myeloid-derived suppressor cells (MDSC). Measurements were performed in the peripheral blood using flow cytometry of the peripheral blood at baseline andafter the firstcycle of blinatumomab. The first results showthat patients with a higher proportion of baseline T-lymphocytes achieved MRD negativitymore frequently with no statistically significant difference (p=0.06) and without differences in the subpopulation count following the first treatment. These extremely preliminary data could potentially pave the way for future studies, including larger and less heterogeneous cohorts, in order to assess the T-cell kinetics in a specific set of patients with potential synergy effects in targeting myeloid-derived suppressor cells (MDSC), commonly known to have an immune evasionmechanism in Bcp-ALL. [ABSTRACT FROM AUTHOR]

Simple Summary: For a few years, lenalidomide plus dexamethasone (Len/Dex) has become a new standard of care for newly diagnosed multiple myeloma (NDMM) patients who are not eligible for autologous stem cell transplantation. The FIRST trial showed that continuous therapy with Len/Dex is superior in progression-free survival (PFS) and overall survival (OS) compared to fixed treatment or triplet, leading to approval for NDMM. The knowledge of the safety and efficacy of Len/Dex in frail and ultra-frail patients is limited. This study evaluates the Len/Dex combination, correlating it with the prognostic impact of different variables on PFS and OS. Our real-world data report that an elderly and frail population, rarely included in randomized clinical trials, may benefit from Len/Dex combination, with an incidence of adverse events that is inferior to pivotal trials. Thus, the oral and self-administering outpatient Len/Dex scheme is a considerable treatment choice in patients with high ECOG or age >75 years old. Based on the results obtained in clinical trials, the use of the combination of lenalidomide and dexamethasone (Len/Dex) has become a potential therapeutic choice for newly diagnosed multiple myeloma (NDMM) ineligible for autologous stem cell transplantation. This study evaluated 89 frail NDMM patients treated with first-line oral association. At the last follow-up, 34 out of 89 patients (38.2%) were alive, and 22 were still in treatment with Len/Dex. Among 73 evaluable patients who received at least two cycles, the overall response rate was 71% (N = 52). The disease control rate, defined as any level of clinical response to therapy, occurred in 71 patients (97%). We reported one or more adverse events of grade 3 or 4 (G3/4) in 65.2% (N = 58) of patients, with a prevalence of hematological toxicity (24 patients), leading to an overall discontinuation of treatment in two cases. In univariate analysis, high ISS, high serum β2-microglobulin, and creatinine clearance <30 mL/min negatively impact OS, while the depth of response positively impacts OS. Moreover, G3-4 anemia, ISS, frailty score, and ECOG negatively impacts PFS. In conclusion, elderly and more frail patients benefit from the Len/Dex combination also in the era of monoclonal antibodies, ensuring an increased PFS and OS in patients where the therapeutic choice is often limited and usually not very effective. [ABSTRACT FROM AUTHOR]

Pars plana vitrectomy is today a common first-line procedure for treatment of rhegmatogenous retinal detachment (RRD). Removal or preservation of the natural lens at the time of vitrectomy is associated with both advantages and disadvantages. The combination of cataract extraction (i.e., phacoemulsification) with pars plana vitrectomy (PPVc) enhances visualization of the peripheral retina and the surgical management of the vitreous base. However, PPVc prolongs the surgical time and is associated with iatrogenic loss of the accommodation function in younger patients, possible postoperative anisometropia, and unexpected refractive results. Performance of pars plana vitrectomy alone (PPVa) requires good technical skills to minimize the risk of lens damage, and quickens cataract development. We retrieved all recent papers that directly compared PPVc and PPVa using parameters that we consider essential when choosing between the two procedures (the success rate of anatomical RRD repair, postoperative refractive error, intra- and postoperative complications, and costs). PPVa and PPVc were generally comparable in terms of RRD anatomical repair. PPVc was associated with fewer intraoperative, but more postoperative, complications. Macula-off RRD PPVc treatment was often associated with undesirable myopic refractive error. PPVa followed by phacoemulsification was the most expensive procedure. [ABSTRACT FROM AUTHOR]

The Lugano classification for response assessment in lymphoma recommends the use of the 5‐point‐scale Deauville Score (DS) to assess response evaluation of end‐of‐treatment FDG‐PET/CT (eotPET) in Hodgkin Lymphoma (HL); nevertheless, there is a paucity of data on its accuracy and reproducibility. We focus here on the cohort of advanced stage IIb‐IV HL patients enrolled in the HD0607 clinical trial (NCT identifier 00795613) that having had a negative interim PET performed 6 cycles of ABVD (Doxorubicin, Vinblastine, Vincristine and Dacarbazine) and then performed an eotPET. Negative patients were randomized to radiotherapy and no further treatment while positive patients were treated based on local policies. eotPET was re‐evaluated independently by two readers evaluated and progression free survival was analysed (PFS). eotPET of 254 patients were analysed. The median follow‐up was 43 months. The best receiver operator characteristics cut‐off values to distinguish positive and negative patients was 4. The area‐under‐the‐curve was 0.81 (95%CI, 0.70–0.91). Three‐years PFS was 0.95 (95% CI 0.90–0.97) in eotPET negative and 0.22 (95% CI 0.11–0.43) in eotPET positive. DS demonstrated a good reproducibility of positivity/negativity between the readers consensus and local site evaluation where the agreement occurred on 95.0% of patients. The present study demonstrates that eotPET is an accurate tool to predict treatment outcome in HL and confirms the appropriateness of the Lugano classification for eotPET evaluation. [ABSTRACT FROM AUTHOR]

The concomitant presence of Castleman disease (CD) with other hematological pathology is an event described in the literature with increasing frequency, able to modify the diagnostic and curative approach in such patients. Very few studies in the literature describe the association of CD with concomitant neoplastic diseases; the most frequent are Kaposi's sarcomas (especially in HIV and human herpes virus-8-positive patients) and lymphoproliferative disorders, such as lymphomas. Instead, since the association with plasma cell diseases such as multiple myeloma and plasmacytoma is infrequent, there is a lack of literature. This manuscript aimed to revise the literature by describing a rare case of CD and plasmacytoma and attempting to explain the underlying triggering mechanisms. [ABSTRACT FROM AUTHOR]

Aggressive SM + AML has limited therapeutic options. Even a strong combination of decitabine–venetoclax–midostaurin has a transient effect on AML and a mitigated effect on SM. Larger series are required to identify the best therapeutic strategy. [ABSTRACT FROM AUTHOR]

Summary: Little is known of the course of COVID‐19 and the antibody response to infection or vaccination in patients with hairy‐cell leukaemia (HCL). Among a total of 58 HCL cases we studied in these regards, 37 unvaccinated patients, mostly enjoying a relatively long period free from anti‐leukaemic treatment, developed COVID‐19 between March 2020 and December 2021 with a usually favourable outcome (fatality rate: 5/37, 14%); however, active leukaemia, older age and more comorbidities were associated with a worse course. Postinfection (n = 11 cases) and postvaccination (n = 28) seroconversion consistently developed, except after recent anti‐CD20 or venetoclax therapy, correlating with perivaccine B‐cell count. Vaccination appeared to protect from severe COVID‐19 in 11 patients with breakthrough infection. [ABSTRACT FROM AUTHOR]

Research in inclusive education reveals multiple studies that explore the efforts of individual stakeholders to create an equitable educational experience for students with disabilities. However, these individual efforts are often examined discretely, compartmentalising the contributions of various stakeholders. As a consequence, the complex interplay between these contributions has not been fully explored, with the capacity for a rich network of support being assumed rather than explicitly constructed. This report draws on the personal reflections of nine academics in the field of inclusive education from Australia, Canada, Germany, Greece, Italy, and Switzerland. Serving as both contributors and participants, this study draws together their personal interpretations and their expertise regarding the value of collective and collaborative inclusive education. Inductive thematic analysis of participant reflections yielded the view that stakeholders working together within an educational setting, offers more effective and appropriate opportunities to support learners with additional needs. [ABSTRACT FROM AUTHOR]

Metabolic changes of malignant plasma cells (PCs) and adaptation to tumour microenvironment represent one of the hallmarks of multiple myeloma (MM). We previously showed that MM mesenchymal stromal cells are more glycolytic and produce more lactate than healthy counterpart. Hence, we aimed to explore the impact of high lactate concentration on metabolism of tumour PCs and its impact on the efficacy of proteasome inhibitors (PIs). Lactate concentration was performed by colorimetric assay on MM patient's sera. The metabolism of MM cell treated with lactate was assessed by seahorse and real time Polymerase Chain Reaction (PCR). Cytometry was used to evaluate mitochondrial reactive oxygen species (mROS), apoptosis and mitochondrial depolarization. Lactate concentration resulted increased in MM patient's sera. Therefore, PCs were treated with lactate and we observed an increase of oxidative phosphorylation‐related genes, mROS and oxygen consumption rate. Lactate supplementation exhibited a significant reduction in cell proliferation and less responsive to PIs. These data were confirmed by pharmacological inhibition of monocarboxylate transporter 1 (MCT1) by AZD3965 which was able to overcame metabolic protective effect of lactate against PIs. Consistently, high levels of circulating lactate caused expansion of Treg and monocytic myeloid derived suppressor cells and such effect was significantly reduced by AZD3965. Overall, these findings showed that targeting lactate trafficking in TME inhibits metabolic rewiring of tumour PCs, lactate‐dependent immune evasion and thus improving therapy efficacy. [ABSTRACT FROM AUTHOR]

Introduction: Patients with multiple myeloma (MM) frequently reported immune impairment with an increased risk for infection-related mortality. We aimed to evaluate the immune response in MM patients vaccinated for SARS-CoV-2 during active treatment. Methods: We enrolled 158 patients affected by active MM or smoldering MM (SMM) and 40 healthy subjects. All subjects received 2 or 3 doses of the BNT162b2 (Pfizer/BioNTech) vaccine, and the anti-spike IgG values were evaluated after every dose. We applied the Propensity Score Matching (PSM) as a consequence of the limited sample size and its heterogeneity to adjust for differences in baseline clinical variables between MM patients who achieved or not a vaccine response after 2 or 3 doses. Results: At 30 days from the second dose, the median antibodies level inMM was 25.2 AU/mL, lower than in SMM and in the control group. The same results were confirmed after the third dose, with lower median anti-spike IgG levels in MM, compared to SMM and control group. Following PSM, lack of response to SARSCoV-2 complete vaccination plus boost was associated with age more than 70 years old and use of high-dose of steroids. We failed to identify an association between specific treatment types and reduced vaccine response. The use of prophylaxis with tixagevimab/cilgavimab for 40 non-responder patients after 3 doses of vaccine has proven to be an effective and safe approach in reducing the risk of serious illness in the event of a breakthrough SARS-CoV-2 infection, faced with a mild symptomatic course, and in providing protection instead of longterm humoral immune vaccine responses. Following PSM, only the high-risk cytogenetic abnormalities were associated with an increased risk of developing a breakthrough SARS-CoV-2 infection. Conclusion: Monitoring the immune response is fundamental in MM patients that remain highly vulnerable to SARS-CoV-2 despite the vaccine. The use of prophylaxis with tixagevimab/cilgavimab can guarantee better protection from the severe form of the disease. [ABSTRACT FROM AUTHOR]

Among the myeloproliferative diseases, myelofibrosis is a widely heterogeneous entity characterized by a highly variable prognosis. In this context, several prognostic models have been proposed to categorize these patients appropriately. Identifying who deserves more invasive treatments, such as bone marrow transplantation, is a critical clinical need. Age, complete blood count (above all, hemoglobin value), constitutional symptoms, driver mutations, and blast cells have always represented the milestones of the leading models still used worldwide (IPSS, DIPSS, MYSEC-PM). Recently, the advent of new diagnostic techniques (among all, next-generation sequencing) and the extensive use of JAK inhibitor drugs have allowed the development and validation of new models (MIPSS-70 and version 2.0, GIPSS, RR6), which are continuously updated. Finally, the new frontier of artificial intelligence promises to build models capable of drawing an overall survival perspective for each patient. This review aims to collect and summarize the existing standard prognostic models in myelofibrosis and examine the setting where each of these finds its best application. [ABSTRACT FROM AUTHOR]