The Role of Meningioma-1 (Mn1) Gene as Marker for Prognosis and Minimal Residual Disease Monitoring in Acute Myeloid Leukemia: A Concise Review

Molecular markers are necessary for prognostic stratification and monitoring of Minimal Residual Disease (MRD) in Acute Myeloid Leukemia (AML) [1,2]. Cytogenetic aberrations have long been recognized as the most important prognostic variable in AML, and are still the major determinant for post-remission therapy [3]. Unfortunately, only 50-60% of AML patients present an abnormal karyotype at diagnosis, while the remaining cases display a Normal Karyotype (NK). NK AML patients are generally included in an “intermediate risk” prognostic group, that is however characterized by a heterogeneous clinical course. To stratify prognosis of NK AML patients, numerous studies have led, in the last decade, to the introduction of different molecular markers such as FLT3, NPM1, BAALC and CEBPA [4-7]. Still, their use to monitor disease, either defining remission status and detecting relapse as early as possible, is still somehow controversial, due to fluctuations during disease course, low incidence rates in AML and sensitivity of the technologies detecting the single marker [8-10]. These limitations have, to date, precluded a timely and precise quantification of disease in NK AML patients, thus preventing from a complete individualization of post-remission therapy and early treatment in case of impending relapse. In other words, in NK AML it has not been reached the precision achieved in BCR/ABL-positive chronic myeloid leukemia and PML/RAR alpha mutated acute promyelocytic leukemia

Evaluation of CO2-doped blends in single-stage with IHX and parallel compression refrigeration architectures

CO2 is the standard for medium to large-sized commercial applications, as it combines security and low environmental impact. However, it requires the use of advanced and complex cycles. Recently, CO2-doping (the addition of a small quantity of another fluid) has attracted scientific attention, as when CO2 is mixed with fluids with higher critical temperatures, the optimum operation moves to subcritical, providing COP increments in relation to pure-CO2 operation. This work, from a theoretical perspective, evaluates CO2-doping with the fluids R-152a, R-1234yf, R-1234ze(E) and R-1233zd(E) considering the two most used CO2 cycles: the base cycle with an internal heat exchanger (IHX) and the cycle with parallel compression (PC), fractionation taking place. The work analyses the COP improvements for an evaporating level of -10°C and from 10 to 40°C of environment temperature. Predicted maximum COP increments reach up to 5.8% for the IHX cycle and 10.0% for the PC cycle

Predictive value of pretransplantation molecular minimal residual disease assessment by WT1 gene expression in FLT3-positive acute myeloid leukemia

The FMS-like tyrosine kinase 3 (FLT3) mutation in acute myeloid leukemia (AML) is a negative prognostic factor and, in these cases, allogeneic stem cell transplantation (allo-SCT) can represent an important therapeutic option, especially if performed in complete remission (CR). However, it is increasingly clear that not all cytological CRs (cCRs) are the same and that minimal residual disease (MRD) before allo-SCT could have an impact on AML outcome. Unfortunately, FLT3, due its instability of expression, is still not considered a good molecular MRD marker. We analyzed the outcome of allo-SCT in a population of FLT3-positive AML patients according to molecular MRD at the pretransplantation workup, assessed by the quantitative expression evaluation of the panleukemic marker Wilms\u2019 tumor (WT1) gene. Sixty-two consecutive AML FLT3-positive patients received allo-SCT between 2005 and 2016 in our center. The median age at transplantation was 55 years. The quantitative analysis of the WT1 gene expression (bone marrow samples) was available in 54 out of 62 (87%) cases, both at diagnosis (100% overexpressing WT1 with a mean of 9747 \ub1 8064 copies) and before allo-SCT (33 WT1-negative and 21 WT1-positive cases at the pretransplantation workup). Of these cases, 33/54 (61%) were both in cCR and molecular remission (WT1-negative) at the time of transplantation, 13/54 (24%) were in cCR but not in molecular remission (WT1-positive), and 8/54 (15%) showed a cytological evidence of disease (relapsed or refractory). Both post-allo-SCT overall survival (OS) and disease-free survival (DFS) were significantly better in patients who were WT1-negative (WT1 250 copies), with a median OS and DFS not reached in the WT1-negative group and 10.2 and 5.5 months, respectively, in the WT1-positive group (OS log\u2013rank p = 0.0005; hazard ratio [HR] = 3.7, 95% confidence interval [95% CI] = 1.5\u20139; DFS log\u2013rank p = 0.0001; HR = 4.38, 95% CI = 1.9\u201310). Patients with cCR who were WT1-positive had the same negative outcome as those with a cytological evidence of disease. The relapse rate after allo-SCT was 9% (3/33) in pre-allo-SCT WT1-negative cases and 54% (7/13) in WT1-positive cases (p = 0.002). At multivariate analysis, WT1 negativity before allo-SCT and grade <2 acute graft versus host disease were the only independent prognostic factors for improved OS and DFS. These data show that pre-allo-SCT molecular MRD evaluation through WT1 expression is a powerful predictor of posttransplantation outcomes (OS, DFS, relapse rate). Patients with both cCR and a WT1-negative marker before allo-SCT have a very good outcome with very low relapse rate; conversely, patients with positive molecular MRD and refractory/relapsed patients have a negative outcome. The WT1 MRD stratification in FLT3-positive AML is a valuable tool with which to identify patients who are at high risk of relapse and that could be considered from post-allo-SCT prophylaxis with FLT3 inhibitors or other strategies (donor lymphocyte infusion, tapering of immunosuppression, azacitidine). \ua9 2017 ISEH - International Society for Experimental Hematolog

BCR::ABL1 levels at first month after TKI discontinuation predict subsequent maintenance of treatment-free remission: A study from the “GRUPPO TRIVENETO LMC”

We analyzed BCR::ABL1 expression at stop and in the first month after discontinuation in 168 chronic myeloid leukemia patients who stopped imatinib or 2nd generation tyrosine kinase inhibitors (2G-TKIs) while in sustained deep molecular response. Patients were divided among those who maintained response (group 1, n = 123) and those who lost major molecular response (group 2, n = 45). Mean BCR::ABL1 RNA levels 1 month after discontinuation were higher in group 2 than in group 1 (p = 0.0005) and the difference was more evident 2 months after stop (p < 0.0001). The same trend was found both for imatinib and 2G-TKIs. A receiver operating characteristic (ROC) analysis to determine a threshold value of BCR::ABL1 at 1 month after discontinuation identified a cut-off value of 0.0051%, with 92.2% specificity, 31.7% sensitivity and a likelihood ratio of 4.087

Empathy at Play:Embodying Posthuman Subjectivities in Gaming

In this article, we address the need for a posthuman account of the relationship between the avatar and player. We draw on a particular line of posthumanist theory associated closely with the work of Karen Barad, Rosi Braidotti and N. Katherine Hayles that suggests a constantly permeable, fluid and extended subjectivity, displacing the boundaries between human and other. In doing so, we propose a posthuman concept of empathy in gameplay, and we apply this concept to data from the first author’s 18-month ethnographic field notes of gameplay in the MMORPG World of Warcraft. Exploring these data through our analysis of posthuman empathy, we demonstrate the entanglement of avatar–player, machine–human relationship. We show how empathy allows us to understand this relationship as constantly negotiated and in process, producing visceral reactions in the intra-connected avatar–player subject as well as moments of co-produced in-game action that require ‘affective matching’ between subjective and embodied experiences. We argue that this account of the avatar–player relationship extends research in game culture, providing a horizontal, non-hierarchical discussion of its most necessary interaction

Children and objects: affection and infection

This paper considers young children’s (aged 3–5 years) relations with objects, and in particular objects that are brought from home to school. We begin by considering the place of objects within early years classrooms and their relationship to children’s education before considering why some objects are often separated from their owners on entry to the classroom. We suggest that the ‘arrest’ of objects is as a consequence of them being understood as ‘infecting’ specific perceptions or constructs of young children. We further suggest that a focus on the dichotomy between affection/infection for and of certain objects may offer new possibilities for seeing and engaging with children, thus expanding the narrow imaginaries of children that are coded in developmental psychology, UK early years education policy and classroom practice

Acute rhabdomyolysis and delayed pericardial effusion in an Italian patient with Ebola virus disease : a case report

Background: During the 2013-2016 West Africa Ebola virus disease (EVD) epidemic, some EVD patients, mostly health care workers, were evacuated to Europe and the USA. Case presentation: In May 2015, a 37-year old male nurse contracted Ebola virus disease in Sierra Leone. After Ebola virus detection in plasma, he was medically-evacuated to Italy. At admission, rhabdomyolysis was clinically and laboratory-diagnosed and was treated with aggressive hydration, oral favipiravir and intravenous investigational monoclonal antibodies against Ebola virus. The recovery clinical phase was complicated by a febrile thrombocytopenic syndrome with pericardial effusion treated with corticosteroids for 10days and indomethacin for 2months. No evidence of recurrence is reported. Conclusions: A febrile thrombocytopenic syndrome with pericardial effusion during the recovery phase of EVD appears to be uncommon. Clinical improvement with corticosteroid treatment suggests that an immune-mediated mechanism contributed to the pericardial effusion

Descrizione di un caso d porpora trombocitopenica autoimmune in gravidanza

La porpora trombocitopenica autoimmune \ue8 una patologia rara e grave che pu\uf2 insorgere in gravidanza. La paziente \ue8 stata sottoposta a terapia cortisonica e con immunoglobuline sclavo in preparazione all'intervento di taglio cesareo elettivo.In mancanza di un recupero dei valori delle piastrine, sono state somministrate tre unit\ue0 di piastrine da diaferesi, da unico donatore. Eseguito taglio cesareo elettivo alla XXXIV settimana, non si sono avute complicazioni del decorso post operatorio della paziente. La neonata del peso 2550gr. ha avuto un normale outcome neonatale