Noise reduction in muon tomography for detecting high density objects

The muon tomography technique, based on multiple Coulomb scattering of cosmic ray muons, has been proposed as a tool to detect the presence of high density objects inside closed volumes. In this paper a new and innovative method is presented to handle the density fluctuations (noise) of reconstructed images, a well known problem of this technique. The effectiveness of our method is evaluated using experimental data obtained with a muon tomography prototype located at the Legnaro National Laboratories (LNL) of the Istituto Nazionale di Fisica Nucleare (INFN). The results reported in this paper, obtained with real cosmic ray data, show that with appropriate image filtering and muon momentum classification, the muon tomography technique can detect high density materials, such as lead, albeit surrounded by light or medium density material, in short times. A comparison with algorithms published in literature is also presented

A multicenter retrospective clinical study of CD5/CD10-negative chronic B cell leukemias.

CD5-negative chronic B cell lymphoproliferative disorders in leukemic phase (B-CLPD) are heterogeneous and relatively uncommon pathologies that often lack a histopathological definition because of the absence of accessible pathological tissue. We describe the clinical features and evolution-related variables of 156 patients with CD5/CD10-negative B-CLPD (median age 66 years, range 25-86). The median follow-up was 51 months (range 6-216), and overall 3- and 5-year survival was respectively 87 and 76%; 50 patients needed therapy at diagnosis, 56 during follow-up, and 50 remained untreated until the last control. A combined clinical, histological, cytomorphological, immunophenotypical, and cytogenetic diagnostic approach allowed the complete classification of only a minority of patients as being affected by splenic marginal zone or lymphoplasmacytic lymphoma; the majority of cases remained unclassifiable. Multivariate analysis showed that the clinicohematological variables adversely related to overall survival were serum LDH levels and age, whereas high serum LDH levels, hemoglobin levels of <11 g/dl, and splenomegaly related to treatment-free time (in "wait and see" cases); only splenomegaly related to time to progression (in treated patients). In conclusion, our retrospective study describes the clinical features and variables related to evolution in a large group of patients with CD5/CD10-negative chronic B-cell lymphoid leukemias and underlines the fact that a probable lymphoplasmacytic or marginal zone normal cell origin can be supposed in such leukemic forms, but never surely demonstrated

Peripheral T-cell lymphoma unspecified (PTCL-U): a new prognostic model from a retrospective multicentric clinical study

To assess the prognosis of peripheral T-cell lymphoma unspecified, we retrospectively analyzed 385 cases fulfilling the criteria defined by the World Health Organization classification. Factors associated with a worse overall survival (OS) in a univariate analysis were age older than 60 years (P=.0002), equal to or more than 2 extranodal sites (P=.0002), lactic dehydrogenase (LDH) value at normal levels or above (P<.0001), performance status (PS) equal to or more than 2 (Pless than or equal to.0001), stage III or higher (P=.0001), and bone marrow involvement (P=.0001). Multivariate analysis showed that age (relative risk, 1.732; 95% CI, 1.300-2.309; P<.0001), PS (relative risk, 1.719; 95% CI, 1.269-2.327, P<.0001), LDH level (relative risk, 1.905; 95% CI, 1.415-2.564; P<.0001), and bone marrow involvement (relative risk, 1.454; 95% CI, 1.045-2.023; P=.026) were factors independently predictive for survival. Using these 4 variables we constructed a new prognostic model that singled out 4 groups at different risk: group 1, no adverse factors, with 5-year and 10-year OS of 62.3% and 54.9%, respectively; group 2, one factor, with a 5-year and 10-year OS of 52.9% and 38.8%, respectively; group 3, 2 factors, with 5-year and 10-year OS of 32.9% and 18.0%, respectively; group 4,3 or 4 factors, with a 5-year and 10-year OS of 18.3 and 12.6%, respectively (Pless than or equal to.0001; log-rank, 66.79)

Persistent Unresolved Inflammation in the Mecp2-308 Female Mutated Mouse Model of Rett Syndrome

Rett syndrome (RTT) is a rare neurodevelopmental disorder usually caused by mutations in the X-linked gene methyl-CpG-binding protein 2 (MECP2). Several Mecp2 mutant mouse lines have been developed recapitulating part of the clinical features. In particular, Mecp2-308 female heterozygous mice, bearing a truncating mutation, are a validated model of the disease. While recent data suggest a role for inflammation in RTT, little information on the inflammatory status in murine models of the disease is available. Here, we investigated the inflammatory status by proteomic 2-DE/MALDI-ToF/ToF analyses in symptomatic Mecp2-308 female mice. Ten differentially expressed proteins were evidenced in the Mecp2-308 mutated plasma proteome. In particular, 5 positive acute-phase response (APR) proteins increased (i.e., kininogen-1, alpha-fetoprotein, mannose-binding protein C, alpha-1-antitrypsin, and alpha-2-macroglobulin), and 3 negative APR reactants were decreased (i.e., serotransferrin, albumin, and apolipoprotein A1). CD5 antigen-like and vitamin D-binding protein, two proteins strictly related to inflammation, were also changed. These results indicate for the first time a persistent unresolved inflammation of unknown origin in the Mecp2-308 mouse model

COMPREHENSIVE ANALYSIS OF BASELINE OUTCOME BIOPREDICTORS IN YOUNGER PATIENTS WITH MANTLE CELL LYMPHOMA: THE ANCILLARY BIOLOGICAL STUDIES OF FONDAZIONE ITALIANA LINFOMI (FIL) MCL0208 CLINICAL TRIAL

Despite the improvement in therapeutic schedules, a relevant fraction of mantle cell lymphoma (MCL) patients still experience primary treatment failure. This is due to a deep biological heterogeneity, not adequately dissected by the clinical predictors alone, as the MIPI (MCL International Prognostic Index). The Fondazione Italiana Linfomi (FIL) MCL0208 trial (NCT02354313) is a prospective, randomized phase III trial comparing lenalidomide maintenance vs observation after an intensive citarabine containing chemo-immunotherapy followed by autologous transplantation in frontline MCL patients <66 years.[Ladetto, ASH 2018] Several biological ancillary studies were planned upfront, prospectively investigating the prognostic impact of putative biomarkers. Here we present a comprehensive analysis of the clinical impact of all the identified biopredictors

Induction chemotherapy stategies for primary mediastinal large B-cell lymphoma with sclerosis: a retrospective multinational study on 426 previously untreated patients.

BACKGROUND AND OBJECTIVES: This multinational retrospective study compares the outcomes of patients with primary mediastinal large B-cell lymphoma (PMLBCL) with sclerosis after first-generation (dose-intensive regimens), third-generation (alternating regimens) and high-dose chemotherapy strategies, frequently with adjuvant radiation therapy. DESIGN AND METHODS: Between August 1981 and December 1999, a total of 426 previously untreated patients with confirmed diagnosis were enrolled in 20 institutions to receive combination chemotherapy with either first generation (CHOP or CHOP-like) regimens, third generation (MACOP-B, VACOP-B, ProMACE CytaBOM) regimens or high-dose chemotherapy (HDS/ABMT). RESULTS: With chemotherapy, complete response (CR) rates were 49% (50/105), 51% (142/277) and 53% (23/44) with first generation, third generation and high-dose chemotherapy strategies, respectively; partial response (PR) rates were 32%, 36% and 35%, respectively. All patients who achieved CR and 124/142 (84%) with PR had radiation therapy on the mediastinum. The final CR rates became 61% for CHOP/CHOP-like regimens, 79% for MACOP-B and other regimens, and 75% for HDS/ABMT. After median follow-ups from attaining CR of 48.5 months for CHOP/CHOP-like regimens, 51.7 months for MACOP-B type regimens and 32.4 months for HDS/ABMT, relapses occurred in 15/64 (23%), 27/218 (12%) and 0/33 (0%) patients, respectively. Projected 10-year progression-free survival rates were 35%, 67% and 78%, respectively (p=0.0000). Projected 10-year overall survival rates were 44%, 71% and 77%, respectively (p=0.0000), after median follow-ups from diagnosis of 52.3 months, 54.9 months and 35.8 months, respectively. INTERPRETATION AND CONCLUSIONS: In patients with PMLBCL with sclerosis, MACOP-B plus radiation therapy may be a better strategy than other treatments; these retrospective data need to be confirmed by prospective studies. The encouraging survival results after high dose chemotherapy require confirmation in selected high-risk patients

Splenic marginal zone lymphoma: a prognostic model for clinical use.

The Integruppo Italiano Linfomi (IIL) carried out a study to assess the outcomes of splenic marginal zone lymphoma and to identify prognostic factors in 309 patients. The 5-year cause-specific survival (CSS) rate was 76%. In univariate analysis, the parameters predictive of shorter CSS were hemoglobin levels below 12 g/dL (P < .001), albumin levels below 3.5 g/dL (P = .001), International Prognostic Index (IPI) scores of 2 to 3 (P < .001), lactate dehydrogenase (LDH) levels above normal (P < .001), age older than 60 years (P = .01), platelet counts below 100 000/μL (P = .04), HbsAg-positivity (P = .01), and no splenectomy at diagnosis (P = .006). Values that maintained a negative influence on CSS in multivariate analysis were hemoglobin level less than 12 g/dL, LDH level greater than normal, and albumin level less than 3.5 g/dL. Using these 3 variables, we grouped patients into 3 prognostic categories: low-risk group (41%) with no adverse factors, intermediate-risk group (34%) with one adverse factor, and high-risk group (25%) with 2 or 3 adverse factors. The 5-year CSS rate was 88% for the low-risk group, 73% for the intermediate-risk group, and 50% for the high-risk group. The cause-specific mortality rate (x 1000 person-years) was 20 for the low-risk group, 47 for the intermediate-risk group, and 174 for the high-risk group. This latter group accounted for 54% of all lymphoma-related deaths. In conclusion, with the use of readily available factors, this prognostic index may be an effective tool for evaluating the need for treatment and the intensity of therapy in an individual patient. © 2006 by The American Society of Hematology

Role of blood cells dynamism on hemostatic complications in low-risk patients with essential thrombocythemia

Patients with essential thrombocythemia (ET) aged less than 60 years, who have not suffered a previous vascular event (low-risk patients), may develop thrombotic or hemorrhagic events. So far, it has not been possible to identify useful markers capable of predicting which of these patients are more likely to develop an event and therefore who needs to be treated. In the present study, we analysed the relationship between vascular complications and longitudinal blood counts of 136 low-risk ET patients taken over a sustained period of time (blood cells dynamism). After a median follow-up of 60 months, 45 out of 136 patients (33%) suffered 40 major thrombotic and 5 severe hemorrhagic complications. A total number of 5,781 blood counts were collected longitudinally. Thrombotic and hemorrhagic events were studied together (primary endpoint) but also separately (thrombotic alone = secondary endpoint; hemorrhagic alone = tertiary endpoint). The primary endpoint showed no significant association between platelet and WBC count at diagnosis and risk of any event (platelet, p = 0.797; WBC, p = 0.178), while Hb at baseline did show an association (p = 0.024). In the dynamic analysis with Cox regression model, where the blood count values were studied by time of follow-up, we observed that the risk for Hb was 1.49 (95% CI 1.13-1.97) for every increase of 1 g/dL, and that this risk then marginally decreased during follow-up. WBC was associated with an increased risk at baseline for every increase of 1 7 10(9)/L (hazard ratio (HR) 1.07, 95% CI 1.01-1.13, p = 0.034), the risk was stable during follow-up (HR 0.95, p = 0.187 at 60 months). Also, for each increment at baseline of 100 7 10(9) platelets/L, HR was increased by 1.08 (95% CI 0.97-1.22, p = 0.159) and decreases during follow-up. In conclusion, this study is the first to evaluate in ET low-risk patients, the risk of developing a thrombotic/hemorrhagic event considering blood counts over time. Overall our study shows that the risk changes over time. For example, the risk associated with WCC is not linear as previously reported. An interesting new finding is that PLT and even Hb contribute to the risk of developing vascular events. Future treatments should take into consideration these findings and aim to control all parameters over time. We believe this early study may help develop a dynamic analysis model to predict thrombosis in the single patient. Further studies are now warranted to further validate our findings