A B-cell receptor-related gene signature predicts survival in mantle cell lymphoma: Results from the Fondazione Italiana Linfomi MCL-0208 trial

Mantle cell lymphoma patients have variable clinical courses, ranging from indolent cases that do not require immediate treatment to aggressive, rapidly progressing diseases. Thus, diagnostic tools capable of stratifying patients according to their risk of relapse and death are needed. This study included 83 samples from the Fondazione Italiana Linfomi MCL-0208 clinical trial. Through gene expression profiling and quantitative real-time PCR we analyzed 46 peripheral blood and 43 formalin-fixed paraffin-embedded lymph node samples. A prediction model to classify patients was developed. By analyzing the transcriptome of 27 peripheral blood samples, two subgroups characterized by a differential expression of genes from the B-cell receptor pathway (B-cell receptor low and B-cell receptor high ) were identified. The prediction model based on the quantitative real-time PCR values of six representative genes (AKT3, BCL2, BTK, CD79B, PIK3CD, and SYK), was used to classify the 83 cases (43 B-cell receptor low and 40 B-cell receptor high ). The B-cell receptor high signature associated with shorter progression-free survival (P=0.0074), selected the mantle cell lymphoma subgroup with the shortest progression-free survival and overall survival (P=0.0014 and P=0.029, respectively) in combination with high ( extgreater30%) Ki-67 staining, and was an independent predictor of short progression-free survival along with the Mantle Cell Lymphoma International Prognostic Index-combined score. Moreover, the clinical impact of the 6-gene signature related to the B-cell receptor pathway identified a mantle cell lymphoma subset with shorter progression-free survival intervals also in an external independent mantle cell lymphoma cohort homoge-nously treated with different schedules. In conclusion, this 6-gene signature associates with a poor clinical response in the context of the MCL-0208 clinical trial. (clinicaltrials.gov identifier: 02354313)

The effect of slaughtering methods on actin degradation and on muscle quality attributes of farmed European sea bass (Dicentrarchus labrax).

In the current study, two different slaughtering procedures, spiking vs immersion in water/ice slurry, were applied on electrically stunned European sea bass (Dicentrarchus labrax) and the effects on actin degradation and fillet quality attributes were investigated. Rigor mortis index was similar for the two slaughtering techniques, whereas the shear force measurement indicated that rigor mortis occurred more quickly and intensely in the water/ice handled fish than in those slaughtered by spiking. The water/ice immersion procedure also resulted in higher amount of actin fragments than spiking. Muscle tissue apparent viscosity and water holding capacity were lower in sea bass treated in water/ice slurry compared with fish handled by spiking, whereas the acidification patterns of the two groups were not easily distinguishable. In conclusion, spiking appeared to preserve actin integrity better that water/ice and it seemed to ensure less muscle damage as indicated by the higher viscosity and water holding capacity values. Finally, a role of actin as a biochemical marker for the prediction of fish quality was suggested

Neuroinvasive West Nile Infection with an Unusual Clinical Presentation: A Single-Center Case Series

The 2018 West Nile Virus (WNV) season in Europe was characterized by an extremely high infection rate and an exceptionally higher burden when compared to previous seasons. Overall, there was a 10.9-fold increase in incidence in Italy, with 577 human cases, 230 WNV neuroinvasive diseases (WNNV) and 42 WNV-attributed deaths. Methods: in this paper we retrospectively reported the neurological presentation of 7 patients admitted to University Hospital of Udine with a diagnosis of WNNV, especially focusing on two patients who presented with atypical severe brain stem involvement. Conclusions: the atypical features of some of these forms highlight the necessity to stay vigilant and suspect the diagnosis when confronted with neurological symptoms. We strongly encourage clinicians to consider WNNV in patients presenting with unexplained neurological symptoms in mild climate-areas at risk

The effect of the pre-slaughter feeding/fasting schedule on post mortem quality traits of rainbow trout

Few studies have investigated the influence of pre-slaughter feeding-fasting history of cultured fish on quality traits of raw fillets. Short pre-slaughter fasting periods (3-9 days) led to slight changes in Salmonid fillet quality, whereas longer starvation (35 days) resulted in improved pre-slaughter resistance to stress and delayed rigor (L\uf2pez-Luna et al., 2014; Bermejo-Poza et al., 2015; M\uf8rk\uf8re et al., 2008). The aim of this study was to evaluate the effect of a 3-week pre-slaughter fasting or feed restriction period on the evolution of post mortem quality traits of fillet of large rainbow trout (O. mykiss). Fish groups, each consisting of 40 specimens (695g) kept at 13.2\ub10.1\ub0C in 2.5 m3 circular tanks, were fed a full ration (FR, 0.66% biomass day-1) or a restricted one (RR, 30% of FR) or were kept starved (R0) over three weeks before slaughtering. Fish were rapidly sacrificed by percussion and five fish per treatment were stored on ice for recording evolution of rigor mortis. Other fish were subjected to biometry and dressing out yield measurements. Fillets were analyzed for proximate analysis and physicochemical traits over 72 h of cold storage (+4\ub0C). Dorsal muscle samples were quickly excised and stored in liquid nitrogen until actin degradation analysis. At slaughter, fish previously fed a full ration gained some weight (+14%) while a weight loss occurred in starved fish (-4.4%) and in those given a restricted ration (-1.6%). Fillet proximate composition was not affected (P>0.05) by the pre-slaughter treatment. A pre-slaughter restricted ration induced higher variability in fish size and certain quality traits such as WHC and texture. It also resulted in faster muscle actin degradation during the first post mortem hours (P<0.05). Despite the weight loss and decreased muscle redness (P<0.05), pre-slaughter starved fish had higher slaughter yield, better muscle firmness after 24 h in cold, extended pre-rigor phase, higher pH and improved WHC values after 7 h, than both full or restricted fed fish (P<0.05). The present study suggest that an extended pre slaughter fasting period could result in improved technological quality traits in rainbow trout

Towards measles elimination in Italy: Virological surveillance and genotypes trend (2013-2015).

In accordance with the goal of the World Health Organization Regional Office for Europe, the Italian National Measles and Rubella Elimination Plan aimed to interrupt indigenous measles transmission in Italy by the end of 2015. However, from 2013 to 2015, Italy experienced high measles burden with 4902 measles cases (49.3% laboratory-confirmed) reported to the enhanced measles surveillance system (cumulative incidence in the triennium reference period: 2.4/100,000 population). The measles elimination goal was not reached. Laboratory surveillance of measles circulating genotypes is performed by the Measles and Rubella National Reference Laboratory (NRL) at the Italian National Institute of Health (Istituto Superiore di Sanit\ue0 - ISS), in Rome. Samples received from 1 January 2013-31 December 2015 were analysed. Those positive for measles genome by molecular tests were sequenced and phylogenetically analysed. Phylogenetic analysis performed by NRL identified that genotypes D4 and D8 were endemic and co-circulated in 2011-2013: study results show that genotype D4 disappeared during 2013. Sporadic cases were associated to genotype B3 during 2011-2013, which became endemic in Italy during 2014 and co-circulated with D8 until 2015. Sporadic cases were found belonging to genotypes D9 and H1 all over the period in exam. Similar trend has been observed in European WHO Region

TP53 mutations with low variant allele frequency predict short survival in chronic lymphocytic leukemia

Purpose: In chronic lymphocytic leukemia (CLL), TP53 mutations are associated with reduced survival and resistance to standard chemoimmunotherapy (CIT). Nevertheless, the clinical impact of subclonal TP53 mutations below 10% to 15% variant allele frequency (VAF) remains unclear. Experimental Design: Using a training/validation approach, we retrospectively analyzed the clinical and biological features of TP53 mutations above (high-VAF) or below (low-VAF) the previously reported 10.0% VAF threshold, as determined by deep next-generation sequencing. Clinical impact of low-VAF TP53 mutations was also confirmed in a cohort (n = 251) of CLL treated with fludarabine-cyclophosphamide-rituximab (FCR) or FCR-like regimens from two UK trials. Results: In the training cohort, 97 of 684 patients bore 152 TP53 mutations, while in the validation cohort, 71 of 536 patients had 109 TP53 mutations. In both cohorts, patients with the TP53 mutation experienced significantly shorter overall survival (OS) than TP53 wild-type patients, regardless of the TP53 mutation VAF. By combining TP53 mutation and 17p13.1 deletion (del17p) data in the total cohort (n = 1,220), 113 cases were TP53 mutated only (73/113 with low-VAF mutations), 55 del17p/TP53 mutated (3/55 with low-VAF mutations), 20 del17p only, and 1,032 (84.6%) TP53 wild-type. A model including low-VAF cases outperformed the canonical model, which considered only high-VAF cases (c-indices 0.643 vs. 0.603, P < 0.0001), and improved the prognostic risk stratification of CLL International Prognostic Index. Clinical results were confirmed in CIT-treated cases (n = 552) from the retrospective cohort, and the UK trials cohort. Conclusions: TP53 mutations affected OS regardless of VAF. This finding can be used to update the definition of TP53 mutated CLL for clinical purposes

Measles in Italy: Viral strains and crossing borders

In 2017, Italy experienced one of the largest outbreaks of measles in recent years, with 5404 notified cases and 4347 confirmed cases. A further 2029 cases were notified during the first 6 months of 2018, and 1516 of them were laboratory-confirmed. The B3 and D8 genotypes were identified as those responsible for the outbreak. Possible transmission routes can be established by monitoring the circulating measles virus strains in support of the national health authorities to warn people and travellers

A 6-GENE EXPRESSION SIGNATURE IN MANTLE CELL LYMPHOMA: RESULTS FROM THE FONDAZIONE ITALIANA LINFOMI (FIL)-MCL-0208 TRIAL

Background: The aggressive clinical behavior of mantle cell lymphoma (MCL) is mainly attributed to the t(11;14)(q13;q32) traslocation and cyclin D1 (CCND1) overexpression. Nevertheless, a certain degree of clinical/biological heterogeneity has been reported. Aims: To identify MCL subsets with peculiar clinical/biological features in the context of a cohort of homogeneously treated MCL patients. Methods: The study used gene expression profiling (GEP) and quantitative real-time PCR (qRT-PCR) validations in peripheral blood (PB, n=46) and formalin fixed paraffin embedded (FFPE, n=42) samples from 82 MCL cases enrolled in the Fondazione Italiana Linfomi (FIL)-MCL-0208 randomized clinical trial (high-dose therapy followed by autologous transplantation). Results: i) Unsupervised and supervised analyses. GEP from 27 PB samples were analyzed by principal component analysis (PCA) and divided in two subgroups named PCA1 (14 cases) and PCA2 (13 cases). Supervised analysis, according to PCA classification, identified a gene expression signature of 902 probes (700 up-regulated). Gene Set Enrichment Analysis (GSEA) demonstrated a significant enrichment of five B Cell Receptor (BCR)-related gene sets, these genes being constitutively over-expressed in PCA2 samples. ii) Identification of a \u201cPCA2-type\u201d gene signature. By merging the lists of differentially expressed genes and the BCR signaling related genes according to GSEA, a group of 14 genes, all overexpressed in PCA2 cases, was obtained. Among these genes, 6 genes, AKT3, BCL2, BTK, CD79B, PIK3CD, and SYK, were selected for further validations. iii) Generation of a 6-gene prediction model. These 6 genes were analyzed by qRT-PCR and utilized to generate a prediction model by using 17 cases as training cohort and 10 cases as validation cohort (all from PB samples). By this approach, 10/10 cases of the validation cohort were correctly assigned according to the PCA2/PCA1 classification. qRT-PCR was then utilized to classify 19 additional cases (10 PCA2 cases) not employed in GEP. Overall, in the 46 cases, 23 cases were classified as PCA2 by the GEP/qRT-PCR approach. iv) Clinical/biological correlations. N