CAR-T CELL THERAPY FOR FOLLICULAR LYMPHOMAS

Follicular lymphoma is the second most diagnosed lymphoma in Western Europe. Significant advancements have considerably improved the survival of FL patients. However, 10-20% of these patients are refractory to standard treatments, and most of them will relapse. The treatment of follicular lymphoma patients with multiply relapsed or refractory disease represents an area of high-unmet needing new treatments with stronger efficacy. Chimeric antigen receptor (CAR)-T cell therapy targeting B-cell antigens, such as CD19 or CD20, is emerging as an efficacious treatment for R/R follicular lymphoma patients, particularly for those with early relapse and refractory to alkylating agents and to anti-CD20 monoclonal antibodies, resulting in a high rate of durable responses in a high proportion of patients.

Effects of 5-year experimental warming in the Alpine belt on soil Archaea: Multi-omics approaches and prospects

We currently lack a predictive understanding of how soil archaeal communities may respond to climate change, particularly in Alpine areas where warming is far exceeding the global average. Here, we characterized the abundance, structure, and function of total (by metagenomics) and active soil archaea (by metatranscriptomics) after 5-year experimental field warming (+1 C) in Italian Alpine grasslands and snowbeds. Our multi-omics approach unveiled an increasing abundance of Archaea during warming in snowbeds, which was negatively correlated with the abundance of fungi (by qPCR) and micronutrients (Ca and Mg), but positively correlated with soil water content. In the snowbeds transcripts, warming resulted in the enrichment of abundances of transcription and nucleotide biosynthesis. Our study provides novel insights into possible changes in soil Archaea composition and function in the climate change scenario

Small area estimation for unemployment using latent Markov models

In Italy, the Labor Force Survey (LFS) is conducted quarterly by the National Statistical Institute (ISTAT) to produce estimates of the labor force status of the population at different geographical levels. In particular, ISTAT provides LFS estimates of employed and unemployed counts for local Labor Market Areas (LMAs). LMAs are 611 sub-regional clusters of municipalities and are unplanned domains for which direct estimates have overly large sampling errors. This implies the need of Small Area Estimation (SAE) methods. In this paper we develop a new area level SAE method that uses a Latent Markov Model (LMM) as linking model. In LMMs, the characteristic of interest, and its evolution in time, is represented by a latent process that follows a Markov chain, usually of first order. Therefore, areas are allowed to change their latent state across time. The proposed model is applied to quarterly data from the LFS for the period 2004 to 2014 and fitted within a hierarchical Bayesian framework using a data augmentation Gibbs sampler. Estimates are compared with those obtained by the classical Fay-Herriot model, by a time-series area level SAE model, and on the basis of data coming from the 2011 Population Census

Cancer incidence in men: a cluster analysis of spatial patterns

Abstract Background Spatial clustering of different diseases has received much less attention than single disease mapping. Besides chance or artifact, clustering of different cancers in a given area may depend on exposure to a shared risk factor or to multiple correlated factors (e.g. cigarette smoking and obesity in a deprived area). Models developed so far to investigate co-occurrence of diseases are not well-suited for analyzing many cancers simultaneously. In this paper we propose a simple two-step exploratory method for screening clusters of different cancers in a population. Methods Cancer incidence data were derived from the regional cancer registry of Umbria, Italy. A cluster analysis was performed on smoothed and non-smoothed standardized incidence ratios (SIRs) of the 13 most frequent cancers in males. The Besag, York and Mollie model (BYM) and Poisson kriging were used to produce smoothed SIRs. Results Cluster analysis on non-smoothed SIRs was poorly informative in terms of clustering of different cancers, as only larynx and oral cavity were grouped, and of characteristic patterns of cancer incidence in specific geographical areas. On the other hand BYM and Poisson kriging gave similar results, showing cancers of the oral cavity, larynx, esophagus, stomach and liver formed a main cluster. Lung and urinary bladder cancers clustered together but not with the cancers mentioned above. Both methods, particularly the BYM model, identified distinct geographic clusters of adjacent areas. Conclusion As in single disease mapping, non-smoothed SIRs do not provide reliable estimates of cancer risks because of small area variability. The BYM model produces smooth risk surfaces which, when entered into a cluster analysis, identify well-defined geographical clusters of adjacent areas. It probably enhances or amplifies the signal arising from exposure of more areas (statistical units) to shared risk factors that are associated with different cancers. In Umbria the main clusters were characterized by high risks for cancers with alcohol and tobacco both as risk factors. Tobacco-only related cancers formed a separate cluster to the alcohol- and tobacco-related sites. Joint spatial analysis or investigation of hypothesized exposures might be used for further investigation into interesting geographical clusters.</p

Procalcitonin predicts real-time PCR results in blood samples from patients with suspected sepsis.

Early diagnosis and rapid bacterial identification are of primary importance for outcome of septic patients. SeptiFast® (SF) real-time PCR assay is of potential utility in the etiological diagnosis of sepsis, but it cannot replace blood culture (BC) for routine use in clinical laboratory. Procalcitonin (PCT) is a marker of sepsis and can predict bacteremia in septic patients. The aim of the present study was to investigate whether PCT serum levels could predict SF results, and could help screening febrile patients in which a SF assay can improve the etiological diagnosis of sepsis.From 1009 febrile patients with suspected sepsis, 1009 samples for BC, SF real-time PCR, and PCT determination were obtained simultaneously, and results were compared and statistically analysed. Receiver operating characteristic (ROC) curves were generated to determine the area under the curve and to identify which cut-off of PCT value produced the best sensitivity to detect SF results.Mean PCT values of sera drawn simultaneously with samples SF positive (35.42 ± 61.03 ng/ml) or BC positive (23.14 ± 51.56 ng/ml) for a pathogen were statistically higher than those drawn simultaneously with SF negative (0.84 ± 1.67 ng/ml) or BC negative (2.79 ± 16.64 ng/ml) samples (p<0.0001). For SF, ROC analysis showed an area under the curve of 0.927 (95% confidence interval: 0.899-0.955, p<0.0001). The PCT cut-off value of 0.37 ng/ml showed a negative predictive value of 99%, reducing the number of SF assays of 53.9%, still identifying the 96.4% of the pathogens.PCT can be used in febrile patients with suspected sepsis to predict SF positive or negative results. A cut-off value of 0.37 ng/ml can be considered for optimal sensitivity, so that, in the routine laboratory activity, SF assay should not be used for diagnosis of sepsis in an unselected patient population with a PCT value <0.37 ng/ml

Epigenetic changes in therapy-related MDS/AML

The purpose of this review is to update knowledge on therapy-related myeloid neoplasms (t-MNs), taken into account the new 2008 WHO classification, new genome-wide approaches for the definition of susceptibility towards t-MN and the introduction of new more aggressive treatments in cancer patients. Recent findings t-MNs are an increasing matter in cancer survivors treated with chemoradiotherapy. One of the major concerns in hematologic malignancies is childhood acute lymphoblastic leukemia (ALL), in which the leukemogenic role of extended etoposide/teniposide treatment, concomitant intensive antimetabolite and asparaginase, granulocyte colonystimulating factor (G-CSF) and prophylactic cranial radiotherapy use have been established. In high-risk Hodgkin lymphoma, 3% t-MNs have been observed at 10-year follow-up with the escalated BEACOPP schedule, versus 0.4% with ABVD. In lymphoproliferative diseases the new drugs fludarabine and lenalidomide may increase the risk of second tumors, when associated to other cytotoxic therapies. Among solid tumors, breast cancer is most frequently associated to t-MN. The risk is correlated to higher chemotherapy doses, radiotherapy, use of G-CSF, but also independent from treatment, suggesting a genetic predisposition to both diseases. Radiotherapy plays a role also in female pelvic tumors and in testicular cancer, when associated to cisplatin. Summary The risk of t-MN is not negligible, although below 2% in most series. This is particularly significant for younger cancer patients and during the first 5 years after the primary malignancies. Efforts should be maximized to identify susceptibility factors to identify patients at risk, in whom more leukemogenic drugs and schedules should be avoided

One hundred forty pathogens detected by SeptiFast (SF) and/or blood culture (BC) in 1009 patients.

1<p><i>Streptococcus</i> spp. group includes <i>S. agalactiae, S. pyogenes, S. anginosus</i>, <i>S. bovis</i>, <i>S. constellatus</i>, <i>S. cristatus</i>, <i>S. gordonii</i>, <i>S. intermedius, S. milleri, S. mitis, S. mutans, S. oralis, S. parasanguinis, S. salivarius, S. sanguinis, S. thermophilus, S. vestibularis, S. viridans</i>.</p>2<p>Coagulase-negative staphylococci group includes <i>S. epidermidis, S. haemolyticus, S. hominis, S. pasteuri, S. warneri, S. cohnii, S. lugdunensis, S. capitis, S. caprae, S. saprophyticus</i>, and <i>S. xylosus</i>.</p>3<p>ND, not included in the SF master list <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053279#pone.0053279-Lehmann1" target="_blank">[6]</a>.</p

Surfactant replacement therapy in combination with different non-invasive ventilation techniques in spontaneously-breathing, surfactant-depleted adult rabbits.

Nasal intermittent positive pressure ventilation (NIPPV) holds great potential as a primary ventilation support method for Respiratory Distress Syndrome (RDS). The use of NIPPV may also be of great value combined with minimally invasive surfactant delivery. Our aim was to implement an in vivo model of RDS, which can be managed with different non-invasive ventilation (NIV) strategies, including non-synchronized NIPPV, synchronized NIPPV (SNIPPV), and nasal continuous positive airway pressure (NCPAP). Forty-two surfactant-depleted adult rabbits were allocated in six different groups: three groups of animals were treated with only NIV for three hours (NIPPV, SNIPPV, and NCPAP groups), while three other groups were treated with surfactant (SF) followed by NIV (NIPPV+SF, SNIPPV+SF, and NCPAP+SF groups). Arterial gas exchange, ventilation indices, and dynamic compliance were assessed. Post-mortem the lungs were sampled for histological evaluation. Surfactant depletion was successfully achieved by repeated broncho-alveolar lavages (BALs). After BALs, all animals developed a moderate respiratory distress, which could not be reverted by merely applying NIV. Conversely, surfactant administration followed by NIV induced a rapid improvement of arterial oxygenation in all surfactant-treated groups. Breath synchronization was associated with a significantly better response in terms of gas exchange and dynamic compliance compared to non-synchronized NIPPV, showing also the lowest injury scores after histological assessment. The proposed in vivo model of surfactant deficiency was successfully managed with NCPAP, NIPPV, or SNIPPV; this model resembles a moderate respiratory distress and it is suitable for the preclinical testing of less invasive surfactant administration techniques

Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio of different cut-off values of PCT on SeptiFast results.

<p>PPV = positive predictive value.</p><p>NPV = negative predictive value.</p><p>LR+ = positive likelihood ratio.</p><p>LR− = negative likelihood ratio.</p