Gene expression profiling and FDG-PET radiomics uncover radiometabolic signatures associated with outcome in DLBCL.

Emerging evidence indicates that chemoresistance is closely related to altered metabolism in cancer. Here, we hypothesized that distinct metabolic gene expression profiling (GEP) signatures might be correlated with outcome and with specific fluorodeoxyglucose positron emission tomography (FDG-PET) radiomic profiles in diffuse large B-cell lymphoma (DLBCL). We retrospectively analyzed a discovery cohort of 48 consecutive patients with DLBCL treated at our center with standard first-line chemoimmunotherapy by performing targeted GEP (T-GEP)- and FDG-PET radiomic analyses on the same target lesions at baseline. T-GEP-based metabolic profiling identified a 6-gene signature independently associated with outcomes in univariate and multivariate analyses. This signature included genes regulating mitochondrial oxidative metabolism (SCL25A1, PDK4, PDPR) that were upregulated and was inversely associated with genes involved in hypoxia and glycolysis (MAP2K1, HIF1A, GBE1) that were downregulated. These data were validated in 2 large publicly available cohorts. By integrating FDG-PET radiomics and T-GEP, we identified a radiometabolic signature (RadSig) including 4 radiomic features (histo kurtosis, histo energy, shape sphericity, and neighboring gray level dependence matrix contrast), significantly associated with the metabolic GEP-based signature (r = 0.43, P = .0027) and with progression-free survival (P = .028). These results were confirmed using different target lesions, an alternative segmentation method, and were validated in an independent cohort of 64 patients. RadSig retained independent prognostic value in relation to the International Prognostic Index score and metabolic tumor volume (MTV). Integration of RadSig and MTV further refined prognostic stratification. This study provides the proof of principle for the use of FDG-PET radiomics as a tool for noninvasive assessment of cancer metabolism and prognostic stratification in DLBCL.

[Euthanasia and Assisted Suicide: nursing perceptions survey]. / Eutanasia e Suicidio assistito: indagine sulla percezione del personale infermieristico.

INTRODUCTION: Despite the possibility of providing palliative care, the global requests of patients to be included in assisted suicide and euthanasia pathways have significantly increased in the last 15 years. According to the law, the discussion on these procedures is still open in many countries, including Italy. Therefore, it is important to investigate the opinion of health care workers. METHODS: A questionnaire was designed and administered to nurses working in two hospitals in Milan, with the aim of investigating their opinion and working propensity in the context of assisted suicide. The instrument has undergone a preliminary validation process to in order to asses its psychometric properties. RESULTS: The opinions of the sample (n=430) were mostly in favor of assisted suicide and euthanasia; however, as regards "propensity", only a small majority was in favor or very much in favor of working in contexts where the procedures described above were practiced, with increase in undecided and in those against. DISCUSSION: According to the Italian law in force, anyone participating in assisted suicide or euthanasia procedures would be prosecuted by law; this implies that healthcare professionals do not have direct knowledge of assisted dying procedures and could be an explanation for the large numbers of undecided respondents in the last questions of the questionnaire. In spite of the limitations of the survey carried out, consisting mainly in the limited sample and in the monocentric design, the opinion of the staff seems to be largely in favor of the patient's freedom of choice; it is likely that similar percentages are justified by a deep-rooted direct experience in a general situation where the assistance that can be provided to the patient is not sufficient.

Shaping pseudoneglect with transcranial cerebellar direct current stimulation and music listening.

Non-invasive brain stimulation modulates cortical excitability depending on the initial activation state of the structure being stimulated. Combination of cognitive with neurophysiological stimulations has been successfully employed to modulate responses of specific brain regions. The present research combined a neurophysiological pre-conditioning with a cognitive conditioning stimulation to modulate behavior. We applied this new state-dependency approach to investigate the cerebellar role in musical and spatial information processing, given that a link between musical perception and visuo-spatial abilities and a clear cerebellar involvement in music perception and visuo-spatial tasks have been reported. Cathodal, anodal or sham transcranial cerebellar Direct Current Stimulation (tcDCS) pre-conditioning was applied on the left cerebellar hemisphere followed by conditioning stimulation through music or white noise listening in a sample of healthy subjects performing a Line Bisection Task (LBT). The combination of the cathodal stimulation with music listening resulted in a marked attentional shift toward the right hemispace, compensating thus the natural leftward bias of the baseline condition (pseudoneglect). Conversely, the anodal or sham pre-conditioning stimulations combined with either music and white noise conditioning listening did not modulate spatial attention. The efficacy of the combined stimulation (cathodal pre-conditioning and music conditioning) and the absence of any effect of the single stimulations provide a strong support to the state-dependency theory. They propose that tcDCS in combination with music listening could act as a rehabilitative tool to improve cognitive functions in the presence of neglect or other spatial disorders.