Assessment of efficacy of dendritic cell therapy and viral therapy in high grade glioma clinical trials. A meta-analytic review

ABSTRACT

In recent years, immunotherapy has raised the interest of many studies and provided different perspectives for the therapeutic management of high grade glioma. Our meta-analysis focused on the effectiveness of dendritic cell (DC) therapy and viral therapy (VT) in clinical trials. Fourteen eligible studies have been evaluated and the results suggest the improvement of both OS (HR = 0.65) (p < 0.0001) and PFS (HR = 0.59) (p = 0.01) for patients receiving DC therapy. The data for VT showed a slight improvement in terms of OS (HR = 0.81), while PFS was similar to the control arms (HR = 1.06) (p = 0.41).     

Peripheral Immunotype Correlates with Minimal Residual Disease Status and Is Modulated by Immunomodulatory Drugs in Multiple Myeloma

Data indicate reversal of immune dysfunction with active treatment; however, the precise contribution of specific immune effector and immune suppressor components to achieve a minimal residual disease (MRD) state and immunomodulatory drug–mediated immunomodulatory effects in multiple myeloma (MM) patients remains poorly understood. In this prospective proof-of-principle study we sought to determine the dynamic alterations in natural killer (NK), NK-T, and T cells, including maturation and activating/inhibitory repertoire associated with MRD^pos versus MRD^neg status after autologous stem cell transplantation (ASCT) and during lenalidomide-based maintenance therapy. Of the 46MM patients enrolled, 36 had bone marrow MRD assessment 60+ days post-ASCT, 30 had longitudinal blood immunotyping during maintenance (pretherapy and after cycles 1, 3, and 6), and 20 had both MRD assessment and longitudinal immunotyping. Multicolor flow cytometry was used for MRD and immunotyping. Although the absolute number of NK cells was significantly lower in patients with MRD^pos response, phenotypically NK cells in these patients displayed higher expression of activating receptors KIRDS4 and decreased expression of inhibitory molecules NKG2A compared with the MRD^neg group. Furthermore, we observed significantly lower frequencies of T cells displaying KIR3DL1 in MRD^pos versus MRD^neg patients. Longitudinal immunotyping during lenalidomide maintenance showed loss of mature NK effector function, augmentation of NK-T effector function, and acquisition of PD1 independent anergic state. Our findings also suggest skewing of T cells toward an exhausted state during the maintenance phase in MRD^pos patients. Put together, these observations provide a distinctive signature for MRD^neg and MRD^pos groups. These data support exploration of immune profiling in prospective clinical trials according to MRD-defined responses to identify patients that may benefit from maintenance intensification/modification or maintenance withdrawal.     

An In-Situ Electrochemical Nanoindentation (ECNI) Study on the Effect of Hydrogen on the Mechanical Properties of 316L Austenitic Stainless Steel

In-situ electrochemical nanoindentation (ECNI) has been used to study the effect of hydrogen on the mechanical properties of austenitic stainless steel AISI 316L. Changing the electrode potential (via electrochemical charging) revealed the interconnected nature of the hydrogen effect on the nanomechanical properties of the stainless steel. At more positive cathodic potentials, a softening effect of hydrogen can be noticed, while significant hardening can be observed at more negative cathodic potentials. The hydrogen effects on the nanomechanical properties were analyzed in terms of the homogeneous dislocation nucleation (HDN) and the hydrogen-dislocation interactions from the energy point of view. The effects can be explained with the framework of the defactant theory and the hydrogen-enhanced localized plasticity (HELP) mechanism.     

Experimental Study on the Corrosion of Carbon Steel and Aluminum Alloy in Firefighting Protein Foam Concentrates

The corrosion of mild steel and Al alloy in Fomtec P 6% and 6% P Profoam 806 protein-based foam concentrates was investigated. Weight-loss data for steel showed corrosion penetration of 0.745 mipy in Fomtec and 2.269 mipy in Profoam, whereas for Al alloy the penetration levels were 0.474 and 1.093 mipy, respectively. Scanning electron microscopy and energy dispersive X-ray spectroscopy allowed characterization of the metallic surface covered or free from corrosion products. Values of corrosion potential, corrosion current density and corrosion penetration were calculated by using potentiodynamic polarization curves. Electrochemical impedance spectra illustrated the change in polarization resistance during anodic polarization. Data obtained by accelerated electrochemical methods confirm the greater aggressiveness of the Profoam concentrate compared to Fomtec concentrate.     

Self-reported mental health in children ages 6–12 years across eight European countries

Worldwide, approximately one in eight children or adolescents suffers from a mental disorder. The present study was designed to determine the self-reported prevalence of mental health problems in children aged 6–11 years across eight European countries including Italy, France, Germany, the Netherlands, Lithuania, Bulgaria, Romania, and Turkey. Data were drawn from 6245 children participating in the School Children Mental Health in Europe (SCHME) study and a large cross-sectional survey in France. Self-reported child mental health was assessed using the Dominique Interactive (DI). Overall, 22.0% of children were identified per their own evaluation as having at least one mental disorder, ranging from 16.4% in the Netherlands to 27.9% in Bulgaria. The prevalence of internalizing disorders was 18.4% across countries and ranged from 11.8% in the Netherlands to 24.3% in Turkey. The prevalence of externalizing disorders was lower with an average of 7.8%, ranging from 3.5% in Turkey to 10.5% in Bulgaria. Combining samples across European countries, 1 in 5 children reported internalizing problems and 1 in 12 children externalizing problems. The net completion rates of 4.1–74.3% preclude conclusions about national differences in prevalence rates.     

Hipertensão Arterial e Ácido Úrico Sérico em Idosos - Estudo SEPHAR III

Background:Hyperuricemia is a frequent finding in patients with arterial hypertension, and there is increasing evidence that this entity is also a risk factor for cardiovascular disease.Objective:In the context of an aging population, this study aims to evaluate serum uric acid levels and arterial hypertension prevalence and control in a subgroup of Romanian adults (>65 years), concerning the influence of age on these parameters.Method:The study sample consists of 1,920 adults included in SEPHAR III survey, of whom 447 were elderly patients (>65 years of age). During the two study visits, three blood pressure (BP) measurements were performed at 1-min intervals and serum uric acid levels, kidney function by estimated glomerular filtration rate, blood pressure, and intima media thickness measurements were conducted. Hypertension and controls were defined according to the current guidelines. Intima-media thickness evaluation was assessed by B-mode Doppler ultrasound evaluation. A significance level p < 0.05 was adopted for the statistical analysis.Results:Adult patients had a significant lower serum uric acid levels, compared to elderly patients, regardless of glomerular filtration rate levels. Adult patients showed a significantly lower intima-media thickness levels, when compared to elderly patients.Conclusion:Similar to previous studies, in the present study, age represented one of the factors contributing to the increased level of serum uric acid. An increasing prevalence of arterial hypertension with age, together with a poor control of blood pressure, was also obtained.