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Background Tumor PD-L1 expression is a predictive biomarker for patients with NSCLC receiving PD-(L)1 blockade agents. However, although increased tumor PD-L1 expression predicts responsiveness, clinical benefit has been observed regardless of tumor PD-L1 expression, suggesting the existence of other PD-L1 sources. The aim of our study was to analyze whether integrating systemic and tumor PD-L1 is more predictive of efficacy in patients with advanced NSCLC receiving PD-(L)1 blockade agents. Material and methods Twenty-nine healthy donors and 119 consecutive patients with advanced NSCLC treated with PD-(L)1 drug were prospectively included. Pretreatment blood samples were collected to evaluate PD-L1 levels on circulating immune cells, platelets (PLTs), platelet microparticles (PMPs), and the plasma soluble PD-L1 concentration (sPD-L1). Tumor PD-L1 status was assessed by immunohistochemistry. The percentages of circulating PD-L1 + leukocytes, sPD-L1 levels, and tumor PD-L1 were correlated with efficacy. Results No differences in the percentages of circulating PD-L1 + leukocytes were observed according to tumor PD-L1 expression. Significantly longer progression-free survival was observed in patients with higher percentages of PD-L1 + CD14 + , PD-L1 + neutrophils, PD-L1 + PLTs, and PD-L1 + PMPs and significantly longer overall survival was observed in patients with higher percentages of PD-L1 + CD14 + and high tumor PD-L1 expression. Integrating the PD-L1 data of circulating and tumor PD-L1 results significantly stratified patients according to the efficacy of PD-(L1) blockade agents. Conclusions Our results suggest that integrating circulating PD-L1 + leukocytes, PLT, PMPs, and sPD-L1 and tumor PD-L1 expression may be helpful to decide on the best treatment strategy in patients with advanced NSCLC who are candidates for PD-(L)1 blockade agents.

The aim was to develop a predictive model of infection by multidrug-resistant microorganisms (MDRO). A national, retrospective cohort study was carried out including all patients attended for an infectious disease in 54 Spanish Emergency Departments (ED), in whom a microbiological isolation was available from a culture obtained during their attention in the ED. A MDRO infection prediction model was created in a derivation cohort using backward logistic regression. Those variables significant at p < 0.05 assigned an integer score proportional to the regression coefficient. The model was then internally validated by k-fold cross-validation and in the validation cohort. A total of 5460 patients were included; 1345 (24.6%) were considered to have a MDRO infection. Twelve independent risk factors were identified in the derivation cohort and were combined into an overall score, the ATM (assessment of threat for MDRO) score. The model achieved an area under the curve-receiver operating curve of 0.76 (CI 95% 0.74-0.78) in the derivation cohort and 0.72 (CI 95% 0.70-0.75) in the validation cohort (p = 0.0584). Patients were then split into 6 risk categories and had the following rates of risk: 7% (0-2 points), 16% (3-5 points), 24% (6-9 points), 33% (10-14 points), 47% (15-21 points), and 71% (> 21 points). Findings were similar in the validation cohort. Several patient-specific factors were independently associated with MDRO infection risk. When integrated into a clinical prediction rule, higher risk scores and risk classes were related to an increased risk for MDRO infection. This clinical prediction rule could be used by providers to identify patients at high risk and help to guide antibiotic strategy decisions, while accounting for clinical judgment.

Chemokines are small, secreted molecules that mediate inflammatory reactions. Neurons and astrocytes constitutively express chemokines implicated in the process of neuroinflammation associated with neurodegenerative diseases. The monocyte chemoattractant protein-1 (MCP-1) has been widely related to this process. However, the constitutive expression of this molecule by neurons has not been elucidated so far. In this study, we set out to characterize the neurochemical phenotype of MCP-1-expressing neurons in the rat neocortex to infer its role in basal conditions. We observed the presence of two populations of neurons expressing MCP-1: One population of cells with weak expression of MCP-1 corresponding to principal neurons (Tbr-1 positive) and a second population with high expression of MCP-1 corresponding to inhibitory neurons (GAD-67 positive), in particular to CCK/CBR1 interneurons. Moreover, high MCP-1-expressing neurons were metabolically active (pCREB positive). The population of CCK interneurons that co-localizes with MCP-1 corresponds to the regular-spiking basket cells and is co-responsible for the perisomatic inhibition of principal pyramidal neurons. Previous studies have demonstrated that MCP-1 can alter the electric properties of neurons and a tonic function for this molecule has been postulated. As CCK-inhibitory neurons are affected in mood disorders, whether the expression of MCP-1 was maintained in humans could be part of the link between inflammatory responses and observed changes in mood state. Copyright © 2020 Elsevier B.V. All rights reserved.

Allogeneic cardiac stem cells (AlloCSC-01) have shown protective, immunoregulatory, and regenerative properties with a robust safety profile in large animal models of heart disease.To investigate the safety and feasibility of early administration of AlloCSC-01 in patients with ST-segment-elevation myocardial infarction.CAREMI (Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With STEMI and Left Ventricular Dysfunction) was a phase I/II multicenter, randomized, double-blind, placebo-controlled trial in patients with ST-segment-elevation myocardial infarction, left ventricular ejection fraction ≤45%, and infarct size ≥25% of left ventricular mass by cardiac magnetic resonance, who were randomized (2:1) to receive AlloCSC-01 or placebo through the intracoronary route at days 5 to 7. The primary end point was safety and included all-cause death and major adverse cardiac events at 30 days (all-cause death, reinfarction, hospitalization because of heart failure, sustained ventricular tachycardia, ventricular fibrillation, and stroke). Secondary safety end points included major adverse cardiac events at 6 and 12 months, adverse events, and immunologic surveillance. Secondary exploratory efficacy end points were changes in infarct size (percentage of left ventricular mass) and indices of ventricular remodeling by magnetic resonance at 12 months. Forty-nine patients were included (92% male, 55±11 years), 33 randomized to AlloCSC-01 and 16 to placebo. No deaths or major adverse cardiac events were reported at 12 months. One severe adverse events in each group was considered possibly related to study treatment (allergic dermatitis and rash). AlloCSC-01 elicited low levels of donor-specific antibodies in 2 patients. No immune-related adverse events were found, and no differences between groups were observed in magnetic resonance-based efficacy parameters at 12 months. The estimated treatment effect of AlloCSC-01 on the absolute change from baseline in infarct size was -2.3% (95% confidence interval, -6.5% to 1.9%).AlloCSC-01 can be safely administered in ST-segment-elevation myocardial infarction patients with left ventricular dysfunction early after revascularization. Low immunogenicity and absence of immune-mediated events will facilitate adequately powered studies to demonstrate their clinical efficacy in this setting.URL: http://www.clinicaltrials.gov . Unique identifier: NCT02439398.

© 2016 The Author(s). Pseudomonas has the highest number of species out of any genus of Gram-negative bacteria and is phylogenetically divided into several groups. The Pseudomonas putida phylogenetic branch includes at least 13 species of environmental and industrial interest, plant-associated bacteria, insect pathogens, and even some members that have been found in clinical specimens. In the context of the Genomic Encyclopedia of Bacteria and Archaea project, we present the permanent, high-quality draft genomes of the type strains of 3 taxonomically and ecologically closely related species in the Pseudomonas putida phylogenetic branch: Pseudomonas fulva DSM 17717T, Pseudomonas parafulva DSM 17004Tand Pseudomonas cremoricolorata DSM 17059T. All three genomes are comparable in size (4.6-4.9Mb), with 4,119-4,459 protein-coding genes. Average nucleotide identity based on BLAST comparisons and digital genome-to-genome distance calculations are in good agreement with experimental DNA-DNA hybridization results. The genome sequences presented here will be very helpful in elucidating the taxonomy, phylogeny and evolution of the Pseudomonas putida species complex.