Nutritional therapy and infectious diseases: a two-edged sword

The benefits and risks of nutritional therapies in the prevention and management of infectious diseases in the developed world are reviewed. There is strong evidence that early enteral feeding of patients prevents infections in a variety of traumatic and surgical illnesses. There is, however, little support for similar early feeding in medical illnesses. Parenteral nutrition increases the risk of infection when compared to enteral feeding or delayed nutrition. The use of gastric feedings appears to be as safe and effective as small bowel feedings. Dietary supplementation with glutamine appears to lower the risk of post-surgical infections and the ingestion of cranberry products has value in preventing urinary tract infections in women

Determination of MICING

Our work was focused on a new assay for characterising clinically important yeast. This assay was developed due to the need for new diagnostic methods for recognising potentially virulent strains of increasingly important non-albicans yeast pathogens, such as Saccharomyces cerevisiae and Candida glabrata. With the great diversity among strains for virulence and virulence factors, identification to the species level is not sufficienttherefore, testing for specific virulent traits remains the best option. We show here that the proposed assay uncovers the relationships between the three most important yeast virulence traits in a single test: the ability of a strain to invade solid medium, while resisting the presence of an antimycotic and high temperature (37 °C). We combined the quantitative agar invasion assay with classical antimycotic susceptibility testing into a single assay. Similarly to the minimal inhibitory concentration (MIC) value, we defined the MICING (minimal inhibitory concentration of antimycotic for invasive growth) as the concentration of an antimycotic above which the yeast invasive growth is significantly repressed. In this study, we tested three of the most common antimycotics: fluconazole, itraconazole and amphotericin B. The response of yeast strains invasion was characteristic of each antimycotic, indicating their mechanisms of action. In addition to MICING, the assay provides quantitative information about the superficial and invasive growth, and also about the relative invasion, which helps in identifying clinically important yeast, such as azole-resistant and/or invasive strains of S. cerevisiae and C. glabrata

Immunohistochemical evaluation of two antibodies against PD-L1 and prognostic significance of PD-L1 expression in epithelioid peritoneal malignant mesothelioma: A RENAPE study

International audienceBACKGROUND:Epithelioid peritoneal malignant mesothelioma (EPMM) is the most common subtype of this aggressive tumor. We compared two antibodies against PD-L1, a recent theranostic biomarker, and evaluated the prognostic value of PD-L1 expression by mesothelial and immune cells in EPMM.METHODS:Immunohistochemistry was performed on 45 EPMM. Clinical and pathological data were extracted from the RENAPE database. Using E1L3N and SP142 clones, inter-observer agreement, PD-L1 expression by mesothelial and immune cells and inter-antibody agreement were evaluated. The prognostic relevance of PD-L1 expression was evaluated in 39 EPMM by univariate and multivariate analysis of overall survival (OS) and progression-free survival (PFS).RESULTS:Inter-observer agreement on E1L3N immunostaining was moderate for mesothelial and immune cells, and fair for mesothelial and poor for immune cells using SP142. Using E1L3N, 31.1% of mesothelial and 15.6% of immune cells expressed PD-L1, and 22.2% of mesothelial and 26.7% of immune cells using SP142. Inter-antibody agreement was moderate. In most positive cases, 1-5% of tumor cells were positive. Using E1L3N, PD-L1 expression by lymphocytes was associated with better OS and PFS by both univariate and multivariate analysis. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy predicted better prognosis than other treatments. Solid subtype was an independent prognostic factor for worse OS.CONCLUSION:E1L3N appeared easier to use than SP142 to evaluate PD-L1 expression. A minority of EPMM expressed PD-L1, and only a few cells were positive. PD-L1 expression by immune cells evaluated with E1L3N was an independent prognostic factor in EPMM

RECOMBINANT HUMAN INTERLEUKIN-1 RECEPTOR ANTAGONIST IN THE TREATMENT OF PATIENTS WITH SEPSIS SYNDROME - RESULTS FROM A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

Objective.-To further define the safety and efficacy of recombinant human interleukin 1 receptor antagonist (rhlL-1ra) in the treatment of sepsis syndrome. Study Design.-Randomized, double-blind, placebo-controlled, multicenter, multinational clinical trial. Population.-A total of 893 patients with sepsis syndrome received an intravenous loading dose of rhIL-1ra, 100 mg, or placebo followed by a continuous 72-hour intravenous infusion of rhIL-1ra (1.0 or 2.0 mg/kg per hour) or placebo. Outcome Measure.-Twenty-eight-day all-cause mortality. Results.-There was not a significant increase in survival time for rhIL-1ra treatment compared with placebo among all patients who received the study medication (n=893; generalized Wilcoxon statistic, P=.22) or among patients with shock at study entry (n=713; generalized Wilcoxon statistic, P=.23), the two primary efficacy analyses specified a priori for this trial. Results from secondary analyses suggest an increase in survival time with rhIL-1ra treatment among patients with dysfunction of one or more organs (n=563; linear dose-response, P=.009). Retrospective analysis demonstrated an increase In survival time with rhIL-1ra treatment among patients with a predicted risk of mortality of 24% or greater (n=580; linear dose-response, P=.005) as well as among patients with both dysfunction of one or more organs and a predicted risk of mortality of 24% or greater (n=411; linear dose-response, P=.002). Conclusions.-There was not a statistically significant increase in survival time for rhIL-1ra treatment compared with placebo among all patients who received the study medication or among patients with shock at study entry. Secondary and retrospective analyses of efficacy suggest that treatment with rhIL-1ra results in a dose-related increase in survival time among patients with sepsis who have organ dysfunction and/or a predicted risk of mortality of 24% or greate