Response to Chemoimmunotherapy Is Associated With Expansion of Systemic Antitumor CD4 + Th1 Response in Metastatic Non-Small Cell Lung Cancer.

Limited data have reported the evolution of antitumor immune responses under chemoimmunotherapy (chemo-IO) in patients with metastatic non-small cell lung cancer. In this concise study, we performed dynamic monitoring of antitumor CD4 + T helper 1 (Th1) response in peripheral blood from 12 patients receiving a first-line chemo-IO. Tumor-reactive CD4 + Th1 cells were assessed within blood lymphocytes using interferon-gamma enzyme-linked immunospot assay to detect telomerase (TERT)-specific T cells at baseline, 3 and 12 months after treatment. An induction of circulating anti-TERT CD4 + Th1 response were found in 6 of 12 patients at 3 months after chemo-IO. In contrast, 3 patients had a substantial decrease in their preexisting response and 3 remained nonimmune responders. Among patients with chemo-IO-induced immune response, half achieved an objective clinical response and had long-lasting circulating anti-TERT CD4 + Th1 cells detected for at least 1 year. In contrast, no objective response was documented in nonimmune responders and a link between the loss of anti-TERT CD4 + Th1 responses were observed in patients with progressive disease. This preliminary work supports a relationship between the efficacy of combinatorial chemo-IO and circulating anti-TERT CD4 + Th1 responses and highlights the interest to implement blood-based monitoring of tumor-reactive CD4 + T cells that could be additional help for patient management.

Outcome of methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia: impact of diabetes.

The aim of this study was to describe the epidemiology of methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia in a diabetic and a non-diabetic population of the University Hospital of Charleroi and to analyze medical outcomes, including risk of metastatic infection and mortality. Descriptive and multivariable analyses were performed using MedCalc 18.9 (MedCalc Software bvba, Ostend, Belgium). A total of 248 patients with MSSA bacteremia were identified between 1st January 2012 and 28th June 2017 out of which 32.7% were diabetic. Within the diabetic patients, we observed more prolonged hospital duration of stay (p = 0.034), more secondary bacteremia of cutaneous sources (including cellulitis, diabetic foot and ulcer) (p = 0.037), and more metastatic infection (p = 0.002). The overall 30-day mortality was 24.2% with no difference between the two groups. With a logistic regression analysis, it was demonstrated that age ≥ 60 years (odds ratio (OR), 2.20 (95% CI, 1.03-4.67)) and Charlson Comorbidity Index (CCI) ≥ 3 (OR, 2.95 (95% CI, 1.51-5.79)) were the only independent risk factors of mortality, while removal of the primary site of infection was a protective factor (OR, 0.27 (95% CI, 0.12-0.62)). Risk of developing metastatic infection was increased with diabetes (OR, 2.08 (95% CI, 1.12-3.90)), while early empirical antibiotic therapy (OR, 0.38 (95% CI, 0.20-0.71)) decreased this risk. Diabetes was not associated with increased 30-day mortality after MSSA bacteremia. However, diabetes increased significantly the risk of metastatic infection. An aggressive treatment of MSSA bacteremia seems crucial to improve the outcome of diabetic patients.

Neuraminidase alters red blood cells in sepsis.

OBJECTIVE: To investigate the influence of neuraminidase, an enzyme that cleaves sialic acid from the red blood cell (RBC) membrane, on RBC shape and biochemistry in critically ill patients. DESIGN: Prospective, observational study and in vitro laboratory study. SETTING: A 31-bed medico-surgical department of intensive care and a university-affiliated cell biology laboratory. SUBJECTS: Acutely ill patients with and without sepsis and healthy volunteers. INTERVENTIONS: Blood sampling in volunteers. MEASUREMENTS AND MAIN RESULTS: Neuraminidase activity was measured using a fluorescent assay. RBC shape was assessed by the second coefficient of dissymmetry of Pearson using a flow cytometry technique at 25 degrees C. Intraerythrocytic 2,3-diphosphoglycerate and lactate contents were also measured. Neuraminidase activity was significantly higher in septic patients compared with nonseptic patients and healthy volunteers (5.42 [4.85-6.00] vs. 4.53 [4.23-5.23] and 1.26 [0.83-1.83] mU/mL; all p < 0.05). Neuraminidase treatment modified the RBC shape in vitro in a dose-response fashion, and most of these alterations were present after 10 hours of incubation. Incubation of RBCs with phosphatidylinositol phospholipase C modified RBC shape and increased sialic acid concentrations in the supernatant, suggesting a leakage of neuraminidase from the RBC membrane. Alterations in shape were associated with increased 2,3-diphosphoglycerate (0.46 +/- 0.25 vs. 0.19 +/- 0.05 mumol/mL; p = 0.006) and lactate content (0.81 +/- 0.07 vs. 0.66 +/- 0.05 mmoL/L; p = 0.002). CONCLUSIONS: In sepsis, desialylation under the influence of increased neuraminidase activity may contribute to the alterations in RBC rheology. Inhibition of neuraminidase may represent a new therapeutic option to ameliorate RBC rheology and perhaps oxygen delivery to the cells.