Granulocytic myeloid-derived suppressor cells inversely correlate with plasma arginine and overall survival in critically ill patients.

Critically ill patients display a state of immunosuppression that has been attributed in part to decreased plasma arginine concentrations. However, we and other authors have failed to demonstrate a clinical benefit of L-arginine supplementation. We hypothesize that, in these critically ill patients, these low plasma arginine levels may be secondary to the presence of granulocytic myeloid-derived suppressor cells (gMDSC), which express arginase known to convert arginine into nitric oxide (NO) and citrulline. Indeed, in a series of 28 non-surgical critically ill patients, we showed a dramatic increase in gMDSC compared to healthy subjects (P = 0·0002). A significant inverse correlation was observed between arginine levels and gMDSC (P = 0·01). As expected, gMDSC expressed arginase preferentially in these patients. Patients with high gMDSC levels on admission to the medical intensive care unit (MICU) presented an increased risk of death at day 7 after admission (P = 0·02). In contrast, neither plasma arginine levels, monocytic MDSC levels nor neutrophil levels were associated with overall survival at day 7. No relationship was found between body mass index (BMI) or simplified acute physiology score (SAPS) score, sequential organ failure assessment (SOFA) score or gMDSC levels, eliminating a possible bias concerning the direct prognostic role of these cells. As gMDSC exert their immunosuppressive activity via multiple mechanisms [production of prostaglandin E2 (PGE2 ), interleukin (IL)-10, arginase, etc.], it may be more relevant to target these cells, rather than simply supplementing with L-arginine to improve immunosuppression and its clinical consequences observed in critically ill patients.

Assessment of five screening strategies for optimal detection of carriers of third-generation cephalosporin-resistant Enterobacteriaceae in intensive care units using daily sampling.

There is no consensus on optimal screening procedures for multidrug-resistant Enterobacteriaceae (MDRE) in intensive care units (ICUs). Therefore, we assessed five strategies for the detection of extended-spectrum beta-lactamase (ESBL) and high-level expressed AmpC cephalosporinase (HL-CASE) producers. During a 3-month period, a rectal screening swab sample was collected daily from every ICU patient, from the first 24 h to the last day of ICU stay. Samples were plated on MDRE-selective media. Bacteria were identified using MALDI-TOF mass spectrometry and antibiograms were performed using disk diffusion. MDREs were isolated from 682/2348 (29.0%) screening samples collected from 93/269 (34.6%) patients. Incidences of patients with ESBL and HL-CASE producers were 17.8 and 19.3 per 100 admissions, respectively. In 48/93 patients, MDRE carriage was intermittent. Compared with systematic screening at admission, systematic screening at discharge did not significantly increase the rate of MDRE detection among the 93 patients (62% vs. 70%). In contrast, screening at admission and discharge, screening at admission and weekly thereafter, and screening at admission and weekly thereafter and at discharge significantly increased MDRE detection (77%, p 0.02; 76%, p 0.01; 86%, p<0.001, respectively). The difference in MDRE detection between these strategies relies essentially on the levels of detection of patients with HL-CASE producers. The most reasonable strategy would be to collect two samples, one at admission and one at discharge, which would detect 87.5% of the ESBL strains, 67.3% of the HL-CASE strains and 77.4% of all MDRE strains. This study should facilitate decision-making concerning the most suitable screening policy for MDRE detection in a given ICU setting.

Comparison of five media for detection of extended-spectrum Beta-lactamase by use of the wasp instrument for automated specimen processing.

Overall, 2,337 rectal screening samples (RSSs) were seeded by using the Wasp instrument for automated microbiological processing with five media for detection of extended-spectrum ß-lactamase (ESBL): CHROMagar, ChromID, Brilliance, BD Drigalski, and HEGP media. Of 354 RSSs harboring ESBL-producing isolates, 89.3% were found to be positive on all media. Sensitivity and specificity ranged from 95.5 to 98.3% and from 57.9 to 72.3%, respectively. No medium was perfectly ESBL selective, and non-ESBL-producing strains were mainly Enterobacteriaceae overproducing AmpC ß-lactamase and nonfermenting Gram-negative bacilli, mostly Pseudomonas aeruginosa.

Risk factors and clinical outcome of unsuspected pulmonary embolism in cancer patients: a case-control study.

BACKGROUND: Little is known about the risk factors and outcome of unsuspected pulmonary embolism (UPE) in cancer patients. OBJECTIVES: To assess the risk factors and outcome of UPE in cancer patients. METHODS: The charts of 66 patients diagnosed with UPE were reviewed. Two control groups were selected: 132 cancer patients without pulmonary embolism (PE) and 65 cancer patients with clinically suspected PE. Variables associated with UPE were identified by multivariable analysis. Six-month survival and recurrent venous thromboembolism were compared by use of Cox proportional analysis. RESULTS: Twenty-seven (40.9%) patients with UPE had symptoms suggesting PE. Adenocarcinoma (odds ratio [OR] 4.45; 95% confidence interval [CI] 1.98-9.97), advanced age (OR 1.18; 95% CI 1.02-1.38), recent chemotherapy (OR 4.62; 95% CI 2.26-9.44), performance status > 2 (OR 7.31; 95% CI 1.90-28.15) and previous venous thromboembolism (OR 4.47; 95% CI 1.16-17.13) were associated with UPE. When adjusted for tumor stage and performance status, 6-month mortality did not differ between patients with UPE and patients without PE (hazard ratio 1.40; 95% CI 0.53-3.66; P = 0.50). Patients with UPE were more likely to have central venous catheters and chemotherapy and less likely to have proximal clots than patients with clinically suspected PE. Recurrent venous thromboembolism occurred in 6.1% and 7.7% of patients with UPE and symptomatic PE, respectively. CONCLUSION: UPE is not associated with an increased risk of death. Patients with clinically suspected PE and those with UPE have similar risks of recurrent venous thromboembolism.