No abstract

M-MDSCs and G-MDSCs strongly contribute to T-cell dysfunction in patients with sepsis. More specifically, G-MDSCs producing arginase 1 are associated with a higher incidence of nosocomial infections and seem to be major actors of sepsis-induced immune suppression.

This study found a high frequency of laryngeal injuries after extubation in ICU, which were associated with intubation duration and patient's height/ETT size ratio. Edema was not the only injury responsible for PES, and although edema is frequent it is not the only injury associated with reintubation.

Exaggerated release of neutrophil extracellular traps (NETs) along with decreased NET clearance and inability to remove apoptotic cells (efferocytosis) may contribute to sustained inflammation in acute respiratory distress syndrome (ARDS). Recent studies in experimental models of ARDS have revealed the crosstalk between AMP-activated protein kinase (AMPK) and high-mobility group box 1 (HMGB1), which may contribute to effectiveness of efferocytosis, thereby reducing inflammation and ARDS severity.We investigated neutrophil and NET clearance by macrophages from control and ARDS patients and examined how bronchoalveolar lavage (BAL) fluid from control and ARDS patients could affect NET formation and efferocytosis. Metformin (an AMPK activator) and neutralising antibody against HMGB1 were applied to improve efferocytosis and NET clearance.Neutrophils from ARDS patients showed significantly reduced apoptosis. Conversely, NET formation was significantly enhanced in ARDS patients. Exposure of neutrophils to ARDS BAL fluid promoted NET production, while control BAL fluid had no effect. Macrophage engulfment of NETs and apoptotic neutrophils was diminished in ARDS patients. Notably, activation of AMPK in macrophages or neutralisation of HMGB1 in BAL fluid improved efferocytosis and NET clearance.In conclusion, restoration of AMPK activity with metformin or specific neutralisation of HMGB1 in BAL fluid represent promising therapeutic strategies to decrease sustained lung inflammation during ARDS.

Although AMPK plays well-established roles in the modulation of energy balance, recent studies have shown that AMPK activation has potent anti-inflammatory effects. In the present experiments, we examined the role of AMPK in phagocytosis. We found that ingestion of Escherichia coli or apoptotic cells by macrophages increased AMPK activity. AMPK activation increased the ability of neutrophils or macrophages to ingest bacteria (by 46 ± 7.8 or 85 ± 26%, respectively, compared to control, P<0.05) and the ability of macrophages to ingest apoptotic cells (by 21 ± 1.4%, P<0.05 compared to control). AMPK activation resulted in cytoskeletal reorganization, including enhanced formation of actin and microtubule networks. Activation of PAK1/2 and WAVE2, which are downstream effectors of Rac1, accompanied AMPK activation. AMPK activation also induced phosphorylation of CLIP-170, a protein that participates in microtubule synthesis. The increase in phagocytosis was reversible by the specific AMPK inhibitor compound C, siRNA to AMPKα1, Rac1 inhibitors, or agents that disrupt actin or microtubule networks. In vivo, AMPK activation resulted in enhanced phagocytosis of bacteria in the lungs by 75 ± 5% vs. control (P<0.05). These results demonstrate a novel function for AMPK in enhancing the phagocytic activity of neutrophils and macrophages.

Significant advances in brain imaging, minimally invasive neurosurgery, molecular biology and antibacterial agents have dramatically improved the prognosis of brain abscess in immunocompetent patients over the last decades.

No abstract

To assess energy balance in very sick medical patients requiring prolonged acute mechanical ventilation and its possible impact on outcome, we conducted an observational study of the first 14 d of intensive care unit (ICU) stay in thirty-eight consecutive adult patients intubated at least 7 d. Exclusive enteral nutrition (EN) was started within 24 h of ICU admission and progressively increased, in absence of gastrointestinal intolerance, to the recommended energy of 125·5 kJ/kg per d. Calculated energy balance was defined as energy delivered 2 resting energy expenditure estimated by a predictive method based on static and dynamic biometric parameters. Mean energy balance was 25439 (SEM 222) kJ per d. EN was interrupted 23 % of the time and situations limiting feeding administration reached 64 % of survey time. ICU mortality was 72 %. Non-survivors had higher mean energy deficit than ICU survivors (P¼ 0·004). Multivariate analysis identified mean energy deficit as independently associated with ICU death (P¼0·02). Higher ICU mortality was observed with higher energy deficit (P¼ 0·003 comparing quartiles). Using receiver operating characteristic curve analysis, the best deficit threshold for predicting ICU mortality was 5021 kJ per d. Kaplan -Meier analysis showed that patients with mean energy deficit^5021 kJ per d had a higher ICU mortality rate than patients with lower mean energy deficit after the 14th ICU day (P¼ 0·01). The study suggests that large negative energy balance seems to be an independent determinant of ICU mortality in a very sick medical population requiring prolonged acute mechanical ventilation, especially when energy deficit exceeds 5021 kJ per d. Energy balance: Enteral nutrition: Acute prolonged mechanical ventilation: OutcomeNutritional support is based on the assumption that critically ill patients are prone to develop malnutrition, especially protein-energy deficit, this condition being associated with morbidity and mortality (1 -5) . Indeed, protein-energy deficit seems common in intensive care units (ICU), occurring in 43 -88 % of critically ill patients (6,7) . Underfeeding has been reported as associated with an increased rate of infection, poor wound healing, reduced respiratory muscle mass, delayed weaning from mechanical ventilation, increased length of ICU stay and increased health care costs (1,8 -13) . Perturbations of the normal metabolic response to starvation with hyperglycaemia, high lactate level, hypertriglyceridaemia and high NEFA concentrations due to insulin resistance characterize the hypermetabolic state of the critically injured patients (2,14,15) . Energy deficit results from a combination of hypermetabolism and reduced intake due to frequent interruptions in feedings because of gastrointestinal intolerance, diagnostic and therapeutic procedures (16 -18) . In intubated and mechanically ventilated patients, the great variability of resting energy expenditure (REE) and nutrient delivery compared to prescription, partly due to frequent use of sedatives, analgesic...