Mitochondrial DNA depletion induces innate immune dysfunction rescued by interferon-γ

Monocytes from sepsis patients have mitochondrial DNA (mtDNA) depletion and immune deactivation. Here we find that THP-1 cell immune responses are impaired by experimentally depleting mtDNA, through dysregulated immune signalling, and rescued by interferon-γ treatment

Pyogenic brain abscess and subdural empyema: presentation, management, and factors predicting outcome

\ua9 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: To describe the presentation and management of bacterial brain abscess and subdural empyema in adults treated at two tertiary centers. In addition, to identify factors that may predict a poor clinical outcome. Methods: A retrospective analysis of data obtained from clinical records was performed, followed by multivariate regression analysis of patient and treatment-related factors. Results: 113 patients were included with a median age of 53 years and a male preponderance. At presentation symptoms were variable, 28% had a focal neurological deficit, and 39% had a reduced Glasgow coma scale (GCS). Brain abscesses most frequently affected the frontal, temporal, and parietal lobes while 36% had a subdural empyema. An underlying cause was identified in 76%; a contiguous ear or sinus infection (43%), recent surgery or trauma (18%) and haematogenous spread (15%). A microbiological diagnosis was confirmed in 86%, with streptococci, staphylococci, and anaerobes most frequently isolated. Treatment involved complex, prolonged antibiotic therapy (> 6 weeks in 84%) combined with neurosurgical drainage (91%) and source control surgery (34%). Mortality was 5% with 31% suffering long-term disability and 64% achieving a good clinical outcome. A reduced GCS, focal neurological deficit, and seizures at presentation were independently associated with an unfavorable clinical outcome (death or disability). Conclusions: Complex surgical and antimicrobial treatment achieves a good outcome in the majority of patients with bacterial brain abscess and subdural empyema. Factors present at diagnosis can help to predict those likely to suffer adverse outcomes. Research to determine optimal surgical and antibiotic management would be valuable

Randomised controlled trial of GM-CSF in critically ill patients with impaired neutrophil phagocytosis

Background Critically ill patients with impaired neutrophil phagocytosis have significantly increased risk of nosocomial infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) improves phagocytosis by neutrophils ex vivo. This study tested the hypothesis that GM-CSF improves neutrophil phagocytosis in critically ill patients in whom phagocytosis is known to be impaired. Methods This was a multicentre, phase IIa randomised, placebo-controlled clinical trial. Using a personalised medicine approach, only critically ill patients with impaired neutrophil phagocytosis were included. Patients were randomised 1:1 to subcutaneous GM-CSF (3 μg/kg/day) or placebo, once daily for 4 days. The primary outcome measure was neutrophil phagocytosis 2 days after initiation of GM-CSF. Secondary outcomes included neutrophil phagocytosis over time, neutrophil functions other than phagocytosis, monocyte HLA-DR expression and safety. Results Thirty-eight patients were recruited from five intensive care units (17 randomised to GM-CSF). Mean neutrophil phagocytosis at day 2 was 57.2% (SD 13.2%) in the GM-CSF group and 49.8% (13.4%) in the placebo group, p=0.73. The proportion of patients with neutrophil phagocytosis≥50% at day 2, and monocyte HLA-DR, appeared significantly higher in the GM-CSF group. Neutrophil functions other than phagocytosis did not appear significantly different between the groups. The most common adverse event associated with GM-CSF was fever. Conclusions GM-CSF did not improve mean neutrophil phagocytosis at day 2, but was safe and appeared to increase the proportion of patients with adequate phagocytosis. The study suggests proof of principle for a pharmacological effect on neutrophil function in a subset of critically ill patients