Extracellular vesicles (EVs) are membranous nanostructures that can indicate undergoing processes in organs and thus help in diagnostics and prognostics. They are secreted by all cells, contained in body fluids, and able to transfer proteins, lipids and nucleic acids to distant cells. Intracranial EVs were shown to change their composition after severe traumatic brain injury (TBI) and therefore to have biomarker potential to evaluate brain events. Properties of intracranial EVs early after TBI, however, have not been characterized. Here, we assessed cerebrospinal fluid (CSF) up to seven days after isolated severe TBI for physical properties of EVs and their proteins associated with neuroregeneration. These findings were compared with healthy controls and correlated to patient outcome. The study included 17 patients with TBI and 18 healthy controls. EVs in TBI-CSF were visualized by electron microscopy and confirmed by immunoblotting for membrane associated Flotillin-1 and Flotillin-2. Using nanoparticle tracking analysis, we detected the highest range in EV concentration at day 1 after injury and significantly increased EV size at days 4-7. CSF concentrations of neuroregeneration associated proteins Flotillin-1, ADP-ribosylation Factor 6 (Arf6), and Ras-related protein Rab7a (Rab7a) were monitored by enzyme-linked immunosorbent assays. Flotillin-1 was detected solely in TBI-CSF in about one third of tested patients. Unfavorable outcomes included decreasing Arf6 concentrations and a delayed Rab7a concentration increase in CSF. CSF concentrations of Arf6 and Rab7a were negatively correlated. Our data suggest that the brain response within several days after severe TBI includes shedding of EVs associated with neuroplasticity. Extended studies with a larger number of participants and CSF collected at shorter intervals are necessary to further evaluate neuroregeneration biomarker potential of Rab7a, Arf6, and Flotillin-1.
Introduction: Traumatic brain injury is the leading cause of death in children and adults in developed countries. Severe traumatic brain injury is classified with Glasgow Coma Scale score 8 and less. About 50% of patients with severe traumatic brain injury developes at least one infection as a complication of primary condition during hospitalization in the Intensive Care Unit, resulting with fatal outcome in 28% of patients. Ventilator-associated pneumonia is the leading infection that affects patients with severe traumatic brain injury, with an incidence between 41% and 74%. Following are sepsis and urinary tract infections. The aim: To analyze the number of patients with nosocomial infection and isolated severe traumatic brain injury hospitalized in the Intensive Care Unit of the Clinical Hospital Centre Rijeka, Croatia, from 31 st January 2013 to 31 st December 2014. Patients and methods: A two-year retrospective study included 46 patients with isolated severe traumatic brain injury and nosocomial infection hospitalized in the Intensive Care Unit of the Clinical Hospital Centre Rijeka,Croatia, in the period from 31 st January 2013 to 31 st December 2014. All medical data was collected from the Division of Intensive Care Unit, Clinical Hospital Centre Rijeka, Croatia. Results: From 67 patients with isolated severe traumatic brain injury, 46 (68,65%) of them developed nosocomial infection. There was statistically significant more male patients than female (p < 0.05). The average age of infected patients was 57,8 years. The leading were the infections of the respiratory system. Gram-negative bacteria Proteus mirabilis and Pseudomonas aerugnonsa were the leading pathogens. The average duration of the infection was 5,77 day. Duration of mechanical ventilation accounted for the majority of the patients more than 10 days. The average duration of treatment for all 46 patients was 10,475 days, and for 16 (34,78%) of them, the treatment outcome was lethal. Conclusion: Nosocomial infections are becoming a major public health problem. The emphasis must be set on the prevention which includes maintaining the hygiene and the antiseptic rules among the medical personnel of the Intensive Care Unit. Already developed infections must be adequately treated so the negative treatment outcomes can be reduced.
PurposeTo describe data on epidemiology, microbiology, clinical characteristics and outcome of adult ICU patients with secondary peritonitis, with special emphasis on antimicrobial therapy and source control. Methods Post hoc analysis of a multicenter observational study (Abdominal Sepsis Study, AbSeS ) including 2621 adult ICU patients with intra-abdominal infection in 306 ICUs from 42 countries. Time-till-source control intervention was calculated as from time of diagnosis and classified into 'emergency' (<2 hours), 'urgent' (2-6 hours), and 'delayed' (>6 hours). Relationships were assessed by logistic regression analysis and reported as odds ratios (OR) and [95% confidence interval]. ResultsThe cohort included 1077 cases of microbiologically confirmed secondary peritonitis. Mortality was 29.7%. The rate of appropriate empiric therapy showed no difference between survivors and non-survivors (66.4% vs . 61.3%, p=0.102). A stepwise increase in mortality was observed with increasing SOFA scores (19.6% for a value £4 to 55.4% for a value >12, p<0.001). The highest odds of death were associated with septic shock .00]), late-onset hospital-acquired peritonitis ) and failed source control evidenced by persistent inflammation at Day 7 ). Compared with 'emergency' source control intervention (<2 hours of diagnosis), 'urgent' source control was the only modifiable covariate associated with lower odds of mortality ). Conclusions 'Urgent' and successful source control were associated with improved odds of survival. Appropriateness of empirical antimicrobial treatment did not significantly affect survival suggesting that source control is more determinative for outcome.
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