Background Neuroinflammation following traumatic brain injury (TBI) has been shown to be associated with secondary injury development; however, how systemic inflammatory mediators affect this is not fully understood. The aim of this study was to see how systemic inflammation affects markers of neuroinflammation, if this inflammatory response had a temporal correlation between compartments and how different compartments differ in cytokine composition. Methods TBI patients recruited to a previous randomised controlled trial studying the effects of the drug anakinra (Kineret®), a human recombinant interleukin-1 receptor antagonist (rhIL1ra), were used (n = 10 treatment arm, n = 10 control arm). Cytokine concentrations were measured in arterial and jugular venous samples twice a day, as well as in microdialysis-extracted brain extracellular fluid (ECF) following pooling every 6 h. C-reactive protein level (CRP), white blood cell count (WBC), temperature and confirmed systemic clinical infection were used as systemic markers of inflammation. Principal component analyses, linear mixed-effect models, cross-correlations and multiple factor analyses were used. Results Jugular and arterial blood held similar cytokine information content, but brain-ECF was markedly different. No clear arterial to jugular gradient could be seen. No substantial delayed temporal associations between blood and brain compartments were detected. The development of a systemic clinical infection resulted in a significant decrease of IL1-ra, G-CSF, PDGF-ABBB, MIP-1b and RANTES (p < 0.05, respectively) in brain-ECF, even if adjusting for injury severity and demographic factors, while an increase in several cytokines could be seen in arterial blood. Conclusions Systemic inflammation, and infection in particular, alters cytokine levels with different patterns seen in brain and in blood. Cerebral inflammatory monitoring provides independent information from arterial and jugular samples, which both demonstrate similar information content. These findings could present potential new treatment options in severe TBI patients, but novel prospective trials are warranted to confirm these associations. Graphical abstract
ore than 9 million burn injuries annually are severe enough to require medical attention. The World Health Organization burn mortality estimates have been as high as 180,000 annually. 1,2 Burn incidence surpasses that of infectious diseases such as tuberculosis or human immunodeficiency virus infection. 3 Although the global burden of disease attributable to burns is significant, it is disproportionately greater in low-and middle-income countries (LMICs), which account for 90% of deaths attributable to burns. 4 Within all countries, poverty increases the likelihood of burn injuries and death; this is even more pronounced when there are disparities in countrywide income leading to socioeconomically disadvantaged populations.Background: Standardized estimates of global economic losses from burn injuries are lacking. The primary objective of this study was to determine the global macroeconomic consequences of burn injuries and their geographic distribution. Methods: Using the Institute of Health Metrics and Evaluation database (2009 and 2019), mean and 95% uncertainty interval (UI) data on incidence, mortality, and disability-adjusted life-years (DALYs) from injuries caused by fire, heat, and hot substances were collected. Gross domestic product (GDP) data were analyzed together with DALYs to estimate macroeconomic losses globally using a value of lost welfare approach. Results: There were 9 million global burn cases (95% UI, 6.8 to 11.2 million) and 111,000 deaths from burns (95% UI, 88,000 to 132,000 deaths) in 2019, representing a total of 7.5 million DALYs (95% UI, 5.8 to 9.5 million DALYs). This represented welfare losses of $112 billion (95% UI, $78 to $161 billion), or 0.09% of GDP (95% UI, 0.06% to 0.13%). Welfare losses as a share of GDP were highest in low-and middle-income countries (LMICs) of Oceania (0.24%; 95% UI, 0.09% to 0.42%) and Eastern Europe (0.24%; 95% UI, 0.19% to 0.30%) compared with high-income country regions such as Western Europe (0.06%; 95% UI, 0.04% to 0.09%). Mortality-incidence ratios were highest in LMIC regions, highlighting a lack of treatment access, with southern sub-Saharan Africa reporting a mortalityincidence ratio of 40.1 per 1000 people compared with 1.9 for Australasia. Conclusions: Burden of disease and resulting economic losses because of burn injuries are substantial worldwide and are disproportionately higher in LMICs. Possible effective solutions include targeted education, advocacy, and legislation to decrease incidence and investing in existing burn centers to improve treatment access.
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