What the fuck good does describing a problem do when you offer no solution? I would have been fired in no time in any of my programming jobs if I attempted that crapola.
Secondary injury and inflammation after intracerebral haemorrhage: a systematic review and meta-analysis of molecular markers in patient brain tissue
Abstract
Background Inflammatory responses to intracerebral haemorrhage (ICH) are potential therapeutic targets. We aimed to quantify molecular markers of inflammation in human brain tissue after ICH compared with controls using meta-analysis.
Methods We searched OVID MEDLINE (1946–) and Embase (1974–) in June 2020 for studies that reported any measure of a molecular marker of inflammation in brain tissue from five or more adults after ICH. We assessed risk of bias using a modified Newcastle-Ottawa Scale (mNOS; mNOS score 0–9; 9 indicates low bias), extracted aggregate data, and used random effects meta-analysis to pool associations of molecules where more than two independent case–control studies reported the same outcome and Gene Ontology enrichment analysis to identify over-represented biological processes in pooled sets of differentially expressed molecules (International Prospective Register of Systematic Reviews ID: CRD42018110204).
Results Of 7501 studies identified, 44 were included: 6 were case series and 38 were case–control studies (median mNOS score 4, IQR 3–5). We extracted data from 21 491 analyses of 20 951 molecules reported by 38 case–control studies. Only one molecule (interleukin-1β protein) was quantified in three case–control studies (127 ICH cases vs 41 ICH-free controls), which found increased abundance of interleukin-1β protein after ICH (corrected standardised mean difference 1.74, 95% CI 0.28 to 3.21, p=0.036, I2=46%). Processes associated with interleukin-1β signalling were enriched in sets of molecules that were more abundant after ICH.
Conclusion Interleukin-1β abundance is increased after ICH, but analyses of other inflammatory molecules after ICH lack replication. Interleukin-1β pathway modulators may optimise inflammatory responses to ICH and merit testing in clinical trials.
Data availability statement
Analysis scripts will be shared on contact with the corresponding author after publication. Gene sets derived from human RNAseq analyses may be available to reasonable requests with appropriate ethical approval. Data for the meta-analysis dataset were extracted from published reports or provided by their corresponding authors.
This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
Introduction
Stroke due to spontaneous intracerebral haemorrhage (ICH) causes substantial death and disability.1 There are no effective specific medical treatments for ICH.2
Brain inflammation is a potential therapeutic target after ICH. Much of our understanding of the inflammatory response in the brain after ICH has been informed by studies of animal models.3 In rodent models, modulators of inflammatory responses to ICH can be used to improve functional outcome.3 Although animal models provide useful mechanistic insights, there are significant differences in immune physiology, haemorrhage induction and haemorrhage evolution between humans and rodents with ICH.4 5 To aid in the design and selection of interventions for clinical trials that translate the benefits of interventions tested in experimental ICH into humans, greater knowledge of disease processes in humans after ICH is needed.
To identify potential therapeutic targets for ICH, we conducted a systematic review and meta-analysis of inflammation in human brain tissue following ICH with three aims: first, to identify all molecular measures of inflammation reported by published studies of ICH in human brain tissue; second, to quantify pooled associations between individual molecules and ICH compared with controls; and third, to identify associations between ICH and groups of molecules with similar functions, compared with controls.
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