Alcohol-related liver disease (ALD) is a major cause of liver-related death worldwide, yet understanding of the three key pathological features of the disease—fibrosis, inflammation and steatosis—remains incomplete. Here, we present a paired liver–plasma proteomics approach to infer molecular pathophysiology and to explore the diagnostic and prognostic capability of plasma proteomics in 596 individuals (137 controls and 459 individuals with ALD), 360 of whom had biopsy-based histological assessment. We analyzed all plasma samples and 79 liver biopsies using a mass spectrometry (MS)-based proteomics workflow with short gradient times and an enhanced, data-independent acquisition scheme in only 3 weeks of measurement time. In plasma and liver biopsy tissues, metabolic functions were downregulated whereas fibrosis-associated signaling and immune responses were upregulated. Machine learning models identified proteomics biomarker panels that detected significant fibrosis (receiver operating characteristic–area under the curve (ROC–AUC), 0.92, accuracy, 0.82) and mild inflammation (ROC–AUC, 0.87, accuracy, 0.79) more accurately than existing clinical assays (DeLong’s test, P < 0.05). These biomarker panels were found to be accurate in prediction of future liver-related events and all-cause mortality, with a Harrell’s C-index of 0.90 and 0.79, respectively. An independent validation cohort reproduced the diagnostic model performance, laying the foundation for routine MS-based liver disease testing.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
For years, the use of ketamine as an anesthetic to patients suffering from acute brain injury has been debated because of its possible deleterious effects on the cerebral circulation and thus on the cerebral perfusion. Early studies suggested that ketamine could increase the intracranial pressure thus lowering the cerebral perfusion and hence reduce the oxygen supply to the injured brain. However, more recent studies are less conclusive and might even indicate that patients with acute brain injury could benefit from ketamine sedation. This systematic review summarizes the evidence regarding the use of ketamine in patients suffering from traumatic brain injury. Databases were searched for studies using ketamine in acute brain injury. Outcomes of interest were mortality, intracranial pressure, cerebral perfusion pressure, blood pressure, heart rate, spreading depolarizations, and neurological function. In total 11 studies were included. The overall level of evidence concerning the use of ketamine in brain injury is low. Only two studies found a small increase in intracranial pressure, while two small studies found decreased levels of intracranial pressure following ketamine administration. We found no evidence of harm during ketamine use in patients suffering from acute brain injury.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.