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      Proteomic profile and predictive markers of outcome in patients with subarachnoid hemorrhage

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          Abstract

          Background

          The molecular mechanisms underlying development of posthemorrhagic hydrocephalus (PHH) following subarachnoid hemorrhage (SAH) remain incompletely understood. Consequently, treatment strategies tailored towards the individual patient remain limited. This study aimed to identify proteomic cerebrospinal fluid (CSF) biomarkers capable of predicting shunt dependency and functional outcome in patients with SAH in order to improve informed clinical decision making.

          Methods

          Ventricular CSF samples were collected twice from 23 patients with SAH who required external ventricular drain (EVD) insertion (12 patients with successful EVD weaning, 11 patients in need of permanent CSF shunting due to development of PHH). The paired CSF samples were collected acutely after ictus and later upon EVD removal. Cisternal CSF samples were collected from 10 healthy control subjects undergoing vascular clipping of an unruptured aneurysm. All CSF samples were subjected to mass spectrometry-based proteomics analysis. Proteomic biomarkers were quantified using area under the curve (AUC) estimates from a receiver operating curve (ROC).

          Results

          CSF from patients with SAH displayed a distinct proteomic profile in comparison to that of healthy control subjects. The CSF collected acutely after ictus from patients with SAH was moreover distinct from that collected weeks later but appeared similar in the weaned and shunted patient groups. Sixteen unique proteins were identified as potential predictors of shunt dependency, while three proteins were identified as potential predictors of functional outcome assessed six months after ictus with the modified Rankin Scale.

          Conclusions

          We here identified several potential proteomic biomarkers in CSF from patients with SAH capable of predicting (i) shunt dependency and thus development of PHH and (ii) the functional outcome assessed six months after ictus. These proteomic biomarkers may have the potential to aid clinical decision making by predicting shunt dependency and functional outcome following SAH.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12014-024-09493-6.

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          Most cited references62

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            Minimal, encapsulated proteomic-sample processing applied to copy-number estimation in eukaryotic cells.

            Mass spectrometry (MS)-based proteomics typically employs multistep sample-preparation workflows that are subject to sample contamination and loss. We report an in-StageTip method for performing sample processing, from cell lysis through elution of purified peptides, in a single, enclosed volume. This robust and scalable method largely eliminates contamination or loss. Peptides can be eluted in several fractions or in one step for single-run proteome analysis. In one day, we obtained the largest proteome coverage to date for budding and fission yeast, and found that protein copy numbers in these cells were highly correlated (R(2) = 0.78). Applying the in-StageTip method to quadruplicate measurements of a human cell line, we obtained copy-number estimates for 9,667 human proteins and observed excellent quantitative reproducibility between replicates (R(2) = 0.97). The in-StageTip method is straightforward and generally applicable in biological or clinical applications.
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              Evolution of the Modified Rankin Scale and Its Use in Future Stroke Trials.

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                Author and article information

                Contributors
                macaulay@sund.ku.dk
                Marianne.Juhler@regionH.dk
                Journal
                Clin Proteomics
                Clin Proteomics
                Clinical Proteomics
                BioMed Central (London )
                1542-6416
                1559-0275
                23 July 2024
                23 July 2024
                2024
                : 21
                : 51
                Affiliations
                [1 ]GRID grid.475435.4, Department of Neurosurgery, the Neuroscience Centre, , Copenhagen University Hospital – Rigshospitalet, ; Copenhagen, Denmark
                [2 ]Department of Neuroscience, University of Copenhagen, ( https://ror.org/035b05819) Copenhagen, Denmark
                [3 ]GRID grid.475435.4, Department of Neuroanaesthesiology, the Neuroscience Centre, , Copenhagen University Hospital – Rigshospitalet, ; Copenhagen, Denmark
                [4 ]GRID grid.512923.e, ISNI 0000 0004 7402 8188, Department of Anaesthesiology, , Zealand University Hospital, ; Køge, Denmark
                [5 ]NNF Center for Protein Research, University of Copenhagen, ( https://ror.org/035b05819) Copenhagen, Denmark
                [6 ]GRID grid.411702.1, ISNI 0000 0000 9350 8874, Department of Clinical Biochemistry, , Copenhagen University Hospital – Bispebjerg and Frederiksberg Hospital, ; Copenhagen, Denmark
                [7 ]Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, ( https://ror.org/035b05819) Copenhagen, Denmark
                Author information
                http://orcid.org/0000-0002-6965-0939
                http://orcid.org/0000-0002-6384-9840
                http://orcid.org/0000-0003-0981-0723
                http://orcid.org/0009-0005-6837-9170
                http://orcid.org/0000-0003-1896-7749
                http://orcid.org/0000-0002-7800-6600
                http://orcid.org/0000-0003-2652-7495
                Article
                9493
                10.1186/s12014-024-09493-6
                11267790
                39044147
                e18aa4ad-12b2-4f59-a9e4-4a502f92838f
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 28 November 2023
                : 31 May 2024
                Funding
                Funded by: Copenhagen University
                Categories
                Research
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2024

                Molecular medicine
                subarachnoid hemorrhage,posthemorrhagic hydrocephalus,cerebrospinal fluid,biomarkers,mass spectrometry,proteomics

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