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      Monomeric C-Reactive Protein and Cerebral Hemorrhage: From Bench to Bedside

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          Abstract

          C-reactive protein (CRP) is an important mediator and a hallmark of the acute-phase response to inflammation. High-sensitivity assays that accurately measure levels of CRP have been recommended for use in risk assessment in ischemic stroke patients. Elevation of CRP during the acute-phase response in intracerebral hemorrhage (ICH) is also associated with the outcomes such as death and vascular complications. However, no association has been found with the increased risk of ICH. The aim of this review is to synthesize the published literature on the associations of CRP with acute ICH both as a risk biomarker and predictor of short- and long-term outcomes as well as its role as a pathogenic determinant. We believe before any clinical utility, a critical appraisal of the strengths and deficiencies of the accumulated evidence is required both to evaluate the current state of knowledge and to improve the design of future clinical studies.

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          Most cited references74

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          Human C-reactive protein: expression, structure, and function

          Molecular Immunology, 38(2-3), 189-197
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            Risk factors for subarachnoid hemorrhage: an updated systematic review of epidemiological studies.

            After a 1996 review from our group on risk factors for subarachnoid hemorrhage (SAH), much new information has become available. This article provides an updated overview of risk factors for SAH. An overview of all longitudinal and case-control studies of risk factors for SAH published in English from 1966 through March 2005. We calculated pooled relative risks (RRs) for longitudinal studies and odds ratios (ORs) for case-control studies, both with corresponding 95% CIs. We included 14 longitudinal (5 new) and 23 (12 new) case-control studies. Overall, the studies included 3936 patients with SAH (892 cases in 14 longitudinal studies and 3044 cases in 23 case-control studies) for analysis. Statistically significant risk factors in longitudinal and case-control studies were current smoking (RR, 2.2 [1.3 to 3.6]; OR, 3.1 [2.7 to 3.5]), hypertension (RR, 2.5 [2.0 to 3.1]; OR, 2.6 [2.0 to 3.1]), and excessive alcohol intake (RR, 2.1 [1.5 to 2.8]; OR, 1.5 [1.3 to 1.8]). Nonwhite ethnicity was a less robust risk factor (RR, 1.8 [0.8 to 4.2]; OR, 3.4 [1.0 to 11.9]). Oral contraceptives did not affect the risk (RR, 5.4 [0.7 to 43.5]; OR, 0.8 [0.5 to 1.3]). Risk reductions were found for hormone replacement therapy (RR, 0.6 [0.2 to 1.5]; OR, 0.6 [0.4 to 0.8]), hypercholesterolemia (RR, 0.8 [0.6 to 1.2]; OR, 0.6 [0.4 to 0.9]), and diabetes (RR, 0.3 [0 to 2.2]; OR, 0.7 [0.5 to 0.8]). Data were inconsistent for lean body mass index (RR, 0.3 [0.2 to 0.4]; OR, 1.4 [1.0 to 2.0]) and rigorous exercise (RR, 0.5 [0.3 to 1.0]; OR, 1.2 [1.0 to 1.6]). In the studies included in the review, no other risk factors were available for the meta-analysis. Smoking, hypertension, and excessive alcohol remain the most important risk factors for SAH. The seemingly protective effects of white ethnicity compared to nonwhite ethnicity, hormone replacement therapy, hypercholesterolemia, and diabetes in the etiology of SAH are uncertain.
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              Subarachnoid haemorrhage: diagnosis, causes and management

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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                11 September 2018
                2018
                : 9
                : 1921
                Affiliations
                [1] 1Department of Neurology and Stroke Unit, San Camillo de' Lellis General Hospital , Rieti, Italy
                [2] 2Healthcare Science, Manchester Metropolitan University , Manchester, United Kingdom
                [3] 3Department of Neurology, University of Medicine Essen , Essen, Germany
                [4] 4Center of Clinical and Experimental Medicine, University of Medicine and Pharmacy , Craiova, Romania
                [5] 5Department of Human Genetics, Punjabi University , Patiala, India
                [6] 6Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University , Ancona, Italy
                [7] 7Department of Neurology, University of Minnesota , Minneapolis, MN, United States
                [8] 8Department of Neurosurgery, University of Minnesota , Minneapolis, MN, United States
                Author notes

                Edited by: Fulvio D'Acquisto, University of Roehampton, United Kingdom

                Reviewed by: Alejandra Pera, Universidad de Córdoba, Spain; Luz Pamela Blanco, National Institutes of Health (NIH), United States

                *Correspondence: Mario Di Napoli mariodinapoli@ 123456katamail.com

                This article was submitted to Inflammation, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2018.01921
                6141664
                30254628
                9a452b92-0b74-4a39-a917-9dccc52e7890
                Copyright © 2018 Di Napoli, Slevin, Popa-Wagner, Singh, Lattanzi and Divani.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 02 March 2018
                : 03 August 2018
                Page count
                Figures: 2, Tables: 1, Equations: 0, References: 85, Pages: 11, Words: 8480
                Categories
                Immunology
                Mini Review

                Immunology
                crp,inflammation,stroke,intracerebral hemorrhage,sap,outcomes,risk assessment,biomarkers
                Immunology
                crp, inflammation, stroke, intracerebral hemorrhage, sap, outcomes, risk assessment, biomarkers

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