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Zhu Y, Li X, Lei X, Tang L, Wen D, Zeng B, Zhang X, Huang Z, Guo Z. The potential mechanism and clinical application value of remote ischemic conditioning in stroke. Neural Regen Res 2025; 20:1613-1627. [PMID: 38845225 PMCID: PMC11688546 DOI: 10.4103/nrr.nrr-d-23-01800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 01/30/2024] [Accepted: 03/19/2024] [Indexed: 08/07/2024] Open
Abstract
Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.
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Affiliation(s)
- Yajun Zhu
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiaoguo Li
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xingwei Lei
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Liuyang Tang
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Daochen Wen
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Bo Zeng
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiaofeng Zhang
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zichao Huang
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zongduo Guo
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Duan RX, Liu L, Wang Y, Wu WM. Prognostic value of combined detection of alpha-fetoprotein, plasma prothrombin activity, and serum prealbumin in acute-on-chronic liver failure. World J Gastrointest Surg 2025; 17:99531. [DOI: 10.4240/wjgs.v17.i2.99531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 11/11/2024] [Accepted: 12/19/2024] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF) is a liver disease based on chronic liver disease, which is significantly influenced by clinical treatment regimen and disease status, and despite the existence of multiple prognostic assessment indicators for ACLF, the overall sensitivity and accuracy are relatively low.
AIM To investigate the prognostic value of the combined detection of alpha-fetoprotein (AFP), plasma prothrombin activity (PTA), and serum prealbumin (PA) in ACLF.
METHODS This retrospective study included 87 patients with ACLF admitted from February 2021 to February 2023 and categorized them into the survival (n = 47) and death (n = 40) groups according to their clinical outcomes 3 months posttreatment. All the participants underwent AFP, PTA, and PA level measurements upon admission. Baseline data, as well as AFP, PTA, and PA levels, were comparatively analyzed. Pearson correlation coefficients were utilized to analyze the correlations of AFP, PTA, and PA with different survival outcomes in patients with ACLF. Receiver operating characteristic (ROC) curves and areas under the curves were used to evaluate the predictive value of AFP, PTA, and PA for ACLF prognosis.
RESULTS AFP, PTA, and PA levels were markedly decreased in the death group than in the survival group (P < 0.05). Pearson analysis indicated a positive association of the AFP, PTA, and PA levels with the survival of patients with ACLF (P < 0.05). ROC curve analysis determined the sensitivity and specificity of the combined diagnosis at 91.24% and 100.00%, respectively, both of which were notably increased compared to the single-index diagnosis. The ROC of their combined diagnosis was 0.989, significantly surpassing 0.907, 0.849, and 0.853 of AFP, PTA, and PA, respectively. No statistically significant variance was determined in the sensitivity and specificity of the combined diagnosis vs the single detection (P > 0.05).
CONCLUSION The combined detection of AFP, PTA, and PA levels demonstrates favorable diagnostic value for the short-term prognosis of patients with ACLF, featuring high sensitivity and specificity.
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Affiliation(s)
- Rui-Xian Duan
- Department of Infectious Diseases, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan 030032, Shanxi Province, China
| | - Ling Liu
- Department of Pulmonary Diseases, Shanxi Provincial Integrated TCM and WM Hospital, Taiyuan 030013, Shanxi Province, China
| | - Yan Wang
- Department of Infectious Diseases, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan 030032, Shanxi Province, China
| | - Wen-Ming Wu
- Clinical Laboratory, Shanxi Provincial People’s Hospital, Taiyuan 030023, Shanxi Province, China
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Liu QY, Cui Y, Li W, Qiu J, Nguyen TN, Chen HS. Effect of remote ischemic preconditioning on cerebral circulation time in severe carotid artery stenosis: Results from the RIC-CCT trial. Cell Rep Med 2024; 5:101796. [PMID: 39471820 PMCID: PMC11604480 DOI: 10.1016/j.xcrm.2024.101796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 08/21/2024] [Accepted: 09/27/2024] [Indexed: 11/01/2024]
Abstract
In patients with severe internal carotid artery stenosis (sICAS), cerebral circulation time (CCT) is associated with cerebral hyperperfusion syndrome. This study aims to investigate the effect of remote ischemic preconditioning (RIC) on CCT in patients with sICAS. Patients are randomly assigned to the RIC group (RIC twice daily, for 2-4 days before carotid artery stenting [CAS] as an adjunct to standard medical therapy) and the control group. The results show that RIC produces a significant decrease in CCT of the stenosis side (sCCT) from baseline to pre-CAS, and the occurrence of contrast staining on brain computed tomography (CT) is lower in RIC versus control group after CAS. In addition, significant changes in some serum biomarkers suggest that anti-neuroinflammation, anti-oxidative stress, protecting endothelial injury, and improving cerebral autoregulation may be associated with the effect of RIC. These findings provide supporting evidence that RIC can modulate cerebral circulation in patients with sICAS. This study was registered at ClinicalTrials.gov (NCT05451030).
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Affiliation(s)
- Quan-Ying Liu
- Department of Neurology, General Hospital of Northern Theater Command, Shenyang 110016, China
| | - Yu Cui
- Department of Neurology, General Hospital of Northern Theater Command, Shenyang 110016, China
| | - Wei Li
- Department of Neurology, General Hospital of Northern Theater Command, Shenyang 110016, China
| | - Jing Qiu
- Department of Neurology, General Hospital of Northern Theater Command, Shenyang 110016, China
| | - Thanh N Nguyen
- Department of Neurology, Radiology, Boston Medical Center, Boston, MA, USA
| | - Hui-Sheng Chen
- Department of Neurology, General Hospital of Northern Theater Command, Shenyang 110016, China.
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Jiang B, Wang X, Ma J, Fayyaz A, Wang L, Qin P, Ding Y, Ji X, Li S. Remote ischemic conditioning after stroke: Research progress in clinical study. CNS Neurosci Ther 2024; 30:e14507. [PMID: 37927203 PMCID: PMC11017418 DOI: 10.1111/cns.14507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 09/14/2023] [Accepted: 10/06/2023] [Indexed: 11/07/2023] Open
Abstract
BACKGROUND AND PURPOSE Stroke is a leading cause of global morbidity and mortality, indicating the necessity and urgency of effective prevention and treatment. Remote ischemic conditioning (RIC) is a convenient, simple, non-intrusive, and effective method that can be easily added to the treatment regime of stroke patients. Animal experiments and clinical trials have proved the neuroprotective effects of RIC on brain injury including (examples of neuroprotective effects). This neuroprotection is achieved by raising brain tolerance to ischemia, increasing local cerebral blood perfusion, promoting collateral circulations, neural regeneration, and reducing the incidence of hematomas in brain tissue. This current paper will summarize the studies within the last 2 years for the comprehensive understanding of the use of RIC in the treatment of stroke. METHODS This paper summarizes the clinical research progress of RIC on stroke (ischemic stroke and hemorrhagic stroke (HS)). This paper is a systematic review of research published on registered clinical trials using RIC in stroke from inception through November 2022. Four major databases (PUBMED, WEB OF SCIENCE, EMBASE, and ClinicalTrials.gov) were searched. RESULTS Forty-eight studies were identified meeting our criteria. Of these studies, 14 were in patients with acute ischemic stroke with onset times ranging from 6 h to 14 days, seven were in patients with intravenous thrombolysis or endovascular thrombectomy, 10 were in patients with intracranial atherosclerotic stenosis, six on patients with vascular cognitive impairment, three on patients with moyamoya disease, and eight on patients with HS. Of the 48 studies, 42 were completed and six are ongoing. CONCLUSIONS RIC is safe, feasible, and effective in the treatment of stroke. Large-scale research is still required to explore the optimal treatment options and mechanisms of RIC in the future to develop a breakthrough in stroke prevention and treatment.
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Affiliation(s)
- Bin Jiang
- Department of NeurologyShenzhen Qianhai Shekou Free Trade Zone HospitalShenzhenChina
| | - Xiaojie Wang
- Department of NeurologyShenzhen Qianhai Shekou Free Trade Zone HospitalShenzhenChina
| | - Jianping Ma
- Department of NeurologyShenzhen Qianhai Shekou Free Trade Zone HospitalShenzhenChina
| | - Aminah Fayyaz
- Department of NeurosurgeryWayne State University School of MedicineDetroitMichiganUSA
| | - Li Wang
- Department of NeurologyShenzhen Qianhai Shekou Free Trade Zone HospitalShenzhenChina
| | - Pei Qin
- Department of NeurologyShenzhen Qianhai Shekou Free Trade Zone HospitalShenzhenChina
| | - Yuchuan Ding
- Department of NeurosurgeryWayne State University School of MedicineDetroitMichiganUSA
| | - Xunming Ji
- Department of Neurology, Xuanwu HospitalCapital Medical UniversityBeijingChina
- Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain DisordersCapital Medical UniversityBeijingChina
| | - Sijie Li
- Department of Emergency, Xuanwu HospitalCapital Medical UniversityBeijingChina
- Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Xuanwu HospitalCapital Medical UniversityBeijingChina
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Keevil H, Phillips BE, England TJ. Remote ischemic conditioning for stroke: A critical systematic review. Int J Stroke 2024; 19:271-279. [PMID: 37466245 PMCID: PMC10903142 DOI: 10.1177/17474930231191082] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Accepted: 07/10/2023] [Indexed: 07/20/2023]
Abstract
Remote ischemic conditioning (RIC) is the application of brief periods of ischemia to an organ or tissue with the aim of inducing protection from ischemia in a distant organ. It was first developed as a cardioprotective strategy but has been increasingly investigated as a neuroprotective intervention. The mechanisms by which RIC achieves neuroprotection are incompletely understood. Preclinical studies focus on the hypothesis that RIC can protect the brain from ischemia reperfusion (IR) injury following the restoration of blood flow after occlusion of a large cerebral artery. However, increasingly, a role of chronic RIC (CRIC) is being investigated as a means of promoting recovery following an ischemic insult to the brain. The recent publication of two large, randomized control trials has provided promise that RIC could improve functional outcomes after acute ischemic stroke, and that there may be a role for CRIC in the prevention of recurrent stroke. Although less developed, there is also proof-of-concept to suggest that RIC may be used to reduce vasospasm after subarachnoid hemorrhage or improve cognitive outcomes in vascular dementia. As a cheap, well-tolerated and almost universally applicable intervention, the motivation for investigating possible benefit of RIC in patients with cerebrovascular disease is great. In this review, we shall review the current evidence for RIC as applied to cerebrovascular disease.
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Affiliation(s)
- Harry Keevil
- Stroke Trials Unit, Division of Mental Health and Clinical Neuroscience, University of Nottingham, Nottingham, UK
- Medical Research Council Versus Arthritis Centre for Musculoskeletal Ageing Research, and NIHR Nottingham Biomedical Research Centre, Division of Injury, Recovery & Inflammation Sciences, University of Nottingham, Nottingham, UK
| | - Bethan E Phillips
- Medical Research Council Versus Arthritis Centre for Musculoskeletal Ageing Research, and NIHR Nottingham Biomedical Research Centre, Division of Injury, Recovery & Inflammation Sciences, University of Nottingham, Nottingham, UK
| | - Timothy J England
- Stroke Trials Unit, Division of Mental Health and Clinical Neuroscience, University of Nottingham, Nottingham, UK
- Department of Stroke, University Hospitals of Derby and Burton, Derby, UK
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Tjerkstra MA, Wolfs AE, Verbaan D, Vandertop WP, Horn J, Müller MCA, Juffermans NP. A Systematic Review of Viscoelastic Testing in Patients with Subarachnoid Hemorrhage. World Neurosurg 2023; 175:102-112.e5. [PMID: 37004882 DOI: 10.1016/j.wneu.2023.03.108] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 03/26/2023] [Indexed: 04/03/2023]
Abstract
OBJECTIVE Bleeding and thromboembolic complications frequently occur after subarachnoid hemorrhage (SAH) and substantially contribute to poor outcome. Viscoelastic testing could be used for detection of coagulopathies after SAH. This review summarizes literature on the usefulness of viscoelastic testing to detect coagulopathy in patients with SAH and explores whether viscoelastic parameters are associated with SAH-related complications and clinical outcome. METHODS PubMed, Embase, and Google Scholar were systematically searched on August 18, 2022. Two authors independently selected studies that reported viscoelastic testing in patients with SAH and assessed the quality of studies using the Newcastle-Ottawa Scale or a previously reported framework for quality assessment. Data were meta-analyzed if methodologically possible. RESULTS The search yielded 19 studies (1160 patients with SAH). Pooling of data including all relevant studies was not possible for any of the outcome measurements because of methodological differences. Thirteen of 19 studies evaluated the association of coagulation profiles and SAH, of which 11 studies showed a hypercoagulable profile. Rebleeding was associated with platelet dysfunction, deep venous thrombosis was associated with faster clot initiation, and both delayed cerebral ischemia and poor outcome were associated with increased clot strength. CONCLUSIONS This explorative review shows that patients with SAH frequently have a hypercoagulable profile. Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) parameters are associated with rebleeding, delayed cerebral ischemia, deep venous thrombosis, and poor clinical outcome after SAH; however, more research on the subject is needed. Future studies should focus on determining the optimal time frame and cutoff values for TEG or ROTEM to predict these complications.
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Affiliation(s)
- Maud A Tjerkstra
- Amsterdam UMC, University of Amsterdam, Department of Neurosurgery, Amsterdam Neuroscience, Amsterdam, the Netherlands.
| | - Anne E Wolfs
- Amsterdam UMC, University of Amsterdam, Department of Neurosurgery, Amsterdam Neuroscience, Amsterdam, the Netherlands
| | - Dagmar Verbaan
- Amsterdam UMC, University of Amsterdam, Department of Neurosurgery, Amsterdam Neuroscience, Amsterdam, the Netherlands
| | - W Peter Vandertop
- Amsterdam UMC, University of Amsterdam, Department of Neurosurgery, Amsterdam Neuroscience, Amsterdam, the Netherlands
| | - Janneke Horn
- Amsterdam UMC, University of Amsterdam, Department of Intensive Care, Amsterdam Neuroscience, Amsterdam, the Netherlands
| | - Marcella C A Müller
- Amsterdam UMC, University of Amsterdam, Department of Intensive Care, Amsterdam Neuroscience, Amsterdam, the Netherlands
| | - Nicole P Juffermans
- Amsterdam UMC, University of Amsterdam, Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam Neuroscience, Amsterdam, the Netherlands; Department of Intensive Care, OLVG Hospital, Amsterdam, the Netherlands
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Hvas CL, Hvas AM. Viscoelastic Testing in the Clinical Management of Subarachnoid Hemorrhage and Intracerebral Hemorrhage. Semin Thromb Hemost 2022; 48:828-841. [PMID: 36100233 DOI: 10.1055/s-0042-1756191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
Subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH) are both debilitating and life-threatening incidents calling for immediate action and treatment. This review focuses on the applicability of viscoelastic testing (rotational thromboelastometry or thromboelastography [TEG]) in the management of SAH and ICH. A systematic literature search was performed in PubMed and EMBASE. Studies including patients with SAH or ICH, in which viscoelastic testing was performed, were identified. In total, 24 studies were included for analysis, and further subdivided into studies on SAH patients investigated prior to stenting or coiling (n = 12), ICH patients (n = 8) and studies testing patients undergoing stenting or coiling, or ischemic stroke patients undergoing thrombolysis or thrombectomy and developing ICH as a complication (n = 5). SAH patients had increased clot firmness, and this was associated with a higher degree of early brain injury and higher Hunt-Hess score. SAH patients with delayed cerebral ischemia had higher clot firmness than patients not developing delayed cerebral ischemia. ICH patients showed accelerated clot formation and increased clot firmness in comparison to healthy controls. Patients with hematoma expansion had longer clot initiation and lower platelet aggregation than patients with no hematoma expansion. During stent procedures for SAH, adjustment of antiplatelet therapy according to TEG platelet mapping did not change prevalence of major bleeding, thromboembolic events, or functional outcome. Viscoelastic testing prior to thrombolysis showed conflicting results in predicting ICH as complication. In conclusion, viscoelastic testing suggests hypercoagulation following SAH and ICH. Further investigation of the predictive value of increased clot firmness in SAH seems relevant. In ICH, the prediction of hematoma expansion and ICH as a complication to thrombolysis might be clinically relevant.
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Affiliation(s)
- Christine Lodberg Hvas
- Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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Krag AE, Blauenfeldt RA. Fibrinolysis and Remote Ischemic Conditioning: Mechanisms and Treatment Perspectives in Stroke. Semin Thromb Hemost 2021; 47:610-620. [PMID: 33878783 DOI: 10.1055/s-0041-1725095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Stroke is a leading cause of death and disability. Intravenous thrombolysis and mechanical thrombectomy have greatly improved outcomes in acute ischemic stroke (AIS). However, only a minority of patients receive reperfusion therapies, highlighting the need for novel neuroprotective therapies. Remote ischemic conditioning (RIC), consisting of brief, intermittent extremity occlusion and reperfusion induced with an inflatable cuff, is a potential neuroprotective therapy in acute stroke. The objective of this narrative review is to describe the effect of RIC on endogenous fibrinolysis and, from this perspective, investigate the potential of RIC in the prevention and treatment of stroke. A systematic literature search was performed in PubMed, and human studies in English were included. Seven studies had investigated the effect of RIC on fibrinolysis in humans. Long-term daily administration of RIC increased endogenous fibrinolysis, whereas a single RIC treatment did not acutely influence endogenous fibrinolysis. Fifteen studies had investigated the effect of RIC as a neuroprotective therapy in the prevention and treatment of stroke. Long-term RIC administration proved effective in reducing new cerebral vascular lesions in patients with established cerebrovascular disease. In patients with acute stroke, RIC was safe and feasible, though its clinical efficacy as a neuroprotectant is yet unproven. In conclusion, a single RIC treatment does not affect fibrinolysis in the acute phase, whereas long-term RIC administration may increase endogenous fibrinolysis. Increased endogenous fibrinolysis is unlikely to be the mediator of the acute neuroprotective effect of RIC in stroke patients, whereas it may partly explain the reduced stroke recurrence associated with long-term RIC treatment.
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Affiliation(s)
- Andreas Engel Krag
- Thrombosis and Hemostasis Research Unit, Aarhus University Hospital, Aarhus, Denmark
| | - Rolf Ankerlund Blauenfeldt
- Department of Neurology, Danish Stroke Center, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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