Higher neutrophil counts and neutrophil-to-lymphocyte ratio predict prognostic outcomes in patients after non-atrial fibrillation-caused ischemic stroke

Fang, Yueh‐Fu; Tong, Meng-Shen; Sung, Pei‐Hsun; Chen, Yung‐Lung; Chen, Chih‐Hung; Tsai, Nai‐Wen; Huang, Chih-Jen; Chang, Ya-Ting; Chen, Shu-Fang; Chang, Wen-Neng; Lu, Cheng-Hsien; Yip, Hon‐Kan

doi:10.1016/j.bj.2017.03.002

Cited by 56 publications

(66 citation statements)

References 34 publications

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“…Deciphering the exact mechanism of action of this antibody was beyond the scope of this research but proposes an interesting research question for investigators in this field. At least for now, the strong association of neutrophil/lymphocyte ratio in blood with severity of stroke in stroke patients is encouraging for our experimental observations (100)(101)(102)(103).…”

Section: Discussionsupporting

confidence: 56%

Neutrophil-mediated dynamic capillary stalls in ischemic penumbra: persistent traffic jams after reperfusion contribute to injury

Erdener

Tang

Kılıç

et al. 2019

Preprint

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the study objectives, designed and performed the experiments, acquired, processed and analyzed the data, wrote the manuscript. J.T. set up and optimized the OCT equipment, wrote acquisition codes and processing algorithms. K.K. designed surgical procedures and performed experiments. D.P set up and optimized the laser speckle imaging equipment, S.K wrote data analysis codes, analyzed data. A.C and J.G. set up and optimized two-photon microscope, prepared data analysis codes and performed the experiments. T.V. performed experiments, acquired and analyzed data. S.S. and C.B.S. contributed to study objectives and experimental design and critically evaluated the manuscript. D.A.B. supervised the project in overall, contributed to study objectives and experimental design, and critically evaluated the manuscript. AbstractEver since the introduction of thrombolysis and the subsequent expansion of endovascular treatments for acute ischemic stroke, it remains to be identified why the actual outcomes are less favorable despite recanalization. Here, by high spatio-temporal resolution imaging of capillary circulation in mice, we introduce the pathological phenomenon of dynamic flow stalls in cerebral capillaries, occurring persistently in the salvageable penumbra after recanalization. These stalls, which are distinct from permanent cellular plugs that can lead to no-flow, were temporarily and repetitively occurring in the capillary network, impairing the overall circulation like small focal traffic jams. In vivo microscopy in the ischemic penumbra revealed leukocytes traveling through capillary lumen or getting stuck, while red blood cell flow was being disturbed in the neighboring segments, within 3 hours after stroke onset. Stall dynamics could be modulated, by injection of an anti-Ly6G antibody specifically targeting neutrophils. By decreasing the number and duration of stalls, we were able to improve the blood flow in the penumbra within 2-24 hours after reperfusion, increase capillary oxygenation, decrease cellular damage and improve functional outcome. Thereby the dynamic microcirculatory stall phenomenon contributes to the ongoing penumbral injury and is a potential hyperacute stage mechanism adding on previous observations of detrimental effects of activated neutrophils in ischemic stroke. SignificanceThis work provides in vivo evidence that, even in perfused capillaries, abnormal capillary flow patterns in the form of dynamic stalls can contribute to ongoing tissue injury in the salvageable penumbra in very early hours of cerebral ischemia. These events resembling micro traffic jams in a complex road network, are mediated by passage of neutrophils through the microcirculation and persist despite recanalization of the occluded artery.

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Section: Discussionsupporting

confidence: 56%

Neutrophil-mediated dynamic capillary stalls in ischemic penumbra: persistent traffic jams after reperfusion contribute to injury

Erdener

Tang

Kılıç

et al. 2019

Preprint

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“…One of the mechanisms may be that the reduction in lymphocyte count represents an acute stress response in humans, and another may be that the relative reduction in lymphocytes is a marker of increased prestroke cortisol levels and sympathetic tone, which cause an increase in pro‐inflammatory factors, thereby aggravating ischemic injury (Acanfora et al, ; Ommen, Gibbons, Hodge, & Thomson, ; Park et al, ). Therefore, high NLR in peripheral blood predicts poor prognosis in patients with AIS (Fang et al, ; Hermann et al, ).…”

Section: Discussionmentioning

confidence: 99%

Neutrophil‐to‐lymphocyte ratio predicts hemorrhagic transformation in ischemic stroke: A meta‐analysis

Zhang

Xiao-dong

et al. 2019

Brain and Behavior

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Introduction The neutrophil‐to‐lymphocyte ratio (NLR) has been shown to be a marker associated with inflammation and is independently associated with the adverse clinical outcomes of symptomatic intracranial hemorrhage, cancer, and cardiovascular disease. Hemorrhagic transformation (HT) is a serious complication of ischemic cerebral infarction and can be intensified by therapeutic interventions for acute ischemic stroke (AIS). The purpose of our research was to explore the predictive effect of NLR for HT in patients with AIS and to determine the best predictive value. Methods PubMed, Web of Science, EMBASE, MEDLINE, Cochrane, and Google Scholar were searched. The primary endpoint was HT, and subgroup analysis was performed. Review Manager software version 5.3 was used to statistically analyze the outcomes. Results A total of seven studies including 3,726 patients met the inclusion criteria. The pooled odds ratio (OR) value of the high NLR that predicted HT in AIS patients was 1.53 (95% CI, 1.21–1.92; p = .0003). In addition, 1.10 (95% CI, 1.05–1.15; p < .0001) was the pooled OR of the high NLR associated with increased 3‐month mortality in patients with AIS. In the subgroup analysis with an NLR cutoff value of 7.5–11, the correlation between NLR above the cutoff value and the rate of HT in patients with AIS was statistically significant (OR, 7.93; 95% CI, 2.25–27.95; p = .001). Conclusion A high NLR can predict HT and 3‐month mortality in patients with AIS. Regardless of the country of origin and the sampling time, an NLR with a cutoff value of 7.5–11 was independently associated with HT in AIS patients.

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“…NLR reflects the immune status (lymphocytes) [26] and the degree of inflammatory infiltration (neutrophil) [26][27][28]. Recently, NLR was considered as a predictor for clinical outcomes in hemorrhagic [14,15,29] and ischemic stroke [17,20,30]. To our best knowledge, the present study is the first meta-analysis to evaluate the predictive value of NLR for the clinical outcomes in patients with ischemic stroke.…”

Section: Discussionmentioning

confidence: 84%

“…A total of 8 studies [4,[17][18][19][20][21][22][23] of 3855 patients were included and the study characteristics of were listed in Table 1. All studies (2 prospective and 6 retrospective) were published between 2013 and 2017 with mean age from 62 to 70 years.…”

Section: Study Characteristicsmentioning

confidence: 99%

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The prediction of neutrophil to lymphocyte ratio for outcomes in ischemic stroke

Ye¹,

Ai²,

Fang³

et al. 2017

Oncotarget

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Objective: Neutrophil to lymphocyte ratio (NLR) is a prognostic inflammatory biomarker in patients with cardiovascular disease and hemorrhagic stroke. This metaanalysis aims to evaluate the prognostic values of NLR in predicting clinical outcomes in patients with ischemic stroke.Methods: A literature search was performed using the databases PubMed, EMBASE, Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure. Two reviewers independently retrieved papers that met the inclusion criteria. Subgroup analyses were performed using in-hospital mortality, 90-day mortality and 90-day poor outcomes (mRS>2) as the outcome measures.Results: Eight studies with 3855 patients were included in the analysis. An elevated NLR was a strong predictor for in-hospital mortality (OR: 1.05; 95% CI: 1.03-1.07, p<0.001) and for 90-day poor outcomes (OR: 2.28; 95% CI: 1.39-3.73, p<0.001), but not for 90-day mortality (OR: 3.04; 95% CI: 0.74-12.55, p=0.12). After performing subgroup analysis, the NLR was found to predict 90-day mortality with a high (>5) cut-off values (OR: 6.69; 95% CI: 1.70-26.33, p=0.007). The lower cut-off values had no significance (OR: 2.17; 95% CI: 0.43-10.86, p=0.35).Conclusions: A high NLR was significantly associated with higher rates of inhospital mortality and 90-day poor outcome in patients with ischemic stroke, especially with a high mean NLR or high cut-off values. With a high cut-off value (>5), NLR could predict the 90-day mortality after ischemic stroke.

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Higher neutrophil counts and neutrophil-to-lymphocyte ratio predict prognostic outcomes in patients after non-atrial fibrillation-caused ischemic stroke

Cited by 56 publications

References 34 publications

Neutrophil-mediated dynamic capillary stalls in ischemic penumbra: persistent traffic jams after reperfusion contribute to injury

Neutrophil-mediated dynamic capillary stalls in ischemic penumbra: persistent traffic jams after reperfusion contribute to injury

Neutrophil‐to‐lymphocyte ratio predicts hemorrhagic transformation in ischemic stroke: A meta‐analysis

The prediction of neutrophil to lymphocyte ratio for outcomes in ischemic stroke

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