Neutrophils are readily activated immune cells after ischemic stroke in mice and patients. Still, the impact of gut microbiota on neutrophil activation and its influence on inflammatory brain injury remain undefined. We report that natural microbiota colonization of germ-free (GF) mice induces substantial neutrophil activation and deteriorates stroke pathology. The colonized Ex-GF stroke mice had considerably larger infarct sizes and higher sensorimotor deficits than GF littermates. Furthermore, employing an antibiotic-based mouse model of microbiota deficiency, we demonstrate that gut microbiota depletion induces a juvenile neutrophil phenotype characterized by the upregulation of resting state surface receptors, reduced inflammatory proteins, and levels of circulating NETs. This disarming of neutrophil responses was associated with decreased expression of brain inflammatory genes, vascular thrombus formation, reduced infarct size, and alleviated behavioral deficits. We conclude that gut microbes strongly influence neutrophil activation after stroke and thus directly contribute to stroke severity.

Neutrophils are the most abundant leukocytes in humans and are indispensable for innate immunity. They are short-lived, terminally differentiated cells. However, mounting evidence indicates that neutrophils are heterogeneous in health and disease: they are young or aged in a steady state, while their heterogeneity becomes more diverse in disease conditions, such as cancer, sepsis, and thromboinflammation. Although the presence of distinct neutrophil subsets is well recognized, it is not fully understood how neutrophils have functional and phenotypic heterogeneity and what mechanisms control it. This review will focus on our current understanding of the molecular basis for neutrophil heterogeneity in pathophysiological conditions. In addition, we will discuss the possibility of targeting a specific subset of neutrophils to attenuate inflammation and tissue damage without compromising innate immune responses.

The neutrophil percentage-to-albumin ratio (NPAR) is connected with all-cause mortality and stroke-related pneumonia. The purpose of this study was to assess the diagnostic efficacy of NPAR in predicting functional outcomes at 90 days after endovascular thrombectomy (EVT).

We retrospective analyzed consecutive patients who underwent EVT at Nanjing First Hospital from October 2019 to June 2024. NPAR was defined as the percentage of neutrophils divided by the albumin levels. An unfavorable outcome was indicated by a modified Rankin Scale score of 3-6 at 90 days. Multivariable logistic regression models were utilized to investigate the association between NPAR and functional outcomes after EVT treatment.

A total of 713 patients (mean age, 70.5 ± 11.9 years; 430 males) were finally enrolled for analysis. Among these, 357 (50.1%) patients exhibited unfavorable outcomes at 90 days. Multivariate regression analysis indicated that elevated NPAR levels at admission were independently associated with poor outcome (adjusted odds ratio: 6.921; 95% confidence interval, 4.216-11.363; P=0.001) in ischemic stroke patients undergoing EVT. Furthermore, the restricted cubic spline observed a positive and nonlinear association between the NPAR and poor outcome at 90 days (P for linearity=0.001).

This study indicated that higher NPAR levels were associated an increased risk of poor outcome at 90 days in patients treated with EVT, suggesting that NPAR could serve as a viable prognostic biomarker for ischemic stroke after EVT.

Ischemic stroke caused by cerebrovascular embolism is an age-related disease with high rates of disability and mortality. Although the mechanisms of immune and inflammatory development after stroke have been of great interest, most studies have neglected the critical and unavoidable factor of age. As the global aging trend intensifies, the number of stroke patients is constantly increasing, emphasizing the urgency of finding effective measures to address the needs of elderly stroke patients. The concept of "immunosenescence" appears to explain the worse stroke outcomes in older individuals. Immune remodeling due to aging involves dynamic changes at all levels of the immune system, and the overall consequences of central (brain-resident) and peripheral (non-brain-resident) immune cells in stroke vary according to the age of the individual. Lastly, the review outlines recent strategies aimed at immunosenescence to improve stroke prognosis.

Medial medullary infarction (MMI) is a rare type of posterior circulation stroke for which accurate prognostication remains a challenge because of the limited predictive ability of the current models. Blood-derived biomarkers may provide valuable insights that extend beyond established prognostic factors. The aim of this study was to identify rapid and accessible biomarkers for predicting the early progression of MMI.

Seventy patients with MMI and 83 sex- and age-matched healthy controls (HCs) were recruited for this study. Among them, 20 patients were allocated to the early progression cohort, and 50 patients were assigned to the nonprogression cohort. The laboratory blood indices were subsequently compared across these different cohorts. Receiver operating characteristic (ROC) curves were used to evaluate the predictive values of blood-derived indicators.

The white blood cell (WBC) count, neutrophil count, monocyte count, low-density lipoprotein cholesterol (LDL-C) level, total cholesterol (TC) concentration, WBC-to-high-density lipoprotein cholesterol (HDL-C) ratio (WHR), neutrophil-to-HDL-C ratio (NHR), monocyte-to-HDL-C ratio (MHR), monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were significantly greater in patients with MMI than in HCs (p < 0.05). The WBC count, neutrophil count, monocyte count, WHR, NHR, MHR, MLR, NLR and PLR were markedly higher in MMI patients with progression than in MMI patients without progression (p < 0.05). ROC curve analysis revealed that the WBC count, neutrophil count, monocyte count, MLR, NLR, PLR, NHR, and WHR were significant predictors of early progression. However, among these factors, the WBC count (AUC = 0.854, p < 0.001), neutrophil count (AUC = 0.878, p < 0.001), NLR (AUC = 0.861, p < 0.001), and NHR (AUC = 0.848, p < 0.001) had the highest levels of accuracy for predicting early progression in patients with MMI.

The efficacy of the WBC count, neutrophil count, NLR and NHR is superior in predicting progression in patients with MMI. The current findings suggest that these indicators may serve as reliable, cost-effective, and innovative prognostic markers for MMI.

Intravenous administration of recombinant tissue plasminogen activator (rt-PA) within 4.5 h of symptom onset is a standard treatment for acute ischemic stroke (AIS). However, certain patients continue to develop unfavorable outcomes despite timely rt-PA therapy. Identifying those at high risk is essential for developing individualized care plans and establishing appropriate follow-up.

This retrospective study included AIS patients treated with intravenous rt-PA at 0.9 mg/kg at our center. Outcomes at three months were evaluated using the modified Rankin Scale (mRS). Patients with mRS scores ≤2 were considered to have favorable outcomes, and those with scores >2 were considered to have poor outcomes. Univariable analysis and stepwise logistic regression were used to identify independent predictors of poor prognosis, and a nomogram was subsequently developed. The model's discriminative power was assessed with area under the receiver operating characteristic curves (AUC-ROC), and its calibration was examined using calibration plots. Decision curves and clinical impact curves were applied to determine clinical utility.

Among 392 enrolled patients, 77 had poor outcomes three months after rt-PA therapy. Fibrinogen (Fg), baseline NIHSS, and a history of hypertension emerged as independent predictors of poor prognosis. The nomogram achieved an AUC of 0.948 (95% CI [0.910-0.985]), with sensitivity of 0.900 and specificity of 0.916 in the training dataset, and an AUC of 0.959 (95% CI [0.907-1.000]), with sensitivity of 0.943 and specificity of 0.947 in the validation dataset. Calibration plots demonstrated close agreement between predicted and observed probabilities, and decision curves indicated a wide range of net benefit threshold probabilities.

This nomogram, incorporating baseline NIHSS, Fg, and a history of hypertension, accurately predicts poor three-month outcomes in AIS patients treated with intravenous rt-PA. Its ease of use may facilitate early risk stratification and assist clinicians in formulating more targeted management strategies and follow-up protocols for patients likely to experience unfavorable outcomes.

Recent studies have shown that the neutrophil-to-lymphocyte ratio (NLR) can predict short-term and long-term outcomes in acute ischemic stroke (AIS) patients. However, the relationship of the variation of NLR (ΔNLR) with hemorrhage transformation (HT) and early neurological improvement (ENI) after intravenous thrombolysis (IVT) remains unclear. This study aimed to investigate the impact of ΔNLR on HT and ENI at 24 h post-IVT and its association with different TOAST classifications. AIS patients undergoing IVT between October 2021 and October 2023 were enrolled and classified by TOAST criteria. Patients were grouped based on the presence or absence of HT and ENI. Our study demonstrated that both HT and ENI were associated with ΔNLR, which was an independent influencing factor for HT and ENI following IVT. Specifically, the ΔNLR in the small artery occlusion (SAO) group was higher than that in the minor stroke of large artery atherosclerosis (LAA) subtype. Thus, ΔNLR may serve as a useful biomarker to assist in diagnosis and monitor the outcomes of thrombolytic therapy in AIS patients.

Hyperperfusion-induced cerebral hemorrhage (HICH) is a rare but severe complication in patients with carotid stenosis undergoing stent placement for which predictive models are lacking. Our objective was to develop a nomogram to predict such risk.

We included a total of 1226 patients with carotid stenosis who underwent stenting between June 2015 and December 2022 from three medical centers, divided into a development cohort of 883 patients and a validation cohort of 343 patients. The model used LASSO regression for feature optimization and multivariable logistic regression to develop the predictive model. Model accuracy was assessed via the receiver operating characteristic curve, with further evaluation of calibration and clinical utility through calibration curves and decision curve analysis (DCA). The model underwent internal validation using bootstrapping and external validation with the validation cohort.

Older age (OR 1.07, p=0.005), higher degrees of carotid stenosis (OR 1.07, p=0.006), poor collateral circulation (OR 6.26, p<0.001), elevated preoperative triglyceride levels (OR 1.27, p=0.041) and neutrophil counts (OR 1.36, p<0.001) were identified as independent risk factors for HICH during hospitalization. The nomogram constructed based on these predictive factors demonstrated an area under the curve (AUC) of 0.817. The AUCs for internal and external validation were 0.809 and 0.783, respectively. Calibration curves indicated good model fit, and DCA confirmed substantial clinical net benefit in both cohorts.

We developed and validated a nomogram to predict HICH in patients with carotid stenosis post-stenting, facilitating early identification and preventive intervention in high-risk individuals.

The aim of this research was to develop and internally validate a nomogram for forecasting the length of hospital stay following laparoscopic appendectomy in pediatric patients diagnosed with appendicitis.

We developed a prediction model based on a training dataset of 415 pediatric patients with appendicitis, and hospitalization data were collected retrospectively from January 2021 and December 2022. The primary outcome measure in this study was hospital length of stay (LOS), with prolonged LOS defined as admission for a duration equal to or exceeding the 75th percentile of LOS, including the discharge day. Risk factor analysis was conducted through univariate and multivariate logistic regression analyses. Based on the regression coefficients, a nomogram prediction model was developed. The discriminative performance of the predicting model was evaluated using the C-index, and an adjusted C-index was computed through bootstrapping validation. Calibration curves were generated to assess the accuracy of the nomogram. Decision curve analysis was conducted to determine the clinical utility of the predicting model.

Predictors contained in the prediction nomogram included Age, neutrophil-to-lymphocyte ratio, C-reactive protein level, operative time, appendiceal fecalith, and drainage tube. The C-index of the prediction nomogram was determined to be 0.873 (95% CI: 0.838-0.908), with a corrected C-index of 0.8625 obtained through bootstrapping validation (1,000 resamples), indicating the model's favorable discrimination. Calibration curves illustrated a strong agreement between predicted and observed outcomes. According to the decision curve analysis of the nomogram, the predictive model demonstrates a net benefit at threshold probabilities exceeding 2%.

This nomogram, incorporating variables such as Age, neutrophil-to-lymphocyte ratio, C-reactive protein level, operative time, appendiceal fecalith, and drainage tube, offers a convenient method for assessing the duration of hospitalization in pediatric patients with appendicitis.

Acute ischemic stroke represents a critical, life-threatening condition affecting the central nervous system. Intravenous thrombolysis with tissue plasminogen activator (tPA) remains a cornerstone for achieving vascular recanalization in such patients; however, its therapeutic utility is limited, with only approximately 10% of patients benefiting due to the narrow therapeutic window and significant risk of hemorrhagic transformation. Enhancing the efficacy of tPA thrombolysis is therefore imperative. Neutrophils have been identified as key modulators of thrombolytic outcomes, interacting with tPA post-stroke to influence treatment effectiveness. The binding of tPA to low-density lipoprotein receptor-related protein 1 (LRP-1) on neutrophil surfaces induces degranulation and formation of neutrophil extracellular traps (NETs). Conversely, neutrophils impede the thrombolytic action of tPA by obstructing its interaction with fibrin and activating platelets. These findings suggest that targeting neutrophils may hold promise for improving thrombolysis outcomes. This review explores the role of neutrophils in tPA-mediated thrombolysis following acute ischemic stroke, examines neutrophil-associated biomarkers, and outlines potential strategies for enhancing tPA efficacy.

Acute ischemic stroke (AIS) retains a notable stance in global disease burden, with thrombolysis via recombinant tissue plasminogen activator (rtPA) serving as a viable management approach, albeit with variable outcomes and the potential for complications like hemorrhagic transformation (HT). The platelet-to-neutrophil ratio (P/NR) has been considered for its potential prognostic value in AIS, yet its capacity to predict outcomes following rtPA administration demands further exploration.

To elucidate the prognostic utility of P/NR in predicting HT and clinical outcomes following intravenous rtPA administration in AIS patients.

Data from 418 AIS patients treated with intravenous rtPA at Thammasat University Hospital from January 2018 to June 2021 were retrospectively analyzed. The relationship between P/NR and clinical outcomes [early neurological deterioration (E-ND), HT, delayed ND (D-ND), and 3-mo outcomes] was scrutinized.

Notable variables, such as age, diabetes, and stroke history, exhibited statistical disparities when comparing patients with and without E-ND, HT, D-ND, and 3-mo outcomes. P/NR prognostication revealed an optimal cutoff of 43.4 with a 60.3% sensitivity and a 52.5% specificity for 90-d outcomes. P/NR prognostic accuracy was statistically significant for 90-d outcomes [area under the curve (AUC) = 0.562], D-ND (AUC = 0.584), and HT (AUC = 0.607).

P/NR demonstrated an association with adverse 3-mo clinical outcomes, HT, and D-ND in AIS patients post-rtPA administration, indicating its potential as a predictive tool for complications and prognoses. This infers that a diminished P/NR may serve as a novel prognostic indicator, assisting clinicians in identifying AIS patients at elevated risk for unfavorable outcomes following rtPA therapy.

The dramatic clinical improvement offered by mechanical thrombectomy raised questions about the relevance of prior intravenous thrombolysis in large-vessel occlusion strokes. Hence, studying intravenous thrombolysis susceptibility and its dependence on thrombus composition is crucial. We used an observational proteomic study of whole thrombi retrieved by mechanical thrombectomy to identify factors associated with fibrin content and fibrinolytic activity (FA).

In 104 stroke patients, the thrombi proteome was established by mass spectrometry coupled to liquid chromatography. FA was estimated in clots both outside (FAout) by measuring D-dimer levels at the blood-thrombus interface and inside (FAin) by evaluating the ratio of fibrinogen α to its plasmin-cleaved forms using proteomics coupled with protein electrophoresis. The factors associated with fibrin content, FAin, and FAout were determined by intravenous thrombolysis-adjusted linear regression.

FAout (P<0.0001) and FAin (P=0.0147) were driven by recombinant tissue-type plasminogen activator (r-tPA) administration (47/104) and thrombus composition. Indeed, FAout was greater with fibrin-rich than erythrocyte-rich thrombi, presumably because of more (r)tPA substrates. Thus, FAout was increased with cardioembolic thrombi (72/104), which are rich in fibrin (P=0.0300). Opposite results were found inside the thrombus, suggesting that (r)tPA penetrability was hampered by the density of the fibrinous cap. Moreover, blood cells had a strong impact on thrombus structure and susceptibility to (r)tPA. Indeed, fibrin content was negatively associated with erythrocyte-specific proteins in the thrombus, admission hematocrit (P=0.0139), and hemoglobin level (P=0.0080), which underlines the key role of erythrocytes in thrombus composition. Also, an increased number of neutrophils impaired FAout (P=0.0225), which suggests that their aggregation around the thrombus prevented the (r)tPA attack. Only FAout was significantly associated with reduced thrombus weight (P=0.0310), increased recanalization rate (P=0.0150), good clinical outcome (P=0.0480), and reduced mortality (P=0.0080).

Proteomics can offer new insights into the close relationship between thrombus composition and susceptibility to fibrinolysis, paving the way for new adjuvant therapies.

Intracerebral hemorrhage (ICH) is the cerebrovascular disease with the highest disability and mortality rates, causing severe damage to the health of patients and imposing a significant socioeconomic burden. Aging stands as a foremost risk factor for ICH, with a significant escalation in ICH incidence within the elderly demographic, highlighting a close association between ICH and aging. In recent years, with the acceleration of the "aging society" trend, exploring the intricate relationship between aging and ICH has become increasingly urgent and worthy of in-depth attention. We have summarized the characteristics of ICH in the elderly, reviewing how aging influences the onset and development of ICH by examining its etiology and the mechanisms of damage via ICH. Additionally, we explored the potential impacts of ICH on accelerated aging, including its effects on cognitive abilities, quality of life, and lifespan. This review aims to reveal the connection between aging and ICH, providing new ideas and insights for future ICH research.

The purpose of this prospective study was to evaluate the association of systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI), with PSCI in patients with acute ischemic stroke (AIS).

First-onset AIS patients were consecutively included from January 1, 2022 to March 1, 2023. The baseline information was collected at admission. Fasting blood was drawn the next morning. Cognitive function was assessed by the Montreal Cognitive Assessment (MoCA) 3 months after onset. Logistic regression analysis was performed to explore the correlation between SII, SIRI, and PSCI. Receiver operating characteristic (ROC) was conducted to evaluate the predictive ability of SII.

332 participants were recruited, and 193 developed PSCI. Compared with patients without PSCI, the patients with PSCI had higher SII (587.75 (337.42, 988.95) vs. 345.66 (248.44, 572.89), P<0.001) and SIRI (1.59 (0.95, 2.84) vs. 1.02 (0.63, 1.55), P=0.007). SII and SIRI negatively correlated with MoCA scores (both P<0.05). The multivariable logistic regression analysis indicated that SII was independently associated with PSCI (P<0.001), while SIRI was not. The optimal cutoff for SII to predict PSCI was 676.83×109/L.

A higher level of SII upon admission was independently correlated to PSCI three months later in AIS patients.

The aging of the global population poses significant scientific challenges. Moreover, the biological process of aging is the most significant risk factor for most chronic illnesses; therefore, understanding the molecular and cellular mechanisms underlying these aging-related challenges is crucial for extending the healthy lifespan of older individuals. Preventing brain aging remains a priority public health goal, and integrative and comprehensive aging analyses have revealed that immunosenescence is a potential cause of age-related brain damage and disease (e.g., stroke). Importantly, the neuroinflammatory and immune systems present two-way contact and thus can affect each other. Emerging evidence supports the numerous effects of immunosenescence- and inflammation-mediated immunity in neurologically injured brains. In this study, we briefly outline how aging alters the pathophysiology and transcriptional amplitude in patients who experienced stroke and then discuss how the immune system and its cellular components and molecular mechanisms are affected by age after stroke. Finally, we highlight emerging interventions with the potential to slow down or reduce aging and prevent stroke onset.

Stroke triggers a systemic inflammatory response over the ensuing days after the cerebral insult. The age and comorbidities of the stroke population make them a vulnerable population for low muscle mass and sarcopenia, the latter being another clinical condition that is closely associated with inflammation, as shown by increased levels of pro-inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR). In this study, we evaluated the relationship between post-stroke NLR changes and muscle mass in a prospective cohort of acute ischemic stroke patients (n = 102) enrolled in the Muscle Assessment in Stroke Study Turkey (MASS-TR). Admission lumbar computed tomography images were used to determine the cross-sectional muscle area of skeletal muscles at L3 vertebra level and calculate the skeletal muscle index (SMI). The median (IQR) SMI was 44.7 (39.1-52.5) cm2/m2, and the NLR at admission and follow-up were 4.2 (3.0-10.5) and 9.4 (5.7-16.2), respectively. While there was no relationship between SMI and admission NLR, a significant inverse correlation was observed between SMI and follow-up NLR (r =  - 0.26; P = 0.007). Lower SMI remained significantly associated (P = 0.036) with higher follow-up NLR levels in multivariate analysis. Our findings highlight the importance of muscle mass as a novel factor related to the level of post-stroke stress response.

Inflammation plays an important role in numerous central nervous system (CNS) disorders. Its role is ambiguous-it can induce detrimental effects, as well as repair and recovery. In response to injury or infection, resident CNS cells secrete numerous factors that alter blood-brain barrier (BBB) function and recruit immune cells into the brain, like neutrophils. Their role in the pathophysiology of CNS diseases, like multiple sclerosis (MS) and stroke, is highly recognized. Neutrophils alter BBB permeability and attract other immune cells into the CNS. Previously, neutrophils were considered a homogenous population. Nowadays, it is known that various subtypes of these cells exist, which reveal proinflammatory or immunosuppressive functions. The primary goal of this review was to discuss the current knowledge regarding the important role of neutrophils in MS and stroke development and progression. As the pathogenesis of these two disorders is completely different, it gives the opportunity to get insight into diverse mechanisms of neutrophil involvement in brain pathology. Our understanding of the role of neutrophils in CNS diseases is still evolving as new aspects of their activity are being unraveled. Neutrophil plasticity adds another level to their functional complexity and their importance for CNS pathophysiology.

No evidence has established a direct causal relationship between early microcirculation disturbance after aneurysmal subarachnoid hemorrhage (aSAH) and neurological function prognosis, which is the key pathophysiological mechanism of early brain injury (EBI) in patients with aSAH.

A total of 252 patients with aSAH were enrolled in the Neurosurgical Intensive Care Unit of Southwest Hospital between January 2020 and December 2022 and divided into the no neurological deterioration, early neurological deterioration, and delayed neurological deterioration groups. Indicators of microcirculation disorders in EBI included regional cerebral oxygen saturation (rSO2) measured by near-infrared spectroscopy (NIRS), brain oxygen monitoring, and other clinical parameters for evaluating neurological function and determining the prognosis of patients with aSAH.

Our data suggest that the rSO2 is generally lower in patients who develop neurological deterioration than in those who do not and that there is at least one time point in the population of patients who develop neurological deterioration where left and right cerebral hemisphere differences can be significantly monitored by NIRS. An unordered multiple-classification logistic regression model was constructed, and the results revealed that multiple factors were effective predictors of early neurological deterioration: reoperation, history of brain surgery, World Federation of Neurosurgical Societies (WFNS) grade 4-5, Fisher grade 3-4, SAFIRE grade 3-5, abnormal serum sodium and potassium levels, and reduced rSO2 during the perioperative period. However, for delayed neurological deterioration in patients with aSAH, only a history of brain surgery and perioperative RBC count were predictive indicators.

The rSO2 concentration in patients with neurological deterioration is generally lower than that in patients without neurological deterioration, and at least one time point in the population with neurological deterioration can be significantly monitored via NIRS. However, further studies are needed to determine the role of microcirculation and other predictive factors in the neurocritical management of EBI after aSAH, as these factors can reduce the incidence of adverse outcomes and mortality during hospitalization.

Inflammation is associated with unfavorable clinical outcomes after aneurysmal subarachnoid hemorrhage (aSAH). We evaluated the relationship between postoperative neutrophil-to-albumin ratio (NAR) and unfavorable clinical outcomes (modified Rankin score ≥ 3) at hospital discharge in aSAH patients.

Five hundred sixty aSAH patients undergoing surgical or endovascular treatment were included in this retrospective study. Patients were initially allocated to high (n=247) or low (n=313) postoperative NAR groups based on the immediate postoperative NAR cutoff value identified by receiver operating characteristic analysis, and then further subclassified into 4 groups: HH (high pre- and high postoperative NAR, n=156), LH (low preoperative and high postoperative NAR, n=91), HL (high preoperative and low postoperative NAR, n=68), and low pre- and low postoperative NAR (n=245).

Optimum cutoff values of immediate postoperative and preoperative NAR were 2.45 and 2.09, respectively. Unfavorable clinical outcomes were more frequent in patients with high compared with low postoperative NAR (45.3% vs. 13.4%; P < 0.001). In multivariate analysis, postoperative NAR was a significant predictor of unfavorable clinical outcomes (odds ratio, 2.10; 95% CI, 1.42-3.10; P < 0.001). Unfavorable clinical outcomes were less frequent in group low pre- and low postoperative NAR than in groups HH, LH, and HL (9.4% vs. 44.9%, 46.2% and 27.9%, respectively; all P < 0.001) and also in Group HL compared with groups HH and LH ( P =0.026 and P =0.030); clinical outcomes did not differ between Groups HH and LH.

A high immediate postoperative NAR was associated with unfavorable clinical outcomes at hospital discharge in aSAH patients.

Accumulating evidence indicates that neutrophil activation (NA) contributes to microvascular thromboinflammation in acute ischemic stroke (AIS) due to a large vessel occlusion. Preclinical data have suggested that intravenous thrombolysis (IVT) before endovascular therapy (EVT) could dampen microvascular thromboinflammation. In this study we investigated the association between NA dynamics and stroke outcome, and the impact of IVT on NA in patients with AIS treated with EVT.

A single-center prospective study was carried out, including patients treated with EVT for whom three blood samples (before, within 1 hour, 24 hours post-EVT) were drawn to measure plasma myeloperoxidase (MPO) concentration as a marker of NA. Unfavorable outcome was defined as a modified Rankin score of 3-6 at 3 months.

Between 2016 and 2020, 179 patients were included. The plasma MPO concentration peaked significantly 1 hour post-EVT (median increase 21.0 ng/mL (IQR -2.1-150)) and returned to pre-EVT baseline values 24 hours after EVT (median change from baseline -0.8 ng/mL (IQR -7.6-6.7)). This peak was strongly associated with unfavorable outcomes at 3 months (aOR 0.53 (95% CI 0.34 to 0.84), P=0.007). IVT before EVT abolished this 1 hour post-EVT MPO peak. Changes in plasma MPO concentration (baseline to 1 hour post-EVT) were associated with unfavorable outcomes only in patients not treated with IVT before EVT (aOR 0.54 (95% CI 0.33 to 0.88, P=0.013). However, we found no significant heterogeneity in the associations between changes in plasma MPO concentration and outcomes.

A peak in plasma MPO concentration occurs early after EVT and is associated with unfavorable outcomes. IVT abolished the post-EVT MPO peak and may modulate the association between NA and outcomes.

To evaluate the prognostic performance of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) for mortality in patients with acute stroke treated at a Peruvian hospital.

Retrospective cohort study.

Tertiary care hospital.

Patients aged ≥18 years with a diagnosis of acute stroke and admitted to the hospital from May 2019 to June 2021.

None.

Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and mortality.

A total of 165 patients were included. The mean age was 66.1±14.2 years, and 59.4% were male. Only NLR had a performance superior to 0.7 (AUC: 0.75; 95%CI: 0.65-0.85), and its elevated levels were associated with an increased risk of mortality (aRR: 3.66; 95%CI: 1.77-8.85) after adjusting for confounders.

The neutrophil-to-lymphocyte ratio has an acceptable prognostic performance for mortality in patients with acute stroke. Its use may be considered to stratify patients' risk and to consider timely alternative care and management.

To investigate the relationship between clinical routine inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), white blood cell count (WBC), neutrophils, lymphocytes, and platelets with clinical outcomes in acute basilar artery occlusion (BAO) patients receiving endovascular treatment (EVT).

We recruited 2134 acute BAO patients from 48 stroke centers across 22 Chinese provinces in the ATTENTION registry from 2017 to 2021. Blood samples were drawn at admission. An unfavorable functional outcome was defined using a modified Rankin Scale (mRS) of 4-6 at 90 days. Safety outcomes included mortality within 90 days and symptomatic intracerebral hemorrhage within 3 days.

A total of 1044 patients were included in the final study. After adjusting for confounding factors, the upper quartiles of WBC and NLR were related to 90-day unfavorable functional outcome (mRS = 4-6) compared with those in the lowest quartile (WBC: quartile 4, odds ratio (OR) = 1.85, 95% confidence interval (CI) = 1.22-2.80; NLR: quartile 4, OR = 2.02, 95% CI = 1.34-3.06). The higher quartiles of WBC and NLR were also related to the increased risk of mortality at 90 days. Restricted cubic spline regression analysis showed an incremental trend between NLR and 90-day unfavorable functional outcome (Pnonlinearity = 0.055). In subgroup analysis, a significant interaction was found between NLR and bridging therapy for predicting unfavorable functional outcome (P = 0.006).

Higher WBC and NLR on admission are significantly related to unfavorable functional outcome and mortality at 90 days in acute BAO patients receiving EVT. Significant interaction was found between increased NLR and bridging therapy on these outcome measures.

The neutrophil-to-lymphocyte ratio (NLR) has been found to be useful in the prognostication of immune-mediated neurological disorders because it roughly reflects the systemic innate immune response compared to the adaptive immune response. However, studies on the validity of NLR in demyelinating disorders of the central nervous system have shown conflicting results. Therefore, we aimed to investigate NLR in the idiopathic transverse myelitis (ITM) cohort.

We retrospectively analyzed the cohort data of patients with ITM between January 2006 and February 2020. The medical data of all patients with myelitis were reviewed to exclude patients with disease-associated myelopathy according to predefined exclusion criteria. The relationship between the natural log-transformed NLR (lnNLR) and the clinical, paraclinical, and imaging data was evaluated. Factors associated with neurological disability were analyzed using a linear mixed-effects model. Predictive factors for moderate-to-severe neurological disability (Expanded Disability Status Scale [EDSS] score ≥ 4) were investigated.

A total of 124 participants were included in the analysis. The lnNLR correlated with EDSS and lesion length. Linear mixed-effects analysis showed that age, lesion length, and lnNLR were independently associated with neurological disabilities. Multivariable logistic regression revealed that lnNLR (odds ratio [OR] = 4.266, 95% confidence interval [CI] = 1.220-14.912, p = 0.023) and lesion length (OR = 1.848, 95% CI = 1.249-2.734, p = 0.002) were independent predictive factors of the worst neurological disability.

NLR may be used as an independent prognostic factor for predicting poor neurological outcomes in patients with ITM.

The neutrophil-to-lymphocyte ratio (NLR) has been demonstrated as a prognostic inflammatory biomarker in ischemic stroke. The study aimed to investigate the association of NLR and its dynamic change with long-term outcome and mortality in acute ischemic stroke (AIS) patients who received intravenous thrombolysis (IVT).

From a prospective cohort, AIS patients receiving IVT (alteplase, 0.9 mg/kg) with complete NLR data were retrospectively screened. Based on 3-month modified Rankin scale score (mRS), patients were classified into good group (mRS 0-1) and poor outcome group (mRS 2-6), or survival group (mRS 0-5) and death group (mRS 6). Multivariate logistic regression analysis and receiver operating curve were used to identify prognostic factors and their predictive powers.

A total of 259 eligible patients were enrolled in our study. Logistic regression analysis showed that NLR at 24 h (adjusted odds ratio [aOR] 1.182), 12 days (aOR 1.218) after IVT was independent predictors of 3-month outcome with the AUC of 0.815, 0.820, respectively, whereas NLR at 24 h (aOR 1.17), 12 days (aOR 1.252) after IVT and percentage changes of NLR between admission and 24 h after IVT (aOR 1.214), and between admission and 12 days after IVT (aOR 1.233) were independent predictors of 3-month mortality with the AUCs of 0.86, 0.902, 0.814, and 0.855, respectively.

The comprehensive report suggests that NLR and its dynamic changes are associated with 3-month outcome and mortality in AIS patients after IVT with good predictive powers.

Whether time window affects the intravenous thrombolysis (IVT) effect before endovascular thrombectomy (EVT) is uncertain. We aimed to investigate the effect of different time windows (0-3 h and >3-4.5 h from stroke onset to randomization) on clinical outcomes of EVT with or without IVT in a subgroup analysis of DIRECT-MT.

The primary outcome was the 90-day modified Rankin Scale (mRS) according to time window. Logistic regression models were used to analyze the effect of different treatments (EVT with or without IVT) on outcomes within 0-3 h or >3-4.5 h.

Among 656 patients who were included in the analysis, 282 (43.0%) were randomized within >3-4.5 h after stroke onset (125 without IVT and 157 with IVT), and 374 (57.0%) were randomized within 0-3 h (202 without IVT and 172 with IVT). We noted no significant difference in the thrombectomy-alone effect between the time window subgroups according to 90-day ordinal mRS (adjusted common odds ratio [acOR] in patients within 0-3 h: 1.06 [95% CI: 0.73-1.52], acOR in patients within >3-4.5 h: 1.19 [95% CI: 0.78-1.82]) and 90-day functional independence. Thrombectomy alone resulted in an increased proportion of patients with 90-day mRS 0-3 treated within >3-4.5 h (62.90 vs. 48.72%) but not within 0-3 h (65.84 vs. 63.95%). However, there was no interaction effect regarding all outcomes after the Bonferroni correction.

Our results did not support thrombectomy-alone administration within 3-4.5 h in patients with acute ischemic stroke from large-vessel occlusion in the subgroup analysis of DIRECT-MT.

Patients with acute ischemic stroke are at a high risk of venous thromboembolism (VTE), such as deep vein thrombosis (DVT), estimated to affect approximately 80,000 patients with stroke each year in the United States. The prevalence of symptomatic DVT after acute stroke is approximately 10%. VTE is associated with increased rates of in-hospital death and disability, with higher prevalence of in-hospital complications and increased 1-year mortality in patients with stroke. Current guidelines recommend the use of pharmacologic VTE prophylaxis in patients with acute ischemic stroke. However, thromboprophylaxis prevents only half of expected VTE events and is associated with high risk of bleeding, suggesting the need for targeted alternative treatments to reduce VTE risk in these patients. Neutrophils are among the first cells in blood to respond after ischemic stroke. Importantly, coordinated interactions among neutrophils, platelets, and endothelial cells contribute to the development of DVT. In case of stroke and other related immune disorders, such as antiphospholipid syndrome, neutrophils potentiate thrombus propagation through the formation of neutrophil-platelet aggregates, secreting inflammatory mediators, complement activation, releasing tissue factor, and producing neutrophil extracellular traps. In this illustrated review article, we present epidemiology and management of poststroke VTE, preclinical and clinical evidence of neutrophil hyperactivation in stroke, and mechanisms for neutrophil-mediated VTE in the context of stroke. Given the hyperactivation of circulating neutrophils in patients with stroke, we propose that a better understanding of molecular mechanisms leading to neutrophil activation may result in the development of novel therapeutics to reduce the risk of VTE in this patient population.

There is little knowledge of the effect of inflammatory markers on the prognoses of hematoma expansion (HE) in patients with intracranial hemorrhage (ICH). We evaluated the impact of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) on HE and worse outcomes after acute ICH. This study included 520 consecutive patients with ICH from the registry database enrolled over 80 months. Patients' whole blood samples were collected upon arrival in the emergency department. Brain computed tomography scans were performed during hospitalization and repeated at 24 h and 72 h. The primary outcome measure was HE, defined as relative growth >33% or absolute growth <6 mL. A total of 520 patients were enrolled in this study. Multivariate analysis showed that NLR and PLR were associated with HE (NLR: odds ratio [OR], [95% CI] = 1.19 [1.12-1.27], p < 0.001; PLR: OR, [95% CI] = 1.01 [1.00-1.02], p = 0.04). Receiver operating characteristic curve analysis revealed that NLR and PLR could predict HE (AUC of NLR: 0.84, 95% CI [0.80-0.88], p < 0.001; AUC of PLR: 0.75 95% CI [0.70-0.80], p < 0.001). The cut-off value of NLR for predicting HE was 5.63, and that of PLR was 23.4. Higher NLR and PLR values increase HE risk in patients with ICH. NLR and PLR were reliable for predicting HE after ICH.

Neutrophil serine proteinases (NSPs), released by activated neutrophils, are key proteins involved in the pathophysiologic processes of stroke. NSPs are also implicated in the process and response of thrombolysis. This study aimed to analyze three NSPs (neutrophil elastase, cathepsin G, and proteinase 3) in relation to acute ischemic stroke (AIS) outcomes and in relation to the outcomes of patients treated with intravenous recombinant tissue plasminogen activator (IV-rtPA).

Among 736 patients prospectively recruited at the stroke center from 2018 to 2019, 342 patients diagnosed with confirmed AIS were included. Plasma neutrophil elastase (NE), cathepsin G (CTSG), and proteinase 3 (PR3) concentrations were measured on admission. The primary endpoint was unfavorable outcome defined as modified Rankin Scale score 3-6 at 3 months, and the secondary endpoints were symptomatic intracerebral hemorrhage (sICH) within 48 h, and mortality within 3 months. In the subgroup of patients who received IV-rtPA, post-thrombolysis early neurological improvement (ENI) (defined as National Institutes of Health Stroke Scale score = 0 or decrease of ≥ 4 within 24 h after thrombolysis) was also included as the secondary endpoint. Univariate and multivariate logistic regression analyses were performed to evaluate the association between NSPs levels and AIS outcomes.

Higher NE and PR3 plasma levels were associated with the 3-month mortality and 3-month unfavorable outcome. Higher NE plasma levels were also associated with the risk of sICH after AIS. After adjusting for potential confounders, plasma NE level > 229.56 ng/mL (odds ratio [OR] = 4.478 [2.344-8.554]) and PR3 > 388.77 ng/mL (OR = 2.805 [1.504-5.231]) independently predicted the 3-month unfavorable outcome. Regarding rtPA treatment, patients with NE plasma concentration > 177.22 ng/mL (OR = 8.931 [2.330-34.238]) or PR3 > 388.77 ng/mL (OR = 4.275 [1.045-17.491]) were over 4 times more likely to suffer unfavorable outcomes after rtPA treatment. The addition of NE and PR3 to clinical predictors of unfavorable functional outcome after AIS and the outcome after rtPA treatment improved discrimination as well as reclassification (integrated discrimination improvement = 8.2% and 18.1%, continuous net reclassification improvement = 100.0% and 91.8%, respectively).

Plasma NE and PR3 are novel and independent predictors of 3-month functional outcomes after AIS. Plasma NE and PR3 also possess predictive value to identify patients with unfavorable outcomes after rtPA treatment. NE is probably an important mediator of the effects of neutrophils on stroke outcomes, which worth further investigation.

Leukocytes are systematic inflammation indicators related to stroke prognosis and can exhibit large dynamic waves before and after recombinant tissue plasminogen activator (r-tPA) therapy. However, additional evidence is needed to determine the prognostic significance of various leukocytes including both static and dynamic data among patients who underwent r-tPA therapy. A total of 251 patients treated with r-tPA were included; their leukocyte data were collected at two time points, and patients were followed up for three months. Analysis revealed the following findings. (i) Patients with hemorrhagic transformation (HT) and unfavorable outcomes had a higher level of leukocytes after r-tPA therapy (leukocyte count (adjusted OR (aOR) 1.191 for HT and 1.184 for unfavorable outcomes), neutrophil count (aOR 1.215 and 1.214), neutrophil-to-lymphocyte ratio (NLR; aOR 1.084 and 1.091)) and larger dynamic leukocyte changes. (ii)Among all leukocytes, the NLR after r-tPA administration demonstrated the strongest correlation with HT and unfavorable outcomes. (iii) Patients with an NLR ≥ 3.322 had a 3.492-fold increased risk for HT, and those with an NLR ≥ 5.511 had a 3.024-fold increased risk for functional outcomes. Overall, this study shows that leukocytes, especially leukocyte count, neutrophil count and the NLR, are independently associated with HT and functional outcomes in stroke patients.

Spontaneous intracerebral hemorrhage (ICH) usually occurs in the basal ganglia and is highly lethal and disabling. The aim of this study was to evaluate the predictors of 30-day mortality in patients with severe spontaneous basal ganglia hemorrhage.

This retrospective study included patients with severe basal ganglia intracerebral hemorrhage treated in the Third Affiliated Hospital of Soochow University from 2012 to 2018. Demographic, clinical, laboratory and neuroradiological data were collected. The short-term prognosis was evaluated and divided into death within 30-days and survival over 30-days. We studied the factors affecting the prognosis of patients with severe intracerebral hemorrhage, analyzed the parameters related to neutrophil-to-lymphocyte (NLR) at admission, and evaluated the predictive effect of NLR on 30-day mortality.

A total of 105 patients was included in this retrospective study. The 30-day death group had a larger hematoma, a higher probability of ventricular hemorrhage, a higher ICH score and a lower Glasgow Coma Scale (GCS) score on admission. Meanwhile, the patients in the death group had higher White blood cells (WBC) counts, neutrophil counts, NLRs and C-reactive protein (CRP) levels. The risk factors for 30-day death were related to the ICH volume, GCS score, ICH score, WBC count, neutrophil count, NLR and CRP. The univariate receiver operating characteristic (ROC) curve of the risk factors showed that the NLR had the best prediction performance. Mathematical predictive models for ICH patients showed that the model with NLR had better prediction accuracy.

The NLR is expected to be a potential biomarker for predicting the prognosis of patients with severe basal ganglia hemorrhage.

Background: Neutrophil-to-lymphocyte ratio (NLR), a systemic inflammatory biomarker, has been associated with poorer outcomes in acute ischemic stroke patients. The present study was designed to expand these findings by investigating the association between NLR and short-term functional outcomes in acute ischemic stroke patients. Methods: This retrospective study evaluated patients within 7 days after the onset of acute ischemic stroke. Stroke severity on admission was measured using the National Institutes of Health Stroke Scale (NIHSS). The functional outcomes were assessed using the Berg Balance Scale (BBS), Manual Function Test (MFT), the Korean version of the modified Barthel Index (K-MBI), and the Korean Mini-Mental State Examination (K-MMSE) within 2 weeks of stroke onset. The modified Rankin Scale (mRS) was evaluated at discharge. Results: This study included 201 patients, who were grouped into three NLR tertiles (<1.84, 1.84−2.71, and >2.71) on admission. A multivariate analysis showed that the top tertile group (NLR > 2.71) had significantly higher risks of unfavorable outcomes on the K-MBI (p = 0.010) and K-MMSE (p = 0.029) than the bottom tertile group (NLR < 1.84). Based on the optimal cut-off values from a receiver operating characteristic curve analysis, a higher NLR was significantly associated with higher NIHSS scores (p = 0.011) and unfavorable outcomes on the K-MBI (p = 0.002) and K-MMSE (p = 0.001). Conclusions: A higher NLR is associated with poorer short-term functional outcomes in acute ischemic stroke patients.

Stress hyperglycemia ratio (SHR), which is used to assess stress hyperglycemia, is associated with the functional outcome of ischemic stroke (IS). IS can induce the inflammatory response. Neutrophil counts and neutrophil-to-lymphocyte ratio (NLR) as good and easily available inflammatory biomarkers, the relationship between neutrophil counts and NLR and SHR were poorly explored in IS. We aimed to systemically and comprehensively explore the correlation between various blood inflammation markers (mainly neutrophil counts and NLR) and SHR.

Data from 487 patients with acute IS(AIS) in Xiangya Hospital were retrospectively reviewed. High/low SHR groups according to the median of SHR (≤1.02 versus >1.02). Binary logistic regression analysis was used to evaluate the correlation between neutrophil counts and NLR and high SHR group. Subgroup analyses were performed in the TOAST classification and functional prognosis.

The neutrophil counts and NLR were all clearly associated with SHR levels in different logistic analysis models. In the subgroup analysis of TOAST classification, the higher neutrophil counts and NLR were the independent risk factors for high SHR patients with large-artery atherosclerosis (LAA) (neutrophil: adjusted OR:2.047, 95% CI: 1.355-3.093, P=0.001; NLR: adjusted OR:1.315, 95% CI: 1.129-1.530, P<0.001). The higher neutrophil counts were the independent risk factor for high SHR patients with cardioembolism (CE) (adjusted OR:2.413, 95% CI: 1.081-5.383, P=0.031). ROC analysis showed that neutrophil counts was helpful for differentiating high SHR group with CE and low SHR group with CE (neutrophil: AUC =0.776, P=0.002). However, there were no difference in levels of neutrophil counts and NLR between patients with SVO and without SVO. The higher neutrophil counts and NLR independently associated with high SHR patients with mRS ≤2 at 90 days from symptom onset, (neutrophil: adjusted OR:2.284, 95% CI: 1.525-3.420, P<0.001; NLR: adjusted OR:1.377, 95% CI: 1.164-1.629, P<0.001), but not in patients with mRS >2.

This study found that the neutrophil counts and NLR are positively associated with SHR levels in AIS patients. In addition, the correlation between neutrophil counts and NLR and different SHR levels are diverse according to TOAST classification and functional prognosis.

The prognostic role of the neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, in acute ischemic stroke (AIS) after reperfusion therapy remains controversial. Therefore, this meta-analysis sought to assess the correlation between the dynamic NLR and the clinical outcomes of patients with AIS after reperfusion therapy.

PubMed, Web of Science, and Embase databases were searched to identify relevant literature from their inception to 27 October 2022. The clinical outcomes of interest included poor functional outcome (PFO) at 3 months, symptomatic intracerebral hemorrhage (sICH), and 3-month mortality. The NLR on admission (pre-treatment) and post-treatment was collected. The PFO was defined as a modified Rankin scale (mRS) of >2.

A total of 17,232 patients in 52 studies were included in the meta-analysis. The admission NLR was higher in the 3-month PFO (standardized mean difference [SMD] = 0.46, 95% confidence interval [CI] = 0.35-0.57), sICH (SMD = 0.57, 95% CI = 0.30-0.85), and mortality at 3 months (SMD = 0.60, 95% CI = 0.34-0.87). An elevated admission NLR was associated with an increased risk of 3-month PFO (odds ratio [OR] = 1.13, 95% CI = 1.09-1.17), sICH (OR = 1.11, 95% CI = 1.06-1.16), and mortality at 3 months (OR = 1.13, 95% CI = 1.07-1.20). The post-treatment NLR was significantly higher in the 3-month PFO (SMD = 0.80, 95% CI = 0.62-0.99), sICH (SMD = 1.54, 95% CI = 0.97-2.10), and mortality at 3 months (SMD = 1.00, 95% CI = 0.31-1.69). An elevated post-treatment NLR was significantly associated with an increased risk of 3-month PFO (OR = 1.25, 95% CI = 1.16-1.35), sICH (OR = 1.14, 95% CI = 1.01-1.29), and mortality at 3 months (OR = 1.28, 95% CI = 1.09-1.50).

The admission and post-treatment NLR can be used as cost-effective and easily available biomarkers to predict the 3-month PFO, sICH, and mortality at 3 months in patients with AIS treated with reperfusion therapy. The post-treatment NLR provides better predictive power than the admission NLR.

https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022366394.

Hemorrhagic transformation (HT) following reperfusion therapies for acute ischaemic stroke often predicts a poor prognosis. This systematic review and meta-analysis aims to identify risk factors for HT, and how these vary with hyperacute treatment [intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT)].

Electronic databases PubMed and EMBASE were used to search relevant studies. Pooled odds ratio (OR) with 95% confidence interval (CI) were estimated.

A total of 120 studies were included. Atrial fibrillation and NIHSS score were common predictors for any intracerebral hemorrhage (ICH) after reperfusion therapies (both IVT and EVT), while a hyperdense artery sign (OR = 2.605, 95% CI 1.212-5.599, I ² = 0.0%) and number of thrombectomy passes (OR = 1.151, 95% CI 1.041-1.272, I ² = 54.3%) were predictors of any ICH after IVT and EVT, respectively. Common predictors for symptomatic ICH (sICH) after reperfusion therapies were age and serum glucose level. Atrial fibrillation (OR = 3.867, 95% CI 1.970-7.591, I ² = 29.1%), NIHSS score (OR = 1.082, 95% CI 1.060-1.105, I ² = 54.5%) and onset-to-treatment time (OR = 1.003, 95% CI 1.001-1.005, I ² = 0.0%) were predictors of sICH after IVT. Alberta Stroke Program Early CT score (ASPECTS) (OR = 0.686, 95% CI 0.565-0.833, I ² =77.6%) and number of thrombectomy passes (OR = 1.374, 95% CI 1.012-1.866, I ² = 86.4%) were predictors of sICH after EVT.

Several predictors of ICH were identified, which varied by treatment type. Studies based on larger and multi-center data sets should be prioritized to confirm the results.

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=268927, identifier: CRD42021268927.

Stroke is among the leading causes of death and disability worldwide. Restoring blood flow through recanalization is currently the only acute treatment for cerebral ischemia. Unfortunately, many patients that achieve a complete recanalization fail to regain functional independence. Recent studies indicate that activation of peripheral immune cells, particularly neutrophils, may contribute to microcirculatory failure and futile recanalization. Stroke primarily affects the elderly population, and mortality after endovascular therapies is associated with advanced age. Previous analyses of differential gene expression across injury status and age identify ischemic stroke as a complex age-related disease. It also suggests robust interactions between stroke injury, aging, and inflammation on a cellular and molecular level. Understanding such interactions is crucial in developing effective protective treatments. The global stroke burden will continue to increase with a rapidly aging human population. Unfortunately, the mechanisms of age-dependent vulnerability are poorly defined. In this review, we will discuss how neutrophil-specific gene expression patterns may contribute to poor treatment responses in stroke patients. We will also discuss age-related transcriptional changes that may contribute to poor clinical outcomes and greater susceptibility to cerebrovascular diseases.

This study aimed to develop a score including novel putative predictors for predicting the risk of sICH and outcomes after thrombolytic therapy with intravenous (IV) recombinant tissue-type plasminogen activator (r-tPA) in acute ischemic stroke patients.

All patients with acute ischemic stroke treated with IV r-tPA at three university-based hospitals in Chongqing, China, from 2014 to 2019 were retrospectively studied. Potential risk factors associated with sICH (NINDS criteria) were determined with multivariate logistic regression, and we developed our score according to the magnitude of logistic regression coefficients. The score was validated in another independent cohort. Area under the receiver operating characteristic curve (AUC-ROC) was used to assess the performance of the score. Calibration was evaluated using the Hosmer-Lemeshow goodness-of-fit method.

The SON2A2 score (0 to 8 points) consisted of history of smoking (no = 1, yes = 0, β = 0.81), onset-to-needle time (≥3.5 = 1,<3.5=0, β = 0.74), NIH Stroke Scale on admission (>10 = 2, ≤10 = 0, β = 1.22), neutrophil percentage (≥80.0% = 1, <80% = 0, β = 0.81), ASPECT score (≤11 = 2, >11 = 0, β = 1.30), and age (>65 years = 1, ≤65 years = 0, β = 0.89). The SON2A2 score was strongly associated with sICH (OR 1.98; 95%CI 1.675-2.34) and poor outcomes (OR 1.89; 95%CI 1.68-2.13). AUC-ROC in the derivation cohort was 0.82 (95%CI 0.77-0.86). Similar results were obtained in the validation cohort. The Hosmer-Lemeshow test revealed that predicted and observed event rates in derivation and validation cohorts were very close.

The SON2A2 score is a simple, efficient, quick, and easy-to-perform scale for predicting the risk of sICH and outcome after intravenous r-tPA thrombolysis within 4.5 h in patients with ischemic stroke, and risk assessment using this test has the potential for early and personalized management of this disease in high-risk patients.

The worsening of neurological status that occurs early after acute ischemic stroke (AIS) remains a serious issue, and the inflammatory response plays a key role in stroke pathobiology. Recently, endovascular treatment (EVT) has revolutionized the management and outcome of patients with AIS due to either extracranial carotid disease or intracranial disease. The neutrophil-to-lymphocyte ratio (NLR) represents an easily available inflammatory biomarker. The aim of the study was to assess the relationship between the NLR at admission and the occurrence of early neurological deterioration (END) in patients with AIS who underwent EVT. Patients with AIS and proximal arterial occlusion in the anterior circulation undergoing EVT were retrospectively identified. Absolute neutrophil count (ANC) and absolute lymphocyte count (ALC) were collected from admission blood work to calculate the NLR. The study outcome was END defined as an increase in at least 4 points in NIHSS score or death between baseline and 24 h after the ischemic event. Patients included were 211, and END occurred in 30 (14.2%). Patients with older age (OR = 1.07, 95% CI: 1.02−1.13), higher serum glucose (OR = 1.01, 95% CI: 1.01−1.02), and higher NLR (OR = 1.011, 95% CI: 1.04−1.18) had an increased risk of END. The best predictive cut-off value of NLR was 6.4, and END occurred in 24.1% and 3.9% of the patients with NLR ≥ 6.4 and <6.4, respectively (p < 0.001). In patients with AIS undergoing EVT, higher NLR values predicted a higher risk of END. Biomarkers able to identify inflammatory mechanisms might identify novel treatment targets and enhance proof-of-concept trials of immunomodulation in stroke.