Aldehyde Dehydrogenase Isoform 1 Predicts a Poor Prognosis of Acute Cerebral Infarction.

To investigate the prognostic potential of serum aldehyde dehydrogenase isoform 1 (ALDH1) level in acute cerebral infarction, and the molecular mechanism in mediating neurological deficits, a total of 120 acute cerebral infarction cases within 72 h of onset were retrospectively analyzed. Serum ALDH1 level in them was detected by qRT-PCR. Receiver operating characteristic (ROC) and Kaplan-Meier curves were depicted for assessing the diagnostic and prognostic potentials of ALDH1 in acute cerebral infarction, respectively. An in vivo acute cerebral infarction model in rats was established by performing MCAO, followed by evaluation of neurological deficits using mNSS and detection of relative levels of ALDH1, Smad2, Smad4, and p21 in rat brain tissues. Pearson's correlation test was carried out to verify the correlation between ALDH1 and mNSS and relative levels of Smad2, Smad4, and p21. Serum ALDH1 level increased in acute cerebral infarction patients. A high level of ALDH1 predicted a poor prognosis of acute cerebral infarction patients. In addition, ALDH1 was sensitive and specific in distinguishing acute cerebral infarction cases, presenting a certain diagnostic potential. mNSS was remarkably higher in acute cerebral infarction rats than that of controls. Compared with sham operation group, relative levels of ALDH1, Smad2, and Smad4 were higher in brain tissues of modeling rats, whilst p21 level was lower. ALDH1 level in brain tissues of modeling rats was positively correlated to mNSS, and mRNA levels of Smad2 and Smad4, but negatively correlated to p21 level. Serum ALDH1 level is a promising prognostic and diagnostic factor of acute cerebral infarction, which is correlated to 90-day mortality. Increased level of ALDH1 in the brain of cerebral infarction rats is closely linked to neurological function, which is associated with the small mothers against decapentaplegic (Smad) signaling and p21.

BNP on Admission Combined with Imaging Markers of Multimodal CT to Predict the Risk of Cardioembolic Stroke.

Background: The aim of the study was to find the potential roles of B-type natriuretic peptide (BNP) and imaging markers on distinguishing cardioembolic (CE) stroke from non-CE stroke, so as to provide useful information for making individualized endovascular treatment (EVT) plan for the patients with acute ischemic stroke (AIS). Methods: The patients with unilateral anterior circulation large vessel occlusion who underwent EVT between March 2016 and December 2021 were analyzed in this study, retrospectively. The risk factors, laboratory test indicators, imaging parameters, and other factors were compared between the CE group and non-CE group. Logistic regression was used to analyze the risk factors of CE stroke. ROC curves were used to assess the values of different parameters on distinguishing CE stroke from non-CE stroke. The relationships between BNP and imaging parameters were assessed using the Spearman correlation analysis. Results: 160 patients were enrolled in the study and divided into the CE group (n = 66) and non-CE group (n = 94). BNP (odds ratio (OR) = 1.004; 95% CI, 1.001-1.009; p = 0.038), MMR (OR = 0.736; 95% CI, 0.573-0.945; p = 0.016), NIHSS (OR = 1.150; 95% CI, 1.022-1.294; p = 0.020), and AF (OR = 556.968; 95% CI, 51.739-5995.765; p < 0.001) were the independent predictive factors of CE stroke. The area under the curve (AUC) of BNP and mismatch ratio (MMR) were 0.846 (95% CI (0.780-0.898), p < 0.001) and 0.636 (95% CI (0.633-0.779), p < 0.001), respectively. The cut-off value of BNP was 249.23 pg/mL with the sensitivity of 74.24% and the specificity of 82.98%. BNP combined with MMR improved the predictive value for CE stroke. The AUC of the combination was 0.858 with the sensitivity of 84.85% and the specificity of 73.40%. BNP was correlated with 4D CTA collateral score, MMR, clot burden score, final infarct volume, infarct core volume, and ischemic penumbra volume (all, p < 0.05). Conclusion: BNP on admission combined with MMR is valuable for the risk prediction of CE stroke, which will promote the further screening of the high-risk patients with CE stroke and provide more diagnostic information for clinicians.

Higher serum occludin after successful reperfusion Is associated with early neurological deterioration.

AIMS: Early neurological deterioration (END) is an important factor that affects prognosis in patients with acute ischemic stroke. We explored the relationship between serum occludin levels after successful reperfusion and END in patients treated with endovascular thrombectomy (EVT). METHODS: We prospectively enrolled 120 stroke patients who underwent EVT with successful reperfusion. Enzyme-linked immunosorbent assay was used to detect the serum occludin levels on admission and within 1 h after successful reperfusion. Receiver operating characteristic curves (ROC) and regression analysis were used to compare the relationship between serum occludin and END after thrombectomy. RESULTS: Among the 120 patients, 36 (30%) experienced END. The END group had higher serum occludin levels than the non-END group after successful reperfusion [4.31 (3.71-5.38) vs 6.32 (5.88-6.99), p < 0.001]. The ROC curve showed that postoperative serum occludin levels had a significant prediction value for END (AUC: 0.86, p < 0.001). Regression analysis showed that serum occludin was an independent risk factor for END in EVT patients (adjusted odds ratio: 4.46, 95% confidence interval: 1.92-10.32; p < 0.001). CONCLUSIONS: The higher serum occludin levels were strongly related to END after successful reperfusion. Serum occludin may be an independent risk factor for END in EVT patients.

Neutrophils predominate the immune signature of cerebral thrombi in COVID-19 stroke patients.

Coronavirus disease 2019 (COVID-19) is associated with an increased risk of thrombotic events. Ischemic stroke in COVID-19 patients entails high severity and mortality rates. Here we aimed to analyze cerebral thrombi of COVID-19 patients with large vessel occlusion (LVO) acute ischemic stroke to expose molecular evidence for SARS-CoV-2 in the thrombus and to unravel any peculiar immune-thrombotic features. We conducted a systematic pathological analysis of cerebral thrombi retrieved by endovascular thrombectomy in patients with LVO stroke infected with COVID-19 (n = 7 patients) and non-covid LVO controls (n = 23). In thrombi of COVID-19 patients, the SARS-CoV-2 docking receptor ACE2 was mainly expressed in monocytes/macrophages and showed higher expression levels compared to controls. Using polymerase chain reaction and sequencing, we detected SARS-CoV-2 Clade20A, in the thrombus of one COVID-19 patient. Comparing thrombus composition of COVID-19 and control patients, we noted no overt differences in terms of red blood cells, fibrin, neutrophil extracellular traps (NETs), von Willebrand Factor (vWF), platelets and complement complex C5b-9. However, thrombi of COVID-19 patients showed increased neutrophil density (MPO+ cells) and a three-fold higher Neutrophil-to-Lymphocyte Ratio (tNLR). In the ROC analysis both neutrophils and tNLR had a good discriminative ability to differentiate thrombi of COVID-19 patients from controls. In summary, cerebral thrombi of COVID-19 patients can harbor SARS-CoV2 and are characterized by an increased neutrophil number and tNLR and higher ACE2 expression. These findings suggest neutrophils as the possible culprit in COVID-19-related thrombosis.

Early Neutrophil-to-Lymphocyte Ratio Is a Prognostic Marker in Acute Ischemic Stroke After Successful Revascularization.

OBJECTIVE: To explore the association between early neutrophil-to-lymphocyte ratio (ENLR) and prognosis of anterior circulation large-vessel occlusion stroke (LVOS) after patients undergo endovascular treatment (EVT) with successful revascularization. METHODS: Patients who experienced acute anterior circulation LVOS and underwent EVT at Changzhou Second People's Hospital Affiliated to Nanjing Medical University between May 2017 and May 2020 were included in this retrospective study. We collected information about patients' baseline characteristics, medical history, laboratory test results, imaging data, and endovascular treatment outcomes, as well as data from follow-up at 3 months. Univariate and multivariate logistic regression models were used to evaluate the association between ENLR and functional disease prognosis. A piecewise linear regression model was also applied to compute the threshold effect of ENLR on poor prognosis (defined as modified Rankin Scale score 3-6) at 3 months using a smoothing plot. RESULTS: Of 224 patients who received EVT during the study period, 160 patients were included in the analysis. After adjustments were made for potential confounders, multivariate analysis demonstrated a significant association between ENLR and poor prognosis at 3 months (odds radio 1.19; 95% confidence interval 1.07-1.32; P = 0.0016). An ENLR ≥9.75 was found to be significantly associated with poor prognosis at 3 months (odds ratio 1.54; 95% confidence interval 1.19-2.00; P = 0.0119). CONCLUSIONS: Increased ENLR after successful revascularization is independently associated with poor prognosis. These findings suggest that ENLR could be used to inform treatment strategies for patients who experience anterior circulation LVOS.

Predictive effects of admission white blood cell counts and hounsfield unit values on delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Neuroinflammatory response is deemed the primary pathogenesis of delayed cerebral ischemia (DCI) caused by aneurysmal subarachnoid hemorrhage (aSAH). Both white blood cell (WBC) count and Hounsfield Unit (HU) are gradually considered can reflect inflammation in DCI. This study aims to identify the relationship between WBC count and HU value and investigate the effects of both indicators in predicting DCI after aSAH. METHODS: We enrolled 109 patients with aSAH admitted within 24 h of onset in our study. A multivariate logistic regression analysis was used to evaluate the admission WBC count, HU value, and combined WBC-HU associated with DCI. The receiver operating characteristic curve and area under the curve (AUC) were used to determine thresholds and detect the predictive ability of these predictors. These indicators were also compared with the established inflammation markers. RESULTS: Thirty-six (33%) patients developed DCI. Both WBC count and HU value were strongly associated with the admission glucose level (ρ = .303, p = .001; ρ = .273, p = .004), World Federation of Neurosurgical Societies grade (ρ = .452, p < .001; ρ = .578; p < .001), Hunt-Hess grade (ρ = .450, p < .001; ρ = .510, p < .001), and modified Fisher scale score (ρ = .357, p < .001; ρ = .330, p < .001). After controlling these public variables, WBC count (ρ = .300, p = .002) positively correlated with HU value. An early elevated WBC (odds ratio [OR] 1.449, 95% confidence interval [CI]: 1.183-1.774, p < .001) count and HU value (OR 1.304, 95%CI: 1.149-1.479, p < .001) could independently predict the occurrence of DCI. However, only these patients with both WBC count and HU value exceeding the cut-off points (OR 36.89, 95%CI: 5.606-242.78, p < .001) were strongly correlated with DCI. Compared with a single WBC count (AUC 0.811, 95%CI: 0.729-0.892, p < .001) or HU value (AUC 0.869, 95%CI: 0.803-0.936, p < .001), the combined WBC-HU (AUC 0.898, 95%CI: 0.839-0.957, p < .001) demonstrated a better ability to predict the occurrence of DCI. Inspiringly, the prediction performance of these indicators outperformed the established inflammatory markers. CONCLUSION: An early elevated WBC count and HU value could independently predict DCI occurrence between 4 and 30 days after aSAH. Furthermore, WBC count was positively correlated with HU value, and the combined WBC-HU demonstrated a superior prediction ability for DCI development compared with the individual indicator.

Early-stage serum Stanniocalcin 1 as a predictor of outcome in patients with aneurysmal subarachnoid hemorrhage.

ABSTRACT: Stanniocalcin-1 (STC1) takes part in anti-inflammatory and anti-oxidative processes, thus demonstrating neuroprotective properties. Early brain injuries associated with initial subarachnoid hemorrhage typically led to secondary cerebral infarction and poor outcomes. This retrospective study aimed to clarify the clinical significance of serum STC1 level in patients with subarachnoid hemorrhage.We collected demographic information, comorbidities, neurological status in detail. All blood samples were collected on admission. Enzyme-linked immunosorbent assay kits were used to detect the serum level of STC1. Spearman analysis was used to explore the relationship between STC1 and clinical severity. Multivariate logistic regression was used to investigate the prognostic role of STC1 in patients with aneurysmal subarachnoid hemorrhage (aSAH). Receiver operating characteristic curve was performed to investigate the power of STC1 in predicting outcome in aSAH patients.Serum STC1 concentration was significantly higher in aSAH patients than in healthy individuals. Serum concentration of STC1 positively correlated with Hunt-Hess grade (r = 0.62, P < .01) and Fisher grade (r = 0.48, P < .01), and negatively correlated with Glasgow Coma Scale on admission (r = -0.45, P < .01). Patients with delayed cerebral ischemia (DCI) had higher level of serum STC1 than those without DCI (13.12 ±â€Š1.44 vs 8.56 ±â€Š0.31, P < .01). Moreover, patients with poor outcome had higher concentration of STC1 than patients with good outcome (11.82 ±â€Š0.62 vs 8.21 ±â€Š0.35,P < 0.01). Results of univariate and multivariate logistic analysis revealed that Hunt-hess III-IV, DCI, and high STC1 level were independent risk factors associated with poor outcome of patients with aSAH. Further analysis revealed that combination of STC1 with Hunt-hess grade was more superior to 2 indicators alone in predicting clinical outcome of aSAH patients.STC1 can be used as a novel biomarker in predicting outcome of patients with aSAH, especially when combined with Hunt-hess grade.

The Degree of Plasma Oxidized Low-Density Lipoprotein Level Decrease Is Related to Clinical Outcomes for Patients with Acute Ischemic Stroke.

OBJECTIVE: To investigate the relationship between the decrease of plasma oxidized low-density lipoprotein (oxLDL) levels and clinical outcomes in patients with acute atherosclerosis-related ischemic stroke. METHODS: We recruited acute ischemic stroke patients within 3 days of onset consecutively. Plasma oxLDL levels were measured on the second day after admission and before discharge (10-14 days after stroke onset). Initial stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) scores, and infarct volume was measured using diffusion-weighted imaging (DWI) by the ITK-SNAP software. Clinical outcomes were evaluated by DWI volumes in the acute phase, neurological improvement at discharge, and favorable functional prognosis at 90 days. Logistic regression was performed to evaluate the association between oxLDL level decrease and clinical outcomes. RESULTS: 207 patients were enrolled in this study. Compared with the mild decrease of the oxLDL level group, patients with a significant decrease of the oxLDL level group were more likely to have a higher ratio of neurological improvement at discharge (55.07% vs. 14.49%, p < 0.01) and favorable functional prognosis at 90 days (91.30% vs. 55.07%, p < 0.01). In multivariable logistic regression, the degree of oxLDL level decrease was related to neurological improvement at discharge and favorable functional prognosis at 90 days (p < 0.01). Patients with significant decrease were more likely to have neurological improvement at discharge (OR = 7.92, 95% CI, 3.14-19.98, and p < 0.01) and favorable functional prognosis at 90 days (OR = 7.46, 95% CI, 2.40-23.23, and p < 0.01) compared to patients with mild decrease of oxLDL level. The DWI volumes in patients with different oxLDL level decrease groups had no statistical difference (p = 0.41), and the Spearman's rho between oxLDL level decrease and DWI infarct volumes was -0.03, but no statistical difference (p = 0.72). CONCLUSIONS: The degree of oxLDL level decrease is related to neurological improvement at discharge and favorable functional prognosis at 90 days for patients with acute atherosclerosis-related ischemic stroke, but not with infarct volume in the acute phase.

Plasma osteoprotegerin levels are associated with the presence and burden of cerebral small vessel disease in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Osteoprotegerin (OPG) is a component of the tumor necrosis factor receptor superfamily. Several studies have shown a relationship between OPG and cardiovascular diseases. We hypothesized that there is a relationship between plasma OPG levels and cerebral small vessel disease (SVD). METHODS: Patients diagnosed with their first cerebral ischemic infarction between April 2014 and March 2017 were enrolled. All the enrolled patients were evaluated through the hospital stroke protocol, including routine blood tests, brain imaging, and measuring the plasma OPG levels. The presence and burden of cerebral SVD [cerebral microbleeds (CMBs), asymptomatic lacunar infarction (ALI), high-grade perivascular space (HPVS), high-grade white matter hyperintensity (HWMH)], and total SVD score were assessed through brain magnetic resonance imaging. RESULTS: Of the 270 patients included in our study, 158 (58.5%) were men. The mean age of the patients was 63.8 ± 11.6 years. In multivariable analysis, plasma OPG levels were positively associated with the presence and burden of each cerebral SVD. The odds ratios (OR) of CMBs, ALI, HPVS, and HWMH for the association of OPG per standard deviation (SD) increase were 1.58 [95% confidence interval (CI), 1.09-2.27], 1.40 (95% CI, 1.04-1.88), 1.88 (95% CI, 1.27-2.78), and 1.47 (95% CI, 1.04-2.08), respectively. Plasma OPG levels were positively correlated with total SVD score (beta = 0.211, standard error = 0.061, p-value = 0.009, R2 = 0.275). CONCLUSIONS: Plasma OPG levels correlate with the presence and burden of cerebral SVD in patients with acute ischemic stroke.

Calciprotein Particles Link Disturbed Mineral Homeostasis with Cardiovascular Disease by Causing Endothelial Dysfunction and Vascular Inflammation.

An association between high serum calcium/phosphate and cardiovascular events or death is well-established. However, a mechanistic explanation of this correlation is lacking. Here, we examined the role of calciprotein particles (CPPs), nanoscale bodies forming in the human blood upon its supersaturation with calcium and phosphate, in cardiovascular disease. The serum of patients with coronary artery disease or cerebrovascular disease displayed an increased propensity to form CPPs in combination with elevated ionised calcium as well as reduced albumin levels, altogether indicative of reduced Ca2+-binding capacity. Intravenous administration of CPPs to normolipidemic and normotensive Wistar rats provoked intimal hyperplasia and adventitial/perivascular inflammation in both balloon-injured and intact aortas in the absence of other cardiovascular risk factors. Upon the addition to primary human arterial endothelial cells, CPPs induced lysosome-dependent cell death, promoted the release of pro-inflammatory cytokines, stimulated leukocyte adhesion, and triggered endothelial-to-mesenchymal transition. We concluded that CPPs, which are formed in the blood as a result of altered mineral homeostasis, cause endothelial dysfunction and vascular inflammation, thereby contributing to the development of cardiovascular disease.

Serum thromboxane B2 but not soluble P-selectin levels identify ischemic stroke patients with persistent platelet reactivity while on aspirin therapy.

BACKGROUND: Aspirin non-response due to persistent platelet reactivity has been associated with adverse vascular events. Light transmission aggregometry (LTA), the 'gold standard' for measuring the platelet response to aspirin therapy, is a cumbersome procedure and a simple and reliable alternative is required. Our aim was to explore whether serum thromboxane B2 (sTXB2) and soluble P-selectin can be used to identify patients who are at risk of increased platelet reactivity while on aspirin. METHODS AND RESULTS: We recruited 293 ischemic stroke patients, taking aspirin for more than seven days, and performed LTA to classify them. Based on therapeutic serum salicylate levels, 63 patients were excluded due to suspected non-compliance, followed by ELISA measurement of TXB2 and P-selectin in serum. Accordingly, patients were classified into 'Responders' (n = 122, 53%), 'Semi-responders' (n = 76, 33%) and 'Non-responders' (n=32, 14%) by LTA. Patients who had platelet aggregation of ≥70% with 10µM ADP and ≥20% with 0.5mM AA were defined as 'Non-responders'. In comparison with 'Responders', 'Non-responders' had 8.63-fold increased risk of secondary vascular events (p = 0.008). ROC curve analysis revealed that sTXB2, at a cut-off level of >4.15 ng/mL, could distinguish the patient group with elevated platelet reactivity with a sensitivity of 84.3% (AUC = 0.84), and was in fair agreement with the LTA-based classification of patients. Soluble P-selectin levels, on the other hand, had no discriminatory ability. CONCLUSION: We suggest sTXB2 measurement as an alternative to the LTA approach for identifying aspirin-treated ischemic stroke patients who are at risk of enhanced platelet reactivity and subsequent vascular events.

Relation between brain natriuretic peptide and delayed cerebral ischemia in patients with aneurysmalsubarachnoid hemorrhage.

BACKGROUND: Brain natriuretic peptide (BNP), often used to evaluate degree of heart failure, has been implicated in fluid dysregulation and inflammation in critically-ill patients. Twenty to 30% of patients with aneurysmal subarachnoid hemorrhage (aSAH) will develop some degree of neurogenic stress cardiomyopathy (NSC) and in turn elevation of BNP levels. We sought to explore the association between BNP levels and development of delayed cerebral ischemia (DCI) in patients with aSAH. METHODS: We retrospectively evaluated the records of 149 patients admitted to the Neurological Intensive Care Unit between 2006 and 2015 and enrolled in an existing prospectively maintained aSAH database. Demographic data, treatment and outcomes, and BNP levels at admission and throughout the hospital admission were noted. RESULTS: Of the 149 patients included in the analysis, 79 developed DCI during their hospital course. We found a statistically significant association between DCI and the highest recorded BNP (OR 1.001, 95% CI-1.001-1.002, p = 0.002). The ROC curve analysis for DCI based on BNP showed that the highest BNP level during hospital admission (AUC 0.78) was the strongest predictor of DCI compared to the change in BNP over time (AUC 0.776) or the admission BNP (AUC 0.632). CONCLUSION: Our study shows that DCI is associated not only with higher baseline BNP values (admission BNP), but also with the highest BNP level attained during the hospital course and the rapidity of change or increase in BNP over time. Prospective studies are needed to evaluate whether routine measurement of BNP may help identify SAH patients at high risk of DCI.

Dysregulation of miR-637 serves as a diagnostic biomarker in patients with carotid artery stenosis and predicts the occurrence of the cerebral ischemic event.

The present research aims to explore the relationship between circulating microRNA and carotid artery stenosis (CAS). To evaluate the diagnostic significance of miR-637 in CAS patients and its potential predictive value for cerebral ischemia events through clinical studies. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to verify the differences in serum miR-637 between enrolled 97 CAS patients and 90 healthy individuals. Logistic regression analysis of the correlation between the level of miR-637 and the degree of carotid artery stenosis. The receiver operating characteristic (ROC) curve evaluated the diagnostic significance of miR-637 in identifying CAS patients from healthy individuals. Kaplan-Meier survival and Cox regression were used to evaluate the potential predictive ability of serum miR-637 levels during follow-up for cerebral ischemia events. Serum miR-637 of CAS patients was significantly reduced which was a good indicator of severe carotid stenosis (P < 0.001). Reduced miR-637 can identify CAS patients from healthy individuals, demonstrating strong diagnostic capabilities. Furthermore, Kaplan-Meier analysis confirmed that the lower miR-637 levels in CAS, the more cerebral ischemia events (log-rank, P = 0.035), and the Multivariate Cox regressions confirmed that miR-637 was an independent predictor of CAS patients (HR = 0.073, 95%CI = 0.017-0.313, P < 0.001). We confirmed that serum miR-637 in CAS patients was significantly reduced. And reduced miR-637 was not only a potentially reliable biomarker for the diagnosis of CAS but also a useful indicator for predicting future cerebral ischemic events.

Serum Sphingosine-1-Phosphate Levels Are Associated With Severity and Outcome in Patients With Cerebral Ischemia.

BACKGROUND AND PURPOSE: The aim of this study was to examine whether sphingosine-1-phosphate (S1P) levels in patients with acute stroke are associated with stroke severity and outcome. METHODS: In a prospective stroke cohort (MARK-STROKE), 374 patients with acute ischemic stroke or transient ischemic attack were enrolled (mean age: 67.9±13.0 years, sex: 64.7% male), and serum-S1P at admission was analyzed with tandem mass spectrometry. In addition to cross-sectional analyses, 79 adverse events (death, stroke, myocardial infarction, rehospitalization) were recorded in 270 patients during follow-up. Regression analyses were adjusted for age, sex, low-density lipoprotein cholesterol, and vascular risk factors. Results were validated in an independent stroke cohort with 219 patients with acute ischemic stroke (CIRCULAS). RESULTS: Low serum-S1P was associated with higher National Institutes of Health Stroke Scale score at admission and with anterior circulation nonlacunar infarcts determined by multivariate regression analyses. During a follow-up of 294±170 days, patients with S1P in the lowest tertile (<1.33 µmol/L) had more adverse events (Kaplan-Meier analysis, P=0.048 for trend). In adjusted Cox regression analysis, the lowest S1P tertile was associated with a worse outcome after stroke (hazard ratio, HR 0.51 [95% confidence interval 0.28-0.92]). Results were confirmed in an independent cohort, ie, low S1P levels were associated with higher National Institutes of Health Stroke Scale, larger infarct volumes and worse outcome after 90 days (ß-coefficient: -0.03, P=0.026; ß-coefficient: -0.099, P=0.009 and odds ratio 0.52 [0.28-0.96], respectively). CONCLUSIONS: Our findings imply a detrimental role of low S1P levels in acute stroke and therefore underpin the therapeutic potential of S1P-mimics.

PaCO2-management in the neuro-critical care of patients with subarachnoid hemorrhage.

The partial pressure of carbon dioxide (PaCO2) in the arterial blood is a strong vasomodulator affecting cerebral blood flow and the risk of cerebral edema and ischemia after acute brain injury. In turn, both complications are related to poor outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). We aimed to analyze the effect of PaCO2 levels on the course and outcome of aSAH. All patients of a single institution treated for aSAH over 13.5 years were included (n = 633). Daily PaCO2 values from arterial blood gas measurements were recorded for up to 2 weeks after ictus. The study endpoints were: delayed cerebral ischemia (DCI), need for decompressive craniectomy due to increased intracranial pressure > 20 mmHg refractory to conservative treatment and poor outcome at 6-months follow-up (modified Rankin scale > 2). By correlations with the study endpoints, clinically relevant cutoffs for the 14-days mean values for the lowest and highest daily PaCO2 levels were defined by receiver operating characteristic curve analysis. Association with the study endpoints for the identifies subgroups was analyzed using multivariate analysis. The optimal range for PaCO2 values was identified between 30 and 38 mmHg. ASAH patients with poor initial condition (WFNS 4/5) were less likely to show PaCO2 values within the range of 30-38 mmHg (p < 0.001, OR = 0.44). In the multivariate analysis, PaCO2 values between 30 and 38 mmHg were associated with a lower risk for decompressive craniectomy (p = 0.042, aOR = 0.27), DCI occurrence (p = 0.035; aOR = 0.50), and poor patient outcome (p = 0.004; aOR = 0.42). The data from this study shows an independent positive association between low normal mean PaCO2 values during the acute phase of aSAH and patients' outcome. This effect might be attributed to the reduction of intracranial hypertension and alterations in the cerebral blood flow.

Diagnostic value of combined serological markers in the detection of acute cerebral infarction.

ABSTRACT: To evaluate the value of the combination schemes of 10 serological markers in the clinical diagnosis of acute cerebral infarction.The level of total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, homocysteine (HCY), lipoprotein-related phospholipase A2, ischemia-modified albumin, complement C1q, and lipoprotein a were analyzed in 154 patients with acute ischemic cerebral infarction. The optimized diagnostic combination for acute cerebral infarction was explored by calculating the maximum area under the receiver operating characteristic curves (AUC).The levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, HCY, lipoprotein-related phospholipase A2, ischemia-modified albumin, complement C1q, and lipoprotein a were significantly higher in the patient vs the control group. Moreover, the positive rate of HCY reached 89.9%. The analysis of the receiver operating characteristic curve of each index and their combinations showed that the minimum AUC of HDL-C alone was 0.543, while the maximum AUC of HCY was 0.853. A multiple logistic regression analysis indicated that HDL-C was a slightly significant variate in the diagnosis of acute cerebral infarction.The value of individual serological markers in the diagnosis of acute cerebral infarction was slightly significant, while the combination of the markers significantly improved the efficiency of its diagnosis.

sLOX-1: A Molecule for Evaluating the Prognosis of Recurrent Ischemic Stroke.

Several clinical parameters and biomarkers have been proposed as prognostic markers for stroke. However, it has not been clarified whether the risk factors affecting the prognosis of patients with recurrent and first-ever stroke are similar. In this study, we aimed to explore the relationship between soluble lectin-like oxidized low-density lipoprotein receptor 1 (sLOX-1) levels and the prediction of the functional outcome in patients with recurrent and first-ever stroke. A total of 266 patients with recurrent and first-ever stroke, who underwent follow-up for 3 months, were included in this study. Plasma samples were collected within 24 h after onset. The results showed that biomarkers for the prognosis of patients with recurrent stroke were different from that of those with first-ever stroke. sLOX-1 levels were correlated with modified Rankin Scale scores of patients with recurrent stroke alone (r = 0.3232, p = 0.001). sLOX-1 levels were also associated with an increased risk of unfavorable outcomes in patients with recurrent stroke with an adjusted odds ratio of 1.489 (95% confidence interval, 1.204-1.842, p < 0.0001). Combining the risk factors showed greater accuracy for prognosis, yielding a sensitivity of 93.2% and a specificity of 75%, with an area under the curve of 0.916, evaluated by the receiver operating characteristic curve. These findings suggest that the diagnosis and prognosis are different between patients with recurrent stroke and those with first-ever stroke, and sLOX-1 level is an independent prognostic marker in patients with recurrent stroke.

Dysregulation Serum miR-19a-3p is a Diagnostic Biomarker for Asymptomatic Carotid Artery Stenosis and a Promising Predictor of Cerebral Ischemia Events.

This study aims to identify the diagnostic potential of microRNA-19a-3p (miR-19a-3p) for asymptomatic carotid artery stenosis (CAS) and clinical predictive potential for cerebral ischemia events (CIEs). Serum samples from 101 asymptomatic CAS patients and 98 healthy controls were collected. And it was found that serum miR-19a-3p in asymptomatic CAS patients was generally elevated (P < .05). Increased miR-19a-3p in asymptomatic CAS was associated with severe CAS (odds ratio = 3.920, 95% confidence interval [CI] = 1.482-10.372, P < .01). The area under the receiver operating characteristic (ROC) curve (AUC) was 0.905, indicating that the level of miR-19a-3p was statistically significant for the diagnosis of asymptomatic CAS. Furthermore, the level of serum miR-19a-3p (hazard ratio [HR] = 8.507, 95% confidence interval [CI] = 2.239-32.328, P = .002) and degree of artery stenosis (HR = 3.695, 95% CI = 1.127-12.109, P = .031) were independent predictors of occurrence of CIE. Moreover, patients with elevated miR-19a-3p levels were more likely to experience CIE than patients with low levels. Upregulated miR-19a-3p can be used as a diagnostic biomarker for asymptomatic CAS patients and as an independent predictor of CIE.

Emerging agents for the treatment and prevention of stroke: progress in clinical trials.

INTRODUCTION: Recent years have witnessed unprecedented progress in stroke care, but unmet needs persist regarding the efficacy of acute treatment and secondary prevention. Novel approaches are being tested to enhance the efficacy of thrombolysis or provide neuroprotection in non-thrombolized patients. AREAS COVERED: The current review highlights pharmaceutical agents under evaluation in clinical trials concerning the acute, subacute, and chronic phase post-stroke. We examine the evidence in favor of tenecteplase as an alternative thrombolytic drug to alteplase, nerinetide as a promising neuroprotective agent, and glibenclamide for reducing edema in malignant hemispheric infarction. We discuss the use of ticagrelor and the promising novel category of factor XI inhibitors in the subacute phase after stroke. We offer our insights on combined rivaroxaban and antiplatelet therapy, PCSK-9 inhibitors, and other non-statin hypolipidemic agents, as well as novel antidiabetic agents that have been shown to reduce cardiovascular events in the long-term. EXPERT OPINION: Current approaches in stroke treatment and stroke prevention have already transformed stroke care from a linear one-for-all treatment paradigm to a more individualized approach that targets specific patient subgroups with novel pharmaceutical agents. This tendency enriches the therapeutic armamentarium with novel agents developed for specific stroke subgroups. ABBREVIATIONS: IVT: intravenous thrombolysis; RCTs: randomized-controlled clinical trials; TNK: Tenecteplase; COVID-19: Coronavirus 2019 Disease; EXTEND-IA TNK: The Tenecteplase versus Alteplase Before Endovascular Therapy for Ischemic Stroke trial; AIS: acute ischemic stroke; NNT: number needed to treat; MT: mechanical thrombectomy; sICH: symptomatic intracranial hemorrhage; mRS: modified Rankin Scale; AHA/ASA: American Heart Association/American Stroke Association; ESO: European Stroke Organization; NA-1: Nerinetide; ENACT: Evaluating Neuroprotection in Aneurysm Coiling Therapy; CTA: CT angiography; TIA: transient ischemic attack; CHANCE: Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events; LOF: loss-of-function; PRINCE: Platelet Reactivity in Acute Nondisabling Cerebrovascular Events; THALES: Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and ASA [acetylsalicylic acid] for Prevention of Stroke and Death; CHANCE-2: Clopidogrel With Aspirin in High-risk Patients With Acute Non-disabling Cerebrovascular Events II; FXI: Factor XI; PACIFIC-STROKE: Program of Anticoagulation via Inhibition of FXIa by the Oral Compound BAY 2433334-NonCardioembolic Stroke study; COMPASS: Cardiovascular Outcomes for People Using Anticoagulation Strategies; CANTOS-ICAD: Combination Antithrombotic Treatment for Prevention of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease; SAMMPRIS: Stenting and Aggressive Medical Therapy for Preventing Recurrent Stroke in Intracranial Stenosis; WASID: Warfarin-Aspirin Symptomatic Intracranial Disease; SPARCL: Stroke Prevention by Aggressive Reduction in Cholesterol Levels; LDL-C: low-density lipoprotein cholesterol; TST: Treat Stroke to Target; IMPROVE-IT: Improved Reduction of Outcomes: Vytorin Efficacy International Trial; PCSK9: proprotein convertase subtilisin-kexin type 9; FOURIER: Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk; CLEAR: Cholesterol Lowering via Bempedoic acid, an ACL-inhibiting Regimen; REDUCE-IT: Reduction of Cardiovascular Events With EPA Intervention Trial; STRENGTH: Outcomes Study to Assess STatin Residual Risk Reduction With EpaNova in HiGh CV Risk PatienTs With Hypertriglyceridemia; ACCORD: Action to Control Cardiovascular Risk in Diabetes; ADVANCE: Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; VADT: Veterans Affairs Diabetes Trial; GLP-1R: Glucagon-like peptide-1 receptor; SGLT2: sodium-glucose cotransporter 2; CONVINCE: COlchicine for preventioN of Vascular Inflammation in Non-CardioEmbolic stroke; PROBE: Prospective Randomized Open-label Blinded Endpoint assessment.