Prognostic performance of neutrophil/lymphocyte ratio and platelet/lymphocyte ratio for mortality in patients with acute stroke / Rendimiento pronóstico de la razón neutrófilos/linfocitos y la razón plaquetas/linfocitos para la mortalidad en pacientes con ictus agudo

Objective: 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. Design: Retrospective cohort study. Setting: Tertiary care hospital. Patients: Patients aged ≥18 years with a diagnosis of acute stroke and admitted to the hospital from May 2019 to June 2021. Interventions: None. Main variables of interests: Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and mortality. Results: 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. Conclusion: 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.(AU)

Objetivo: Evaluar el desempeño pronóstico de la relación neutrófilos-linfocitos (NLR) y la relación plaquetas-linfocitos (PLR) para la mortalidad en pacientes con stroke agudo tratados en un hospital peruano. Diseño: Estudio de cohorte retrospectivo. Ámbito: Hospital de atención terciaria. Participantes: Pacientes ≥18 años con diagnóstico de stroke agudo e ingresados en el hospital entre mayo de 2019 y junio de 2021. Intervenciones: Ninguna. Variables de interés principales: Razón neutrófilos/linfocitos, razón plaquetas/linfocitos y mortalidad. Resultados: Se incluyeron un total de 165 pacientes. La edad media fue de 66,1±14,2 años, y el 59,4% eran varones. Sólo el NLR tuvo un rendimiento superior a 0,7 (AUC: 0,75; IC95%: 0,65-0,85), y sus niveles elevados se asociaron con un mayor riesgo de mortalidad (RRa: 3,66; IC95%: 1,77-8,85) tras ajustar por factores de confusión. Conclusiones: La razón neutrófilos/linfocitos tiene un rendimiento pronóstico aceptable para la mortalidad en pacientes con stroke. Su uso puede ser considerado para estratificar el riesgo de los pacientes y considerar oportunamente cuidados y manejo alternativos.(AU)

Association of C-reactive protein level with adverse outcomes in patients with atrial fibrillation: A meta-analysis.

BACKGROUND: Studies on the association between C-reactive protein (CRP) level and poor outcomes have been yielded controversial results in patients with atrial fibrillation (AF). This meta-analysis sought to investigate the utility of elevated CRP level in predicting adverse outcomes in AF patients. METHODS: Two authors systematically searched PubMed and Embase databases (until December 10, 2022) for studies evaluating the value of elevated CRP level in predicting all-cause mortality, cardiovascular death, stroke, or major adverse cardiovascular events (MACEs) in AF patients. The predictive value of CRP was expressed by pooling adjusted hazard ratio (HR) with 95% confidence intervals (CI) for the highest versus the lowest level or per unit of log-transformed increase. RESULTS: Ten studies including 30,345 AF patients satisfied our inclusion criteria. For the highest versus the lowest CRP level, the pooled adjusted HR was 1.57 (95% CI 1.34-1.85) for all-cause mortality, 1.18 (95% CI 0.92-1.50) for cardiovascular death, and 1.57 (95% CI 1.10-2.24) for stroke, respectively. When analyzed the CRP level as continuous data, per unit of log-transformed increase was associated with a 27% higher risk of all-cause mortality (HR 1.27; 95% CI 1.23-1.32) and 16% higher risk of MACEs (HR 1.16; 95% CI 1.05-1.28). CONCLUSIONS: Elevated CRP level may be an independent predictor of all-cause mortality, stroke, and MACEs in patients with AF. CRP level at baseline can provide important prognostic information in risk classification of AF patients.

The association between circulating Hcy and Lp-PLA2 levels and poststroke depression: A meta-analysis.

OBJECTIVE: To analyze the correlation between circulating homocysteine (Hcy) and lipoprotein-associated phospholipase A2 (Lp-PLA2) levels and poststroke depression (PSD). MATERIALS AND METHODS: Chinese (Chinese National Knowledge Infrastructure, Wanfang, and VIP) and English (PubMed, EMBASE, MEDLINE, and Cochrane Library) databases on the correlation between circulating Hcy and Lp-PLA2 and PSD were collected. Meta-analysis was performed to compare the distinctions in circulating Hcy and Lp-PLA2 levels between PSD and non-PSD groups. Meta-analysis was conducted by using STATA 15.0 software. RESULTS: A total of 20 literatures were included in this study. The level of circulating Lp-PLA2 in the PSD group was obviously higher than that in the non-PSD group (weighted mean differences: 2.75, 95%CI: 0.10-5.39, P = .002), which was an independent predictor of PSD (effect size = 0.05, 95%CI: 0.03, 0.07, P < .001). The level of circulating Hcy in the PSD group was obviously higher than that in the non-PSD group (weighted mean differences = 1.41, 95%CI: 1.01, 1.81, P < .001), which was an independent influencing factor for the occurrence of PSD (effect size = 0.07, 95%CI: 0.04, 0.09, P = .011). CONCLUSION: Circulating Hcy and Lp-PLA2 levels are linked to the development of PSD, and can be applied as predictive or diagnostic indicators.

Changes in the triglyceride glucose-body mass index estimate the risk of stroke in middle-aged and older Chinese adults: a nationwide prospective cohort study.

BACKGROUND: Stroke was reported to be highly correlated with the triglyceride glucose-body mass index (TyG-BMI). Nevertheless, literature exploring the association between changes in the TyG-BMI and stroke incidence is scant, with most studies focusing on individual values of the TyG-BMI. We aimed to investigate whether changes in the TyG-BMI were associated with stroke incidence. METHODS: Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS), which is an ongoing nationally representative prospective cohort study. The exposures were changes in the TyG-BMI and cumulative TyG-BMI from 2012 to 2015. Changes in the TyG-BMI were classified using K-means clustering analysis, and the cumulative TyG-BMI was calculated as follows: (TyG-BMI2012 + TyG-BMI2015)/2 × time (2015-2012). Logistic regressions were used to determine the association between different TyG-BMI change classes and stroke incidence. Meanwhile, restricted cubic spline regression was applied to examine the potential nonlinear association of the cumulative TyG-BMI and stroke incidence. Weighted quantile sum regression was used to provide a comprehensive explanation of the TyG-BMI by calculating the weights of FBG, triglyceride-glucose (TG), and BMI. RESULTS: Of the 4583 participants (mean [SD] age at baseline, 58.68 [9.51] years), 2026 (44.9%) were men. During the 3 years of follow-up, 277 (6.0%) incident stroke cases were identified. After adjusting for potential confounders, compared to the participants with a consistently low TyG-BMI, the OR for a moderate TyG-BMI with a slow rising trend was 1.01 (95% CI 0.65-1.57), the OR for a high TyG-BMI with a slow rising trend was 1.62 (95% CI 1.11-2.32), and the OR for the highest TyG-BMI with a slow declining trend was 1.71 (95% CI 1.01-2.89). The association between the cumulative TyG-BMI and stroke risk was nonlinear (Passociation = 0.017; Pnonlinearity = 0.012). TG emerged as the primary contributor when the weights were assigned to the constituent elements of the TyG-BMI (weight2012 = 0.466; weight2015 = 0.530). CONCLUSIONS: Substantial changes in the TyG-BMI are independently associated with the risk of stroke in middle-aged and older adults. Monitoring long-term changes in the TyG-BMI may assist with the early identification of individuals at high risk of stroke.

Association of hemoglobin variability with the risk of cardiovascular disease: a nationally representative retrospective cohort study from South Korea.

Hemoglobin variability is known to increase cardiovascular mortality in chronic kidney disease, but the association of hemoglobin variability with the risk of cardiovascular disease (CVD) in the general population is yet unclear. This retrospective cohort study based on 'the South Korean National Health Insurance Service database' consisted of 198,347 adults who went through all three health examinations. Hemoglobin variability is defined as the average successive variability of three separate hemoglobin values from each health screening period. Participants were followed up for 6 years to determine the risk of coronary heart disease and stroke. We used multivariate Cox proportional hazards regression to examine the adjusted hazard ratios for CVD according to hemoglobin variability. Per 1 unit increase of hemoglobin variability, the risk for CVD (aHR 1.06, 95% CI 1.02-1.09) and stroke (aHR 1.08, 95% CI 1.03-1.13) increased significantly. The risk-increasing trend was preserved in the low-to-moderate risk group of CVDs (aHR 1.07, 95% CI 1.02-1.11). This result suggests that subjects with high hemoglobin variability who would otherwise be categorized as having low-to-moderate CVD risk may have higher risk of CVD than those with low hemoglobin variability.

A mathematical framework for the dynamic interaction of pulsatile blood, brain, and cerebrospinal fluid.

BACKGROUND: Shedding light on less-known aspects of intracranial fluid dynamics may be helpful to understand the hydrocephalus mechanism. The present study suggests a mathematical framework based on in vivo inputs to compare the dynamic interaction of pulsatile blood, brain, and cerebrospinal fluid (CSF) between the healthy subject and the hydrocephalus patient. METHOD: The input data for the mathematical formulations was pulsatile blood velocity, which was measured using cine PC-MRI. Tube law was used to transfer the created deformation by blood pulsation in the vessel circumference to the brain domain. The pulsatile deformation of brain tissue with respect to time was calculated and considered to be inlet velocity in the CSF domain. The governing equations in all three domains were continuity, Navier-Stokes, and concentration. We used Darcy law with defined permeability and diffusivity values to define the material properties in the brain. RESULTS: We validated the preciseness of the CSF velocity and pressure through the mathematical formulations with cine PC-MRI velocity, experimental ICP, and FSI simulated velocity and pressure. We used the analysis of dimensionless numbers including Reynolds, Womersley, Hartmann, and Peclet to evaluate the characteristics of the intracranial fluid flow. In the mid-systole phase of a cardiac cycle, CSF velocity had the maximum value and CSF pressure had the minimum value. The maximum and amplitude of CSF pressure, as well as CSF stroke volume, were calculated and compared between the healthy subject and the hydrocephalus patient. CONCLUSION: The present in vivo-based mathematical framework has the potential to gain insight into the less-known points in the physiological function of intracranial fluid dynamics and the hydrocephalus mechanism.

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.

Liver vitronectin release into the bloodstream increases due to reduced vagal muscarinic signaling after cerebral stroke in female mice.

Vitronectin (VTN) is a glycoprotein enriched in the blood and activates integrin receptors. VTN blood levels increase only in female mice 24 h after an ischemic stroke and exacerbate brain injury through IL-6-driven inflammation, but the VTN induction mechanism is unknown. Here, a 30 min middle cerebral artery occlusion (MCAO) in female mice induced VTN protein in the liver (normally the main source) in concert with plasma VTN. Male mice were excluded as VTN is not induced after stroke. MCAO also increased plasma VTN levels after de novo expression of VTN in the liver of VTN-/- female mice, using a hepatocyte-specific (SERPINA1) promoter. MCAO did not affect SERPINA1 or VTN mRNA in the liver, brain, or several peripheral organs, or platelet VTN, compared to sham mice. Thus, hepatocytes are the source of stroke-induced increases in plasma VTN, which is independent of transcription. The cholinergic innervation by the parasympathetic vagus nerve is a potential source of brain-liver signaling after stroke. Right-sided vagotomy at the cervical level led to increased plasma VTN levels, suggesting that VTN release is inhibited by vagal tone. Co-culture of hepatocytes with cholinergic neurons or treatment with acetylcholine, but not noradrenaline (sympathetic transmitter), suppressed VTN expression. Hepatocytes have muscarinic receptors and the M1/M3 agonist bethanechol decreased VTN mRNA and protein release in vitro via M1 receptors. Finally, systemic bethanechol treatment blocked stroke-induced plasma VTN. Thus, VTN translation and release are inhibited by muscarinic signaling from the vagus nerve and presents a novel target for lessening detrimental VTN expression.

Plasma lipoprotein-associated phospholipase A2 is associated with acute ischemic stroke in patients with atrial fibrillation.

OBJECTIVE: To investigate the association between lipoprotein-associated phospholipase A2 (Lp-PLA2) concentration and the incidence of acute ischemic stroke (AIS) in patients with atrial fibrillation (AF). METHODS: A total of 257 patients admitted to the Kaifeng Central Hospital were enrolled in this study. Receiver operating characteristic (ROC) curve analysis and multivariate logistic regression analysis were used to determine the association between Lp-PLA2 and AIS in patients with AF. RESULTS: In AF group, plasma Lp-PLA2 concentrations were significantly higher in patients with AIS than in those without it (277.4 vs 155.1, p < 0.001). And in the group of AIS patients, patients with AF also had a significantly higher level of Lp-PLA2 concentration than those without (277.4 vs 204.2, p < 0.001). The analysis of the ROC curve showed a significant diagnostic value of Lp-PLA2 for the incidence of AIS in patients with AF (AUC = 0.840, 95% CI: 0.737-0.871, p < 0.001), and the optimal cut-off point was 220.5 ng/ml, with a sensitivity and specificity of 82.14% and 75.5%, respectively. All AF patients were divided into two subgroups: the high Lp-PLA2 group (≥220.5 ng/ml) and the low Lp-PLA2 group (<220.5 ng/ml). And multivariate logistic regression analysis showed that after adjustment of confounders, Lp-PLA2 (OR 12.48, 95%CI 5.73-27.16, p < 0.001) was independently associated with the incidence of AIS in patients with AF. CONCLUSIONS: Plasma Lp-PLA2 concentration was independently associated with the development of AIS in patients with AF. Lp-PLA2 is a potential biomarker for stratification of risk for AIS in patients with AF.

Kitchen Diet vs. Industrial Diets-Impact on Intestinal Barrier Parameters among Stroke Patients.

BACKGROUND AND AIMS: Strokes are the second highest cause of death in the world and the most common cause of permanent disability in adults. Intestinal barrier permeability thus contributes to diminished homeostasis within the body, which further affects the healing process and convalescence. Each stroke patient should be administered with ingredients that support the intestinal barrier (e.g., protein and fiber). The aim of this study was to compare the effect of various types of diet (enteral with or without fiber vs. a mixed kitchen diet) on the metabolic activity of intestinal microbiota, namely short chain fatty acids, and gut barrier integrity parameters (zonulin and calprotectin. METHODS: Patients (n = 59), after suffering an ischemic stroke, were randomly allocated to three groups receiving: the kitchen diet (n = 32; 1.2 g fiber in 100 mL); Nutrison Energy® (n = 14; 0.02 g fiber in 100 mL); and Nutrison Diason Energy HP® (n = 13; 1.8 g fiber in 100 mL). The patients underwent anthropometric measurements and blood samples (for prealbumin measurements), and stool samples (for zonulin and calprotectin determinations) were taken twice, on admission and a week later. RESULTS: Industrial diets enriched with fiber maintained nutritional status and had a beneficial effect on intestinal barrier permeability parameters. Patients fed with kitchen diets demonstrated a decreased number of lymphocytes, hemoglobin, erythrocytes, and increased serum concentration of C-reactive protein, but improved gut barrier markers. Proton pump inhibitors were shown to increase the inflammatory process in gut. CONCLUSIONS: Stroke patients should be administered with industrial diets enriched with fiber to improve gut barrier integrity and nutritional parameters.

Monocyte subsets, T cell activation profiles, and stroke in men and women: The Multi-Ethnic Study of Atherosclerosis and Cardiovascular Health Study.

BACKGROUND AND AIMS: Despite mechanistic data implicating unresolving inflammation in stroke pathogenesis, data regarding circulating immune cell phenotypes - key determinants of inflammation propagation versus resolution - and incident stroke are lacking. Therefore, we aimed to comprehensively define associations of circulating immune phenotypes and activation profiles with incident stroke. METHODS: We investigated circulating leukocyte phenotypes and activation profiles with incident adjudicated stroke in 2104 diverse adults from the Multi-Ethnic Study of Atherosclerosis (MESA) followed over a median of 16.6 years. Cryopreserved cells from the MESA baseline examination were thawed and myeloid and lymphoid lineage cell subsets were measured using polychromatic flow cytometry and intracellular cytokine activation staining. We analyzed multivariable-adjusted associations of cell phenotypes, as a proportion of parent cell subsets, with incident stroke (overall) and ischemic stroke using Cox regression models. RESULTS: We observed associations of intermediate monocytes, early-activated CD4+ T cells, and both CD4+ and CD8+ T cells producing interleukin-4 after cytokine stimulation (Th2 and Tc2, respectively) with higher risk for incident stroke; effect sizes ranged from 35% to 62% relative increases in risk for stroke. Meanwhile, differentiated and memory T cell phenotypes were associated with lower risk for incident stroke. In sex-stratified analyses, positive and negative associations were especially strong among men but null among women. CONCLUSIONS: Circulating IL-4 producing T cells and intermediate monocytes were significantly associated with incident stroke over nearly two decades of follow-up. These associations were stronger among men and not among women. Further translational studies are warranted to define more precise targets for prognosis and intervention.

The Use of Lipoprotein-Associated Phospholipase A2 in a Chinese Population to Predict Cardiovascular Events.

Objective: To explore associations between lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cardiovascular events in a Chinese population, with a long-term follow-up. Methods: A random sample of 2,031 participants (73.6% males, mean age = 60.4 years) was derived from the Asymptomatic Polyvascular Abnormalities Community study (APAC) from 2010 to 2011. Serum Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay (ELISA). The composite endpoint was a combination of first-ever stroke, myocardial infarction (MI) or all-cause death. Lp-PLA2 associations with outcomes were assessed using Cox models. Results: The median Lp-PLA2 level was 141.0 ng/mL. Over a median follow-up of 9.1 years, we identified 389 events (19.2%), including 137 stroke incidents, 43 MIs, and 244 all-cause deaths. Using multivariate Cox regression, when compared with the lowest Lp-PLA2 quartile, the hazard ratios with 95% confidence intervals for developing composite endpoints, stroke, major adverse cardiovascular events, and all-cause death were 1.77 (1.24-2.54), 1.92 (1.03-3.60), 1.69 (1.003-2.84), and 1.94 (1.18-3.18) in the highest quartile, respectively. Composite endpoints in 145 (28.6%) patients occurred in the highest quartile where Lp-PLA2 (159.0 ng/mL) was much lower than the American Association of Clinical Endocrinologists recommended cut-off point, 200 ng/mL. Conclusion: Higher Lp-PLA2 levels were associated with an increased risk of cardiovascular event/death in a middle-aged Chinese population. The Lp-PLA2 cut-off point may be lower in the Chinese population when predicting cardiovascular events.

The Impact of Sex and Gender on Stroke.

Women face a disproportionate burden of stroke mortality and disability. Biologic sex and sociocultural gender both contribute to differences in stroke risk factors, assessment, treatment, and outcomes. There are substantial differences in the strength of association of stroke risk factors, as well as female-specific risk factors. Moreover, there are differences in presentation, response to treatment, and stroke outcomes in women. This review outlines current knowledge of impact of sex and gender on stroke, as well as delineates research gaps and areas for future inquiry.

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.

Red Blood Cell Morphodynamics in Patients with Polycythemia Vera and Stroke.

Polycythemia vera (PV) is a Ph-negative myeloproliferative neoplasm (MPN) which is characterized by erythrocytosis and a high incidence of thrombotic complications, including stroke. The study aimed to evaluate red blood cell (RBC) morphodynamic properties in PV patients and their possible association with stroke. We enrolled 48 patients with PV in this cross-sectional study, 13 of which have a history of ischemic stroke. The control group consisted of 90 healthy subjects. RBC deformability and aggregation analysis were performed using a laser-assisted optical rotational red cell analyzer. The following parameters were calculated: aggregation amplitude (Amp), RBC rouleaux formation time constant (Tf), time of formation of three-dimensional aggregates (Ts), aggregation index (AI), rate of complete disaggregation (y-dis), and the maximal elongation of RBC (EImax). Statistical analysis was performed with the R programming language. There were significant differences in RBCs morphodynamics features between patients with PV and the control group. Lower EImax (0.47 (0.44; 0.51) vs. 0.51 (0.47; 0.54), p < 0.001) and γ-dis (100 (100; 140) vs. 140 (106; 188) s-1, p < 0.001) along with higher amplitude (10.1 (8.6; 12.2) vs. 7.7 (6.6; 9.2), p < 0.001) was seen in patients with PV compared with control. A statistically significant difference between PV patients with and without stroke in aggregation amplitude was found (p = 0.03). A logistic regression model for stroke was built based on RBC morphodynamics which performed reasonably well (p = 0.01). RBC alterations may be associated with overt cerebrovascular disease in PV, suggesting a possible link between erythrocyte morphodynamics and increased risk of stroke.

Relationship between adiponectin multimer levels and subtypes of cerebral infarction.

AIM: Serum adiponectin levels are decreased in patients with cerebral infarction. Adiponectin in circulation exists in three isoforms: high molecular weight (HMW), medium molecular weight (MMW), and low molecular weight (LMW) adiponectin. We measured serum levels of total adiponectin and adiponectin multimers (HMW, MMW, and LMW) in patients with cerebral infarction and compared the serum levels of the three adiponectin multimers in stroke subtypes. We also evaluated the clinical value of adiponectin multimer levels as a biomarker for cerebral infarction. METHODS: We assessed a total of 132 patients with cerebral infarctions. The serum levels of total and adiponectin multimers were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: The total and HMW adiponectin levels were significantly lower in atherothrombotic infarction (AI) than in cerebral embolism (CE) (total, p < 0.05; HMW, p < 0.05). In male patients, the MMW adiponectin level was significantly lower in the lacunar infarction (LI) group than in the AI group (p < 0.05). The LMW adiponectin level was significantly lower in the AI group than in the LI and CE groups (LI, p < 0.001; CE, p = 0.001). However, there were no significant differences in adiponectin multimer levels among the stroke subtypes in female subjects. Additionally, in female patients with AI and LI, the LMW adiponectin levels were negatively associated with C-reactive protein (CRP; AI, p < 0.05; LI, p < 0.05). CONCLUSION: These findings suggest that a decrease in adiponectin is associated with AI and that serum LMW adiponectin level represents a potential biomarker for AI.

Evidence of plasma biomarkers indicating high risk of dementia in cognitively normal subjects.

Subjects with comorbidities are at risk for neurodegeneration. There is a lack of a direct relationship between comorbidities and neurodegeneration. In this study, immunomagnetic reduction (IMR) assays were utilized to assay plasma Aß1-42 and total tau protein (T-Tau) levels in poststroke (PS, n = 27), family history of Alzheimer's disease (ADFH, n = 35), diabetes (n = 21), end-stage renal disease (ESRD, n = 41), obstructive sleep apnea (OSA, n = 20), Alzheimer's disease (AD, n = 65). Thirty-seven healthy controls (HCs) were enrolled. The measured concentrations of plasma Aß1-42 were 14.26 ± 1.42, 15.43 ± 1.76, 15.52 ± 1.60, 16.15 ± 1.05, 16.52 ± 0.59, 15.97 ± 0.54 and 20.06 ± 3.09 pg/mL in HC, PS, ADFH, diabetes, ESRD, OSA and AD groups, respectively. The corresponding concentrations of plasma T-Tau were 15.13 ± 3.62, 19.29 ± 8.01, 17.93 ± 6.26, 19.74 ± 2.92, 21.54 ± 2.72, 20.17 ± 2.77 and 41.24 ± 14.64 pg/mL. The plasma levels of Aß1-42 and T-Tau in were significantly higher in the PS, ADFH, diabetes, ESRD and OSA groups than controls (Aß1-42 in PS: 15.43 ± 1.76 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.005; T-Tau in PS: 19.29 ± 8.01 vs. 15.13 ± 3.62 pg/mL, p < 0.005, Aß1-42 in ADFH: 15.52 ± 1.60 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in ADFH: 17.93 ± 6.26 vs. 15.13 ± 3.62 pg/mL, p < 0.005, Aß1-42 in diabetes: 16.15 ± 1.05 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in diabetes: 19.74 ± 2.92 vs. 15.13 ± 3.62 pg/mL, p < 0.001, Aß1-42 in ESRD: 16.52 ± 0.59 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in ESRD: 21.54 ± 2.72 vs. 15.13 ± 3.62 pg/mL, p < 0.001, Aß1-42 in OSA: 15.97 ± 0.54 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in OSA: 20.17 ± 2.77 vs. 15.13 ± 3.62 pg/mL, p < 0.001). This evidence indicates the high risk for dementia in these groups from the perspective of plasma biomarkers.

Potential Biomarkers for Post-Stroke Cognitive Impairment: A Systematic Review and Meta-Analysis.

Stroke is a primary debilitating disease in adults, occurring in 15 million individuals each year and causing high mortality and disability rates. The latest estimate revealed that stroke is currently the second leading cause of death worldwide. Post-stroke cognitive impairment (PSCI), one of the major complications after stroke, is frequently underdiagnosed. However, stroke has been reported to increase the risk of cognitive impairment by at least five to eight times. In recent decades, peripheral blood molecular biomarkers for stroke have emerged as diagnostic, prognostic, and therapeutic targets. In this study, we aimed to evaluate some blood-derived proteins for stroke, especially related to brain damage and cognitive impairments, by conducting a systematic review and meta-analysis and discussing the possibility of these proteins as biomarkers for PSCI. Articles published before 26 July 2021 were searched in PubMed, Embase, the Web of Science, and the Cochrane Library to identify all relevant studies reporting blood biomarkers in patients with stroke. Among 1820 articles, 40 were finally identified for this study. We meta-analyzed eight peripheral biomarker candidates: homocysteine (Hcy), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), uric acid, and glycated hemoglobin (HbA1c). The Hcy, CRP, TC, and LDL-C levels were significantly higher in patients with PSCI than in the non-PSCI group; however, the HDL-C, TG, uric acid, and HbA1c levels were not different between the two groups. Based on our findings, we suggest the Hcy, CRP, TC, and LDL-C as possible biomarkers in patients with post-stroke cognitive impairment. Thus, certain blood proteins could be suggested as effective biomarkers for PSCI.