Leukocyte Counts and Ratios Are Predictive of Stroke Outcome and Hemorrhagic Complications Independently of Infections.
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ABSTRACT:
SUBMITTER: Semerano A
PROVIDER: S-EPMC7145963 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPerinatal hemorrhagic stroke in late preterm and term neonates is understudied. We describe two-month and two-year neurological outcomes in a prospective cohort.MethodsNeonates ≥36 weeks' gestation with spontaneous hemorrhagic stroke (parenchymal and intraventricular) presenting at age ≤28 days were enrolled between March 2007 and May 2015 at three tertiary pediatric centers. Hemorrhagic transformation of arterial ischemic stroke or cerebral sinovenous thrombosis was excluded. The Pediatric Stroke Outcome Measure (PSOM) assessed outcomes. Wilcoxon signed-rank tests evaluated change over time.ResultsTwenty-six neonates were included (median age: 1 day, interquartile range [IQR] 0 to 16; median gestational age: 38.3 weeks, IQR 37.0 to 39.0). Hemorrhage was isolated intraventricular in seven (27%), isolated intraparenchymal in six (23%), and a combination in 10 (39%). Three neonates (12%) died during hospitalization; one died later due to cardiac disease. Among 22 survivors, outcomes were assessed at a median of 2.1 months (IQR 1.7 to 3.3) in 96% and 1.9 years (IQR 1.3 to 2.0) in 73%. Median PSOM scores were 0.0 (IQR 0.0 to 1.0) and 0.25 (IQR 0.0 to 1.3), respectively. At two years, 45% of patients had no or nonimpairing deficits (PSOM <1.0), 30% had mild deficits (PSOM 1.0 to 2.0), and 5% had moderate deficits (PSOM 2.5 to 4.5). Over time, 31% worsened and 6% improved. Although total PSOM scores did not change significantly (P = 0.08), language subscores worsened (P = 0.009). No child developed epilepsy.ConclusionsPerinatal hemorrhagic stroke survivors had favorable outcomes in early childhood; at two years moderate to severe deficits occurred in 5%. Language deficits may emerge over time, warranting close follow-up.
| S-EPMC7071982 | biostudies-literature
Project description:BackgroundNeuroinflammation plays an important role in the pathogenesis of acute ischemic stroke (AIS) and peripheral leukocyte counts have proved to be independent predictors of stroke severity and outcomes. Clinical significance of large vessel occlusion (LVO) in AIS is increasing, as these patients are potential candidates for endovascular thrombectomy and likely to have worse outcomes if not treated urgently. The aim of our study was to assess the relationship between on admission leukocyte counts and the presence of LVO in the early phase of AIS.MethodsWe have conducted a cross-sectional, observational study based on a registry of consecutive AIS patients admitted up to 4.5 h after stroke onset. Blood samples were taken at admission and leukocyte counts were measured immediately. The presence of LVO was verified based on the computed tomography angiography scan on admission.ResultsTotal white blood cell (WBC) and neutrophil counts were significantly higher in patients with LVO than those without LVO (P < 0.001 respectively). After adjustment for potential confounders total WBC counts (adjusted OR: 1.405 per 1 × 109/L increase, 95% CI: 1.209 to 1.632) and neutrophil counts (adjusted OR: 1.344 per 1 × 109/L increase, 95% CI: 1.155 to 1.564) were found to have the strongest associations with the presence of LVO. Total WBC and neutrophil counts had moderate ability to discriminate an LVO in AIS (AUC: 0.667 and 0.655 respectively). No differences were recorded in leukocyte counts according to the size of the occluded vessel and the status of collateral circulation in the anterior vascular territory. However, total WBC and neutrophil counts tended to be higher in patients with LVO in the posterior circulation (p = 0.005 and 0.010 respectively).ConclusionHigher admission total WBC and neutrophil counts are strongly associated with the presence of LVO and has moderate ability to discriminate an LVO in AIS. Detailed evaluation of stroke-evoked inflammatory mechanisms and changes according to the presence of LVO demands further investigation.
| S-EPMC7716438 | biostudies-literature
Project description:Growing evidence suggests that stroke alters the phenotype of the peripheral immune system; better characterization of this response could provide new insights into stroke pathophysiology. In this investigation, we employed a deconvolution approach to informatically infer the cellular composition of the circulating leukocyte pool at multiple timepoints following stroke onset based on whole blood mRNA expression. Microarray data generated from the peripheral blood of 23 cardiovascular disease controls and 23 ischemic stroke patients at 3, 5, and 24 hours post-symptom onset were obtained from a public repository. Transcriptomic deconvolution was used to estimate the relative counts of nine leukocyte populations based on the expression of cell-specific transcripts, and cell counts were compared between groups across timepoints. Inferred counts of lymphoid cell populations including B-cells, CD4+ T-cells, CD8+ T-cells, ?? T-cells, and NK-cells were significantly lower in stroke samples relative to control samples. With respect to myeloid cell populations, inferred counts of neutrophils and monocytes were significantly higher in stroke samples compared to control samples, however inferred counts of eosinophils and dendritic cells were significantly lower. These collective differences were most dramatic in samples collected at 5 and 24 hours post-symptom onset. Findings were subsequently confirmed in a second dataset generated from an independent population of 24 controls and 39 ischemic stroke patients. Collectively, these results offer a comprehensive picture of the early stroke-induced changes to the complexion of the circulating leukocyte pool, and provide some of the first evidence that stroke triggers an acute decrease in eosinophil counts.
| S-EPMC6294043 | biostudies-literature
Project description:BackgroundChordoma pathogenesis remains poorly understood. In this study, we aimed to evaluate the relationships between microRNA-155 (miR-155) expression and the clinicopathological features of chordoma patients, and to evaluate the functional role of miR-155 in chordoma.MethodsThe miRNA expression profiles were analyzed using miRNA microarray assays. Regulatory activity of miR-155 was assessed using bioinformatic tools. miR-155 expression levels were validated by reverse transcription-polymerase chain reaction. The relationships between miR-155 expression and the clinicopathological features of chordoma patients were analyzed. Proliferative, migratory and invasive activities were assessed by MTT, wound healing, and Matrigel invasion assays, respectively.ResultsThe miRNA microarray assay revealed miR-155 to be highly expressed and biologically active in chordoma. miR-155 expression in chordoma tissues was significantly elevated, and this expression correlated significantly with disease stage (p = 0.036) and the presence of metastasis (p = 0.035). miR-155 expression also correlated significantly with poor outcomes for chordoma patients (hazard ratio, 5.32; p = 0.045). Inhibition of miR-155 expression suppressed proliferation, and the migratory and invasive activities of chordoma cells.ConclusionsWe have shown miR-155 expression to independently affect prognosis in chordoma. These results collectively indicate that miR-155 expression may serve not only as a prognostic marker, but also as a potential therapeutic target in chordoma.
| S-EPMC4496207 | biostudies-literature
Project description:ObjectiveST2 is a member of the toll-like receptor superfamily that can alter inflammatory signaling of helper T-cells. We investigated whether soluble ST2 (sST2) could independently predict outcome and hemorrhagic transformation (HT) in the setting of stroke.MethodsWe measured sST2 in patients enrolled in the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) network biomarker study. 646 patients had plasma samples collected at the time of hospital admission and 210 patients had a second sample collected 48 h after stroke onset. Functional outcome was assessed using the modified Rankin Scale (mRS), with good and poor outcomes defined as mRS 0-2 and 3-6, respectively. HT was classified using ECASS criteria. The relationships between sST2, outcome, and HT were evaluated using multivariable logistic regression, Kaplan-Meier survival analysis and receiver operating characteristic curves.Results646 patients were included in the analysis (mean age 69 years; 44% women), with a median NIHSS of 5 [IQR: 2-12]. The median sST2 level on hospital admission was 35.0 ng/mL [IQR: 25.7-49.8 ng/mL] and at 48 h it was 37.4 ng/mL [IQR 27.9-55.6 ng/mL]. sST2 was independently associated with poor outcome (OR: 2.77, 95% CI: 1.54-5.06; P = 0.003) and mortality (OR: 3.56, 95% CI: 1.58-8.38, P = 0.001) after multivariable adjustment. Plasma sST2 was also associated with hemorrhagic transformation after adjustment for traditional risk factors (OR: 5.58, 95% CI: 1.40-37.44, P = 0.039).InterpretationSoluble ST2 may serve as a prognostic biomarker for outcome and hemorrhagic transformation in patients with acute stroke. ST2 may link neuroinflammation and secondary injury after stroke.
| S-EPMC5553222 | biostudies-literature
Project description:Our group recently identified a panel of ten genes whose RNA expression levels in whole blood have utility for detection of stroke. The purpose of this study was to determine the mechanisms by which these genes become differentially expressed during stroke pathology. First, we assessed the transcriptional distribution of the ten genes across the peripheral immune system by measuring their expression levels on isolated neutrophils, monocytes, B-lymphocytes, CD-4+ T-lymphocytes, CD-8+ T-lymphocytes, and NK-cells generated from the blood of healthy donors (n?=?3). Then, we examined the relationship between the whole-blood expression levels of the ten genes and white blood cell counts in a cohort of acute ischemic stroke patients (n?=?36) and acute stroke mimics (n?=?15) recruited at emergency department admission. All ten genes displayed strong patterns of lineage-specific expression in our analysis of isolated leukocytes, and their whole-blood expression levels were correlated with white blood cell differential across the total patient population, suggesting that many of them are likely differentially expressed in whole blood during stroke as an artifact of stroke-induced shifts in leukocyte counts. Specifically, factor analysis inferred that over 50% of the collective variance in their whole-blood expression levels across the patient population was driven by underlying variance in white blood cell counts alone. However, the cumulative expression levels of the ten genes displayed a superior ability to discriminate between stroke patients and stroke mimics relative to white blood cell differential, suggesting that additional less prominent factors influence their expression levels which add to their diagnostic utility. These findings not only provide insight regarding this particular panel of ten genes, but also into the results of prior stroke transcriptomics studies performed in whole blood.
| S-EPMC6141354 | biostudies-literature
Project description:Hyperthermia is a predictor of poor outcome in ischemic (IS) and intracerebral hemorrhagic (ICH) stroke. Our aim was to study the plausible mechanisms involved in the poor outcome associated to hyperthermia in stroke. We conducted a case-control study including patients with IS (n = 100) and ICH (n = 100) within the first 12 hours from symptom onset. Specifically, IS and ICH patients were consecutively included into 2 subgroups, according to the highest body temperature within the first 24 hours: Tmax <37.5°C and Tmax ≥37.5°C, up to reach 50 patients per subgroup of temperature for both IS and ICH patients. Body temperature was determined at admission and every 4 hours during the first 48 hours. Main outcome variable was poor functional outcome (modified Rankin scale score >2) at 3 months. Serum levels of glutamate and active MMP-9 were measured at admission. Our results showed that Tmax ≥37.5°C within the first 24 hours was independently associated with poor outcome in both IS (OR, 12.43; 95% CI, 3.73-41.48; p<0.0001) and ICH (OR, 4.29; 95% CI, 1.32-13.91; p = 0.015) after adjusting for variables with a proven biological relevance for outcome. However, when molecular markers levels were included in the logistic regression model, we observed that glutamate (OR, 1.01; 95% CI, 1.00-1.02; p = 0.001) and infarct volume (OR, 1.06; 95% CI, 1.01-1.10; p = 0.015) were the only variables independently associated to poor outcome in IS, and active MMP-9 (OR, 1.04; 95% CI, 1.00-1.08; p = 0.002) and National Institute of Health Stroke Scale (NIHSS) at admission (OR, 1.29; 95% CI, 1.13-1.49; p<0.0001) in ICH. In conclusion, these results suggest that although the outcome associated to hyperthermia is similar in human IS and ICH, the underlying mechanisms may be different.
| S-EPMC3817202 | biostudies-other
Project description:ImportanceEmerging evidence implicates a role for neuroinflammation in Alzheimer disease (AD) pathogenesis, predominantly involving the innate immune system. Blood leukocyte counts are easily accessible markers of immune function; however, their association with the risk of AD is unknown.ObjectiveTo investigate the observational and genetic associations between types of blood leukocytes and risk of AD.Design, setting, and participantsIn a cohort study comprising observational and genetic analyses, the Copenhagen General Population Study prospective cohort (n = 101 582) was used for the observational analyses. For the genetic studies, nonlinearity was first evaluated for the association between leukocyte cell counts and AD risk using individual-level data from the UK Biobank (n = 365 913). Subsequently, a 2-sample mendelian randomization framework was applied using genetic instruments for blood leukocyte counts (n = 563 085); for AD, the European Alzheimer & Dementia Biobank was used, including 85 934 individuals with AD and 401 577 controls and the International Genomics of Alzheimer's Project, including 21 982 individuals with AD and 41 944 controls.ExposuresObservational and genetically determined types of blood leukocyte counts.Main outcomes and measuresHazard ratios (HRs) and 95% CIs for AD of cell count percentile groups in observational studies and odds ratios (ORs) and 95% CIs for AD per 1 SD genetically determined cell counts.ResultsThis cohort study included 101 582 participants (55 891 [55.0%] women) with a median age of 58 years (IQR, 48-67 years); of these, 1588 individuals developed AD. Multivariable-adjusted HRs for participants in the less than 5th vs the 25th to 75th (reference) percentile group were 1.24 (95% CI, 0.99-1.54) for blood monocytes and 1.25 for blood eosinophils (95% CI, 1.05-1.50). For participants in the greater than 95th vs the 25th to 75th percentile group, the HR was 1.30 (95% CI, 1.06-1.61) for blood neutrophils. Genetically, no evidence favored possible nonlinear associations. The ORs for AD per 1-SD decrease in genetically determined blood monocytes were 1.04 (95% CI, 1.00-1.10) in the European Alzheimer & Dementia Biobank consortium and 1.09 (95% CI, 1.01-1.17) in the International Genomics of Alzheimer's Project consortium. Using mendelian randomization, sensitivity analyses and multivariable analysis showed similar results.Conclusions and relevanceThe findings of this study suggest that low blood monocyte counts are associated with increased AD risk. These findings highlight a potential role of the innate immune system in AD pathogenesis.
| S-EPMC9552891 | biostudies-literature
Project description:The rapid increase in the incidence of multidrug-resistant infections today has led to enormous interest in antimicrobial peptides (AMPs) as suitable compounds for developing unusual antibiotics. In this study, clavanin A, an antimicrobial peptide previously isolated from the marine tunicate Styela clava, was selected as a purposeful molecule that could be used in controlling infection and further synthesized. Clavanin A was in vitro evaluated against Staphylococcus aureus and Escherichia coli as well as toward L929 mouse fibroblasts and skin primary cells (SPCs). Moreover, this peptide was challenged here in an in vivo wound and sepsis model, and the immune response was also analyzed. Despite displaying clear in vitro antimicrobial activity toward Gram-positive and -negative bacteria, clavanin A showed no cytotoxic activities against mammalian cells, and in acute toxicity tests, no adverse reaction was observed at any of the concentrations. Moreover, clavanin A significantly reduced the S. aureus CFU in an experimental wound model. This peptide also reduced the mortality of mice infected with E. coli and S. aureus by 80% compared with that of control animals (treated with phosphate-buffered saline [PBS]): these data suggest that clavanin A prevents the start of sepsis and thereby reduces mortality. These data suggest that clavanin A is an AMP that could improve the development of novel peptide-based strategies for the treatment of wound and sepsis infections.
| S-EPMC4325816 | biostudies-literature
Project description:Stroke is the second leading cause of long-term disability and death worldwide. Diabetes and hyperglycemia may impact the outcome of stroke. We examined the impact of hyperglycemia and diabetes on in-hospital death among ischemic and hemorrhagic stroke patients.Data from 766 consecutive patients with ischemic (83.15%) and hemorrhagic stroke were analyzed. Patients were classified into four groups: ischemic and diabetic; ischemic and non-diabetic; hemorrhagic and diabetic; and hemorrhagic and non-diabetic. Serum glucose was measured on admission at the emergency department together with biochemical and clinical parameters.Mean admission glucose in ischemic stroke patients with diabetes was higher than in non-diabetic ones (p < 0.001) and in hemorrhagic stroke patients with diabetes than in those without diabetes (p < 0.05). Mean admission glucose in all patients who died was significantly higher than in patients who survived. In multivariate analysis, the risk factors for outcome in patients with ischemic stroke and without diabetes were age, admission glucose level and estimated glomerular filtration rate (eGFR), while in diabetics they were female gender, admission glucose level, and eGFR; in patients with hemorrhagic stroke and without diabetes they were age and admission glucose levels. The cut-off value in predicting death in patients with ischemic stroke and without diabetes was above 113.5 mg/dl, while in diabetics it was above 210.5 mg/dl.Hyperglycemia on admission is associated with worsened clinical outcome and increased risk of in-hospital death in ischemic and hemorrhagic stroke patients. Diabetes increased the risk of in-hospital death in hemorrhagic stroke patients, but not in ischemic ones.
| S-EPMC5206364 | biostudies-other