We research into the clinical, biochemical and neuroimaging factors associated with the outcome of stroke patients to generate a predictive model using machine learning techniques for prediction of ...mortality and morbidity 3-months after admission. The dataset consisted of patients with ischemic stroke (IS) and non-traumatic intracerebral hemorrhage (ICH) admitted to Stroke Unit of a European Tertiary Hospital prospectively registered. We identified the main variables for machine learning Random Forest (RF), generating a predictive model that can estimate patient mortality/morbidity according to the following groups: (1) IS + ICH, (2) IS, and (3) ICH. A total of 6022 patients were included: 4922 (mean age 71.9 ± 13.8 years) with IS and 1100 (mean age 73.3 ± 13.1 years) with ICH. NIHSS at 24, 48 h and axillary temperature at admission were the most important variables to consider for evolution of patients at 3-months. IS + ICH group was the most stable for mortality prediction 0.904 ± 0.025 of area under the receiver operating characteristics curve (AUC). IS group presented similar results, although variability between experiments was slightly higher (0.909 ± 0.032 of AUC). ICH group was the one in which RF had more problems to make adequate predictions (0.9837 vs. 0.7104 of AUC). There were no major differences between IS and IS + ICH groups according to morbidity prediction (0.738 and 0.755 of AUC) but, after checking normality with a Shapiro Wilk test with the null hypothesis that the data follow a normal distribution, it was rejected with W = 0.93546 (p-value < 2.2e-16). Conditions required for a parametric test do not hold, and we performed a paired Wilcoxon Test assuming the null hypothesis that all the groups have the same performance. The null hypothesis was rejected with a value < 2.2e-16, so there are statistical differences between IS and ICH groups. In conclusion, machine learning algorithms RF can be effectively used in stroke patients for long-term outcome prediction of mortality and morbidity.
Brain ischaemia (stroke) triggers an intense inflammatory response predominately mediated by the accumulation of inflammatory cells and mediators in the ischaemic brain. In this context, regulatory T ...(Treg) cells, a subpopulation of CD4+ T cells with immunosuppressive and anti‐inflammatory properties, are activated in the late stages of the disease. To date, the potential therapeutic usefulness of Treg cells has not been tested. In this study, we aimed to investigate whether Treg cells exert protection/repair following stroke. Both the adoptive transfer of Treg cells into ischaemic rats and the stimulation of endogenous T‐cell proliferation using a CD28 superagonist reduced the infarct size at 3–28 days following the ischaemic insult. Moreover, T cell‐treated animals had higher levels of FoxP3 and lower levels of IL‐1β, CD11b+ and CD68+ cells in the infarcted hemisphere when compared with control animals. However, T‐cell treatment did not alter the rate of proliferation of NeuN‐, NCAM‐ or CD31‐positive cells, thereby ruling out neurogenesis and angiogenesis in protection. These results suggest that adoptive transfer of T cells is a promising therapeutic strategy against the neurological consequences of stroke.
Abstract
Aim
To assess whether periodontitis is associated with cognitive decline and its progression as well as with certain blood‐based markers of Alzheimer's disease.
Materials and Methods
Data ...from a 2‐year follow‐up prospective cohort study (
n
= 101) was analysed. Participants with a previous history of hypertension and aged ≥60 years were included in the analysis. All of them received a full‐mouth periodontal examination and cognitive function assessments (Addenbrooke's Cognitive Examination (ACE) and Mini‐Mental State Examination MMSE). Plasma levels of amyloid beta (Aβ)
1‐40
, Aβ
1‐42
, phosphorylated and total Tau (p‐Tau and t‐Tau) were determined at baseline, 12 and 24 months.
Results
Periodontitis was associated with poor cognitive performance (MMSE:
β
= −1.5 0.6) and progression of cognitive impairment (hazard ratio HR = 1.8; 95% confidence interval: 1.0–3.1). Subjects with periodontitis showed greater baseline levels of p‐Tau (1.6 0.7 vs. 1.2 0.2 pg/mL,
p
< .001) and Aβ
1‐40
(242.1 77.3 vs. 208.2 73.8 pg/mL,
p
= .036) compared with those without periodontitis. Concentrations of the latter protein also increased over time only in the periodontitis group (
p
= .005).
Conclusions
Periodontitis is associated with cognitive decline and its progression in elderly patients with a previous history of hypertension. Overexpression of p‐Tau and Aβ
1‐40
may play a role in this association.
Several observational studies have suggested an association between periodontitis and cerebral ischemia. This meta-analysis aimed to investigate whether this link exists, and if so, the degree to ...which it is significant. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline for systematic review was used. The search strategy included using electronic databases and hand searching works published up to March 2015. MEDLINE via PubMed, EMBASE, Proceedings Web of Science and Current Contents Connect were searched by two independent reviewers. Case-control, crosssectional or cohort studies including patients with measures of periodontitis and ischémie stroke were eligible to be included in the analysis. Quality assessments of selected studies were performed. From a total of 414 titles and abstracts, 57 potentially relevant full text papers were identified. After inclusion criteria were applied, 8 studies were included in the present systematic review (5 case control and 3 cohort studies). Although it was not the intention, cross-sectional studies were excluded due to eligibility criteria were not accomplished. Therefore, meta-analyses were conducted with data retrieved from the 8 studies included. These meta-analyses showed statistically significant association between periodontitis and ischémie stroke in both cohort pooled relative risks at 2.52 (1.77-3.58), and case-control studies pooled relative risks at 3.04 (1.10-8.43). In conclusion, the present meta-analysis demonstrated an association between periodontitis and ischemic stroke. However, well-designed prospective studies should be carried out to provide robust evidence of the link between both diseases. In regards to ischemic stroke subtypes, further case-control studies should be carried out to investigate whether there is any association between the different subtypes of cerebral infarcts and periodontitis.
Background
Periodontitis has been associated with lacunar infarct (LI), a type of cerebral small vessel disease. The objective of this study was to ascertain whether periodontitis is associated with ...increased circulating levels of systemic inflammation and endothelial dysfunction biomarkers in patients with LI.
Methods
One hundred twenty patients with LI and 120 healthy controls underwent a full‐mouth periodontal examination. The periodontal inflamed surface area (PISA) was calculated for each participant. Demographic, medical, and neurological information were recorded from all of them. In addition, blood samples were collected in order to investigate differences in terms of interleukin (IL)‐6, IL‐10, pentraxin (PTX) 3, soluble fragment of tumor necrosis factor‐like weak inducer of apoptosis (sTWEAK) and amyloid‐beta (Aβ) peptides (i.e., Aβ1‐40, and Aβ1‐42) measured in serum.
Results
Periodontitis was independently associated with increased levels of IL‐6 (R2 = 0.656, P < 0.001), PTX3 (R2 = 0.115, P < 0.001), sTWEAK (R2 = 0.527, P < 0.001), and Aβ1‐40 (R2 = 0.467, P < 0.001) in patients with LI. Within patients with poor outcome, PISA positively correlated with IL‐6 (r = 0.738, P < 0.001), PTX3 (r = 0.468, P = 0.008), sTWEAK (r = 0.771, P < 0.001), and Aβ1‐40 (r = 0.745, P < 0.001).
Conclusions
Our data suggest a link between periodontitis, systemic inflammatory response, and disruption of the vascular endothelial function in patients with LI. Experimental studies are needed to elucidate possible pathways through which periodontitis could lead to this systemic inflammatory state with impairment of the endothelial function in LI. Further longitudinal studies with large samples are warranted to confirm our findings.
This study aimed to compare the effects of three resistance training (RT) programs differing in the magnitude of velocity loss (VL) allowed in each exercise set: 10%, 30%, or 45% on changes in ...strength, vertical jump, sprint performance, and EMG variables. Thirty‐three young men were randomly assigned into three experimental groups (VL10%, VL30%, and VL45%; n = 11 each) that performed a velocity‐based RT program for 8 weeks using only the full squat exercise (SQ). Training load (55–70% 1RM), frequency (2 sessions/week), number of sets (3), and inter‐set recovery (4 min) were identical for all groups. Running sprint (20 m), countermovement jump (CMJ), 1RM, muscle endurance, and EMG during SQ were assessed pre‐ and post‐training. All groups showed significant (VL10%: 6.4–58.6%; VL30%: 4.5–66.2%; VL45%: 1.8–52.1%; p < 0.05–0.001) improvements in muscle strength and muscle endurance. However, a significant group × time interaction (p < 0.05) was observed in CMJ, with VL10% showing greater increments (11.9%) than VL30% and VL45%. In addition, VL10% resulted in greater percent change in sprint performance than the other two groups (VL10%: −2.4%; VL30%: −1.8%; and VL45%: −0.5%). No significant changes in EMG variables were observed for any group. RT with loads of 55–70% 1RM characterized by a low‐velocity loss (VL10%) provides a very effective and efficient training stimulus since it yields similar strength gains and greater improvements in sports‐related neuromuscular performance (jump and sprint) compared to training with higher velocity losses (VL30%, VL45%). These findings indicate that the magnitude of VL reached in each exercise set considerably influences the observed training adaptations.
Objective
Blood/brain‐glutamate grabbing is an emerging concept in the treatment of acute ischemic stroke, where essentially the deleterious effects of glutamate after ischemia are ameliorated by ...coaxing glutamate to enter the bloodstream and thus reducing its concentration in the brain. Aiming to demonstrate the clinical efficacy of blood glutamate grabbers in patients with stroke, in this study, we resorted to a drug‐repositioning strategy for the discovery of new glutamate‐grabbing drugs.
Methods
The glutamate‐grabbing ability of 1,120 compounds (90% of which were drugs approved by the US Food and Drug Administration) was evaluated during an in vitro high‐throughput screening campaign. Subsequently, the protective efficacy of the selected drugs was probed in an ischemic animal model and finally tested in stroke patients.
Results
Riboflavin (vitamin B2) was identified as the main hit compound. In ischemic animal models treated with riboflavin (1mg/kg), it was confirmed that blood glutamate reduction was associated with a significant reduction of infarct size. These results led to a randomized, double‐blind, phase IIb clinical trial with patients with stroke. Fifty patients were randomized to 1 of the 2 study arms: the control group (placebo) and the experimental group (20mg of riboflavin vitamin B2 Streuli@). Decrease in glutamate concentration was significantly greater (p < 0.029) in the treated group. Comparative analysis of the percentage improvement on the National Institutes of Health Stroke Scale score at discharge was slightly higher in the riboflavin‐treated group than in the placebo group (33.7 ± 43.7 vs 48.9 ± 42.4%, p = 0.050).
Interpretation
This translational study represents the first human demonstration of the efficacy of blood glutamate grabbers in the treatment of patients with stroke, paving the way for the development of a promising novel protective therapy. Ann Neurol 2018;84:260–273
Aim
To investigate the association between periodontitis (PD) and lacunar infarct (LI) as well as to analyse whether PD could be a predictor of poor functional prognosis in patients with LI.
Material ...and Methods
Full‐mouth periodontal examination was done in 120 cases (patients with LI) and 157 healthy controls. Demographic, clinical, medical and neurological information were collected from all of them. In addition, a measure of periodontal inflammation and disease activity, namely the periodontal inflamed surface area (PISA), was also calculated for each patient. Poor functional outcome was considered as a modified Rankin Scale >2 at 3 months.
Results
PD was independently associated with the presence of LI (OR = 3.3, p < 0.001). Poor outcome was observed in 31 patients with LI (25.8%), of which 90.3% had PD. A PISA value ≥727 mm2 was an independent predictor of poor prognosis, after adjusting for clinical confounders (OR = 6.5, p = 0.001).
Conclusions
PD and LI were associated. Active moderate to severe PD predicted poor prognosis in patients with LI. Further evidence is warranted to confirm our results and investigate potential mechanisms behind this association.
Background
Successful recanalization does not lead to complete tissue reperfusion in a considerable percentage of ischemic stroke patients. This study aimed to identify biomarkers associated with ...futile recanalization. Leukoaraiosis predicts poor outcomes of this phenomenon. Soluble tumour necrosis factor‐like weak inducer of apoptosis (sTWEAK), which is associated with leukoaraiosis degrees, could be a potential biomarker.
Methods
This study includes two cohorts of ischemic stroke patients in a multicentre retrospective observational study. Effective reperfusion, defined as a reduction of ≥8 points in the National Institutes of Health Stroke Scale (NIHSS) within the first 24 h, was used as a clinical marker of effective reperfusion.
Results
In the first cohort study, female sex, age, and high NIHSS at admission (44.7% vs. 81.1%, 71.3 ± 13.7 vs. 81.1 ± 6.7; 16 13, 21 vs. 23 17, 28 respectively; p < .0001) were confirmed as predictors of futile recanalization. ROC curve analysis showed that leukocyte levels (sensitivity of 99%, specificity of 55%) and sTWEAK level (sensitivity of 92%, specificity of 88%) can discriminate between poor and good outcomes. Both biomarkers simultaneously are higher associated with outcome after effective reperfusion (OR: 2.17; CI 95% 1.63–4.19; p < .0001) than individually (leukocytes OR: 1.38; CI 95% 1.00–1.64, p = .042; sTWEAK OR: 1.00; C I95% 1.00–1.01, p = .019). These results were validated using a second cohort, where leukocytes and sTWEAK showed a sensitivity of 100% and specificity of 66.7% and 75% respectively.
Conclusions
Leukocyte and sTWEAK could be biomarkers of reperfusion failure and subsequent poor outcomes. Further studies will be necessary to explore its role in reperfusion processes.
Successfully recanalization does not always lead to complete tissue reperfusion in ischemic stroke patients. This multicentre retrospective observational study included two cohorts. ROC curve analysis in both cohorts showed that leukocytes and sTWEAK can discriminate between poor and good outcomes. Both biomarkers simultaneously are higher associated with outcome after effective reperfusion than individually. Therefore, both could be biomarkers of reperfusion failure and subsequent poor outcomes.
Recent preclinical studies have shown that regulatory T cells (Treg) play a key role in the immune response after ischemic stroke (IS). However, the role of Treg in human acute IS has been poorly ...investigated. Our aim was to study the relationship between circulating Treg and outcome in human IS patients.
A total of 204 IS patients and 22 control subjects were recruited. The main study variable was good functional outcome at 3 months (modified Rankin scale ≤2) considering infarct volume, Early Neurological Deterioration (END) and risk of infections as secondary variables. The percentage of circulating Treg was measured at admission, 48, 72 h and at day 7 after stroke onset.
Circulating Treg levels were higher in IS patients compared to control subjects. Treg at 48 h were independently associated with good functional outcome (OR, 3.5; CI: 1.9-7.8) after adjusting by confounding factors. Patients with lower Treg at 48 h showed higher frequency of END and risk of infections. In addition, a negative correlation was found between circulating Treg at 48 h (r = - 0.414) and 72 h (r = - 0.418) and infarct volume.
These findings suggest that Treg may participate in the recovery of IS patients. Therefore, Treg may be considered a potential therapeutic target in acute ischemic stroke.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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