Remote ischemic conditioning (RIC) is a promising therapeutic approach for ischemic stroke patients. It has been proven that RIC reduces infarct size and improves functional outcomes. RIC can be ...applied either before ischemia (pre-conditioning; RIPreC), during ischemia (per-conditioning; RIPerC) or after ischemia (post-conditioning; RIPostC). Our aim was to systematically determine the efficacy of RIC in reducing infarct volumes and define the cellular pathways involved in preclinical animal models of ischemic stroke. A systematic search in three databases yielded 50 peer-review articles. Data were analyzed using random effects models and results expressed as percentage of reduction in infarct size (95% CI). A meta-regression was also performed to evaluate the effects of covariates on the pooled effect-size. 95.3% of analyzed experiments were carried out in rodents. Thirty-nine out of the 64 experiments studied RIPostC (61%), sixteen examined RIPreC (25%) and nine tested RIPerC (14%). In all studies, RIC was shown to reduce infarct volume (- 38.36%; CI - 42.09 to - 34.62%) when compared to controls. There was a significant interaction caused by species. Short cycles in mice significantly reduces infarct volume while in rats the opposite occurs. RIPreC was shown to be the most effective strategy in mice. The present meta-analysis suggests that RIC is more efficient in transient ischemia, using a smaller number of RIC cycles, applying larger length of limb occlusion, and employing barbiturates anesthetics. There is a preclinical evidence for RIC, it is safe and effective. However, the exact cellular pathways and underlying mechanisms are still not fully determined, and its definition will be crucial for the understanding of RIC mechanism of action.
COVID-19 may predispose to both venous and arterial thromboembolism event (TEE). Reports on the prevalence and prognosis of thrombotic complications are still emerging. To describe the rate of TEE ...complications and its influence in the prognosis of hospitalized patients with COVID-19 after a cross-sectional study. We evaluated the prevalence of TEE and its relationship with in-hospital death among hospitalized patients with COVID-19 who were admitted between 1st March to 20th April 2020 in a multicentric network of sixteen Hospitals in Spain. TEE was defined by the occurrence of venous thromboembolism (VTE), acute ischemic stroke (AIS), systemic arterial embolism or myocardial infarction (MI). We studied 1737 patients with proven COVID-19 infection of whom 276 died (15.9%). TEE were presented in 64 (3.7%) patients: 49 (76.6%) patients had a VTE, 8 (12.5%) patients had MI, 6 (9.4%%) patients had AIS, and one (1.5%) patient a thrombosis of portal vein. TEE patients exhibited a diffuse profile: older, high levels of D-dimer protein and a tendency of lower levels of prothrombin. The multivariate regression models, confirmed the association between in-hospital death and age (odds ratio OR 1.12 95% CI 1.10-1.14, p<0.001), diabetes (OR 1.49 95% CI 1.04-2.13, p = 0.029), chronic obstructive pulmonary disease (OR 1.61 95% CI 1.03-2.53, p = 0.039), ICU care (OR 9.39 95% CI 5.69-15.51, p<0.001), and TTE (OR 2.24 95% CI 1.17-4.29, p = 0.015). Special attention is needed among hospitalized COVID-19 patients with TTE and other comorbidities as they have an increased risk of in-hospital death.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Senescent cells are capable of expressing a myriad of inflammatory cytokines and this pro-inflammatory phenomenon is known as senescence-associated secretory phenotype (SASP). The ...contribution of this phenomenon in brain ischemia was scarce. A mouse model of transient focal cerebral ischemia by compressing the distal middle cerebral artery (tMCAo) for 60 min was used. SASP, pro-inflammatory cytokines and cell cycle mRNAs levels were quantified at 30-min and 72 h post-surgery. Immunohistochemistry in paraffin embedded human brain slides and mouse brain tissue was performed. Our results showed an increase of both
p16
and
p21
mRNA restricted to the infarct area in the tMCAo brain. Moreover, there was an induction of
Il6
,
Tnfa
,
Cxc11,
and its receptor
Cxcr2
mRNA pro-inflammatory cytokines with a high positive correlation with
p16
/
p21
mRNA levels. The p16 was mainly shown in cytoplasm of neurons and cytoplasm/membrane of microglial cells. The p21 was observed in membrane of neurons and also it showed a mixed cytoplasmic and membranous pattern in the microglial cells. In a human stroke patient, an increase of P16 in the perimeter of the MCA infarct area was observed. These suggest a role of SASP in tMCAo mouse model and in human brain tissue. SASP potentially has a physiological role in acute ischemic stroke and neurological function loss.
Stroke is a major cause of neurological morbidity and mortality. Atherosclerosis is a major contributor to first and recurrent stroke. A growing evidence base indicates that inflammation is a key ...process in the pathogenesis of atherosclerosis, leading to thromboembolic events. In this review, we summarise the evidence linking inflammation to stroke risk and discuss clinical trials addressing the 'inflammation hypothesis' in coronary disease and stroke.
CONVINCE trial ClinicalTrials.gov number; NCT 02898610; Pre-results.
Abstract
We aimed to find out which are the most frequent complications for patients who suffer a traumatic brain injury (TBI) and its relation with brain biomarker levels. We conducted a hospital ...cohort study with patients who attended the Hospital Emergency Department between 1 June 2018 and 31 December 2020. Different variables were collected such as biomarkers levels after 6 h and 12 h of TBI (S100, NSE, UCHL1 and GFAP), clinical and sociodemographic variables, complementary tests, and complications 48 h and 7 days after TBI. Qualitative variables were analysed with Pearson’s chi-square test, and quantitative variables with the Mann–Whitney
U
test. A multivariate logistic regression model for the existence of complications one week after discharge was performed to assess the discriminatory capacity of the clinical variables. A total of 51 controls and 540 patients were included in this study. In the TBI group, the mean age was 83 years, and 53.9% of the patients were male. Complications at seven days were associated with the severity of TBI (p < 0.05) and the number of platelets (p = 0.016). All biomarkers except GFAP showed significant differences in their distribution of values according to gender, with significantly higher values of the three biomarkers for women with respect to men. Patients with complications presented significantly higher S100 values (p < 0.05). The patient’s baseline status, the severity of the TBI and the S100 levels can be very important elements in determining whether a patient may develop complications in the few hours after TBI.
Summary Background Identification of patients at highest risk of early stroke after transient ischaemic attack has been improved with imaging based scores. We aimed to compare the validity and ...prognostic utility of imaging-based stroke risk scores in patients after transient ischaemic attack. Methods We did a pooled analysis of published and unpublished individual-patient data from 16 cohort studies of transient ischaemic attack done in Asia, Europe, and the USA, with early brain and vascular imaging and follow up. All patients were assessed by stroke specialists in hospital settings as inpatients, in emergency departments, or in transient ischaemic attack clinics. Inclusion criteria were stroke-specialist confirmed transient ischaemic attack, age of 18 years or older, and MRI done within 7 days of index transient ischaemic attack and before stroke recurrence. Multivariable logistic regression was done to analyse the predictive utility of abnormal diffusion-weighted MRI, carotid stenosis, and transient ischaemic attack within 1 week of index transient ischaemic attack (dual transient ischaemic attack) after adjusting for ABCD2 score. We compared the prognostic utility of the ABCD2, ABCD2-I, and ABCD3-I scores using discrimination, calibration, and risk reclassification. Findings In 2176 patients from 16 cohort studies done between 2005 and 2015, after adjusting for ABCD2 score, positive diffusion-weighted imaging (odds ratio OR 3·8, 95% CI 2·1–7·0), dual transient ischaemic attack (OR 3·3, 95% CI 1·8–5·8), and ipsilateral carotid stenosis (OR 4·7, 95% CI 2·6–8·6) were associated with 7 day stroke after index transient ischaemic attack (p<0·001 for all). 7 day stroke risk increased with increasing ABCD2-I and ABCD3-I scores (both p<0·001). Discrimination to identify early stroke risk was improved for ABCD2-I versus ABCD2 (2 day c statistic 0·74 vs 0·64; p=0·006). However, discrimination was further improved by ABCD3-I compared with ABCD2 (2 day c statistic 0·84 vs 0·64; p<0·001) and ABCD2-I ( c statistic 0·84 vs 0·74; p<0·001). Early stroke risk reclassification was improved by ABCD3-I compared with ABCD2-I score (clinical net reclassification improvement 33% at 2 days). Interpretation Although ABCD2-I and ABCD3-I showed validity, the ABCD3-I score reliably identified highest-risk patients at highest risk of a stroke after transient ischaemic attack with improved risk prediction compared with ABCD2-I. Transient ischaemic attack management guided by ABCD3-I with immediate stroke-specialist assessment, urgent MRI, and vascular imaging should now be considered, with monitoring of safety and cost-effectiveness. Funding Health Research Board of Ireland, Irish Heart Foundation, Irish Health Service Executive, Irish National Lottery, National Medical Research Council of Singapore, Swiss National Science Foundation, Bangerter-Rhyner Foundation, Swiss National Science Foundation, Swisslife Jubiläumsstiftung for Medical Research, Swiss Neurological Society, Fondazione Dr Ettore Balli (Switzerland), Clinical Trial Unit of University of Bern, South Korea's Ministry for Health, Welfare, and Family Affairs, UK Wellcome Trust, Wolfson Foundation, UK Stroke Association, British Heart Foundation, Dunhill Medical Trust, National Institute of Health Research (NIHR), Medical Research Council, and the NIHR Oxford Biomedical Research Centre.
Anti-inflammatory therapies reduce major adverse cardiovascular events (MACE) in coronary artery disease but remain unproven after stroke. Establishing the subtype-specific association between ...inflammatory markers and recurrence risk is essential for optimal selection of patients in randomized trials (RCTs) of anti-inflammatory therapies for secondary stroke prevention.
Using individual participant data (IPD) identified from a systematic review, we analyzed the association between high-sensitivity C-reactive protein, interleukin-6 (IL-6), and vascular recurrence after ischemic stroke or transient ischemic attack. The prespecified coprimary end points were (1) any recurrent MACE (first major coronary event, recurrent stroke, or vascular death) and (2) any recurrent stroke (ischemic, hemorrhagic, or unspecified) after sample measurement. Analyses were performed stratified by stroke mechanism, per quarter and per biomarker unit increase after log
transformation. We then did study-level meta-analysis with comparable published studies not providing IPD. Preferred Reporting Items for Systematic Review and Meta-Analyses IPD guidelines were followed.
IPD was obtained from 10 studies (8,420 patients). After adjustment for vascular risk factors and statins/antithrombotic therapy, IL-6 was associated with recurrent MACE in stroke caused by large artery atherosclerosis (LAA) (risk ratio RR 2.30, 95% CI 1.21-4.36,
= 0.01), stroke of undetermined cause (UND) (RR 1.78, 1.19-2.66,
= 0.005), and small vessel occlusion (SVO) (RR 1.71, 0.99-2.96,
= 0.053) (quarter 4 Q4 vs quarter 1 Q1). No association was observed for stroke due to cardioembolism or other determined cause. Similar results were seen for recurrent stroke and when analyzed per log
unit increase for MACE (LAA, RR 1.26 1.06-1.50,
= 0.009; SVO, RR 1.22 1.01-1.47,
= 0.04; UND, RR 1.18 1.04-1.34,
= 0.01). High-sensitivity CRP was associated with recurrent MACE in UND stroke only (Q4 vs Q1 RR 1.45 1.04-2.03,
= 0.03). Findings were consistent on study-level meta-analysis of the IPD results with 2 other comparable studies (20,136 patients).
Our data provide new evidence for the selection of patients in future RCTs of anti-inflammatory therapy in stroke due to large artery atherosclerosis, small vessel occlusion, and undetermined etiology according to inflammatory marker profile.
Abstract
To evaluate whether preventive treatment can modify endothelial and oxidative biomarkers of vascular disease risk in patients with high-frequency episodic and chronic migraine. In this ...observational, prospective pilot study, 88 prophylactic treatment-naïve patients with episodic and chronic migraine and 56 healthy sex/age matched controls underwent ultrasonography exams and blood tests at baseline, and again in the migraine patients after 3 months’ treatment with metoprolol or topiramate. Biomarkers for endothelial function and oxidative stress were analyzed. At baseline, patients with migraine in the low-frequency episodic group had differences exclusively in nitrates 17.6 versus 27.33 µM;
p
= 0.046 compared to the controls. However, when comparing the group comprised of patients with high-frequency episodic migraine and chronic migraine versus controls, statistically significant differences appeared in hsCRP 2.68 versus 1.64 mg/dL;
p
= 0.049, vWF antigen (133% vs. 110%;
p
= 0.020, vWF activity (111% vs. 90%;
p
= 0.010) and isoprostane levels (181 vs. 238 µM;
p
= 0.05). Only in the chronic migraine subgroup did we found statistically significant differences in CIMT (0.60 vs. 0.54 mm;
p
= 0.042) which were significantly greater than in the controls. After treatment, patients who respond to preventive treatment exhibited significantly higher levels of nitrates (24.2–13.8 µM;
p
= 0.022) and nitrites (10.4–3.43 µM;
p
= 0.002) compared than non-responders. Moreover, biomarker levels improved in treatment-responsive patients with migraine; hsCRP levels decreased from 2.54 to 1.69 mg/dL (
p
< 0.05), vWF activity levels decreased from 124 to 103 IU/dL (
p
= 0.003) and prothrombin activity decreased from 1.01 to 0.93 (
p
= 0.01). These differences were also observed in the high-frequency and chronic migraine subgroup and reach statistical significance in the case of hsCRP, which decreased from 2.12 to 0.83 mg/dL (
p
= 0.048). Patients with migraines have differences in biomarker levels compared to controls, suggesting endothelial and oxidative dysfunction. The greatest differences in biomarker levels compared to controls are observed in migraine patients in the high-frequency and chronic migraine subgroups. Based on our results, preventive treatment is capable of modifying markers of endothelial dysfunction and oxidative stress in migraine patients, even in cases of chronic and high-frequency migraine.
OBJECTIVE:To discover, by using metabolomics, novel candidate biomarkers for stroke recurrence (SR) with a higher prediction power than present ones.
METHODS:Metabolomic analysis was performed by ...liquid chromatography coupled to mass spectrometry in plasma samples from an initial cohort of 131 TIA patients recruited <24 hours after the onset of symptoms. Pattern analysis and metabolomic profiling, performed by multivariate statistics, disclosed specific SR and large-artery atherosclerosis (LAA) biomarkers. The use of these methods in an independent cohort (162 subjects) confirmed the results obtained in the first cohort.
RESULTS:Metabolomics analyses could predict SR using pattern recognition methods. Low concentrations of a specific lysophosphatidylcholine (LysoPC16:0) were significantly associated with SR. Moreover, LysoPC(20:4) also arose as a potential SR biomarker, increasing the prediction power of age, blood pressure, clinical features, duration of symptoms, and diabetes scale (ABCD2) and LAA. Individuals who present early (<3 months) recurrence have a specific metabolomic pattern, differing from non-SR and late SR subjects. Finally, a potential LAA biomarker, LysoPC(22:6), was also described.
CONCLUSIONS:The use of metabolomics in SR biomarker research improves the predictive power of conventional predictors such as ABCD2 and LAA. Moreover, pattern recognition methods allow us to discriminate not only SR patients but also early and late SR cases.
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