Safety of intravenous thrombolysis for acute ischemic stroke in patients receiving antiplatelet therapy at stroke onset

<p><b>Background and Purpose:</b> Antiplatelets (APs) may increase the risk of symptomatic intracerebral hemorrhage (ICH) following intravenous thrombolysis after ischemic stroke.</p> <p><b>Methods:</b> We assessed the safety of thrombolysis under APs in 11 865 patients compliant with the European license criteria and recorded between 2002 and 2007 in the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register (SITS-ISTR). Outcome measures of univariable and multivariable analyses included symptomatic ICH (SICH) per SITS Monitoring Study (SITS-MOST [deterioration in National Institutes of Health Stroke Scale >= 4 plus ICH type 2 within 24 hours]), per European Cooperative Acute Stroke Study II (ECASS II [deterioration in National Institutes of Health Stroke Scale >= 4 plus any ICH]), functional outcome at 3 months and mortality.</p> <p><b>Results:</b> A total of 3782 (31.9%) patients had received 1 or 2 AP drugs at baseline: 3016 (25.4%) acetylsalicylic acid (ASA), 243 (2.0%) clopidogrel, 175 (1.5%) ASA and dipyridamole, 151 (1.3%) ASA and clopidogrel, and 197 (1.7%) others. Patients receiving APs were 5 years older and had more risk factors than AP nave patients. Incidences of SICH per SITS-MOST (ECASS II respectively) were as follows: 1.1% (4.1%) AP naive, 2.5% (6.2%) any AP, 2.5% (5.9%) ASA, 1.7% (4.2%) clopidogrel, 2.3% (5.9%) ASA and dipyridamole, and 4.1% (13.4%) ASA and clopidogrel. In multivariable analyses, the combination of ASA and clopidogrel was associated with increased risk for SICH per ECASS II (odds ratio, 2.11; 95% CI, 1.29 to 3.45; P = 0.003). However, we found no significant increase in the risk for mortality or poor functional outcome, irrespective of the AP subgroup or SICH definition.</p> <p><b>Conclusion:</b> The absolute excess of SICH of 1.4% (2.1%) in the pooled AP group is small compared with the benefit of thrombolysis seen in randomized trials. Although caution is warranted in patients receiving the combination of ASA and clopidogrel, AP treatment should not be considered a contraindication to thrombolysis.</p&gt

Oral Levosimendan Increases Cerebral Blood Flow Velocities in Patients with a History of Stroke or Transient Ischemic Attack : A Pilot Safety Study

Peer reviewe

Gene expression differences between stroke-associated and asymptomatic carotid plaques

Atherosclerotic carotid stenosis is an important risk factor for stroke. Carotid plaques (CPs) causing stroke may present a distinct type of molecular pathology compared with transient ischemic attack (TIA)-associated or asymptomatic plaques. We compared the gene expression profiles of CPs from stroke patients (n = 12) and asymptomatic patients (n = 9), both with similar risk factors and severity of carotid stenosis (>70%). Sixty probes showed over 1.5-fold expression difference at 5% false discovery rate. Functional clustering showed enrichment of genes in 51 GO categories and seven pathways, the most significant of which relate to extracellular-matrix interaction, PPAR gamma signaling, scavanger receptor activity, and lysosomal activity. Differential expression of ten genes was confirmed in an extended replication group (n = 43), where the most significant expression differences were found in CD36 (2.1-fold change, p = 0.005), CD163 (1.7-fold change, p = 0.007) and FABP4 (2.2-fold change, p = 0.015). These include four genes not previously linked to plaque destabilization: GLUL (2.2-fold change, p = 0.016), FUCA1 (2.2-fold change, p = 0.025), IL1RN (1.6-fold change, p = 0.034), and S100A8 (2.5-fold change, p = 0.047). Strong correlations were found to plaque ulceration, plaque hemorrhage, and markers of apoptosis and proliferation (activated caspase 3, TUNEL, and Ki67). Protein expression of these genes was confirmed by immunohistochemistry and was found in the atheromatous areas of CPs critical for plaque destabilization. This study presents a comprehensive transcriptional analysis of stroke-associated CPs and demonstrates a significant transcriptome difference between stroke-associated and asymptomatic CPs. Follow-up studies on the identified genes are needed to define whether they could be used as biomarkers of symptomatic CPs or have a role in plaque destabilization

Determining the effect of drying time on phosphorus solubilization from three agricultural soils under climate change scenarios

Climate projections for the future indicate that the United Kingdom will experience hotter, drier summers and warmer, wetter winters, bringing longer dry periods followed by rewetting. This will result in changes in phosphorus (P) mobilization patterns that will influence the transfer of P from land to water. We tested the hypothesis that changes in the future patterns of drying–rewetting will affect the amount of soluble reactive phosphorus (SRP) solubilized from soil. Estimations of dry period characteristics (duration and temperature) under current and predicted climate were determined using data from the UK Climate Projections (UKCP09) Weather Generator tool. Three soils (sieved 25°C are predicted in some places and dry periods of 30 to 90 d extremes are predicted. Combining the frequency of projected dry periods with the SRP concentration in leachate suggests that this may result overall in increased mobilization of P; however, critical breakpoints of 6.9 to 14.5 d dry occur wherein up to 28% more SRP can be solubilized following a rapid rewetting event. The precise cause of this increase could not be identified and warrants further investigation as the process is not currently included in P transfer models

Estimated GFR and the Effect of Intensive Blood Pressure Lowering after Acute Intracerebral Hemorrhage

Background: The kidney-brain interaction has been a topic of growing interest. Past studies of the effect of kidney function on intracerebral hemorrhage (ICH) outcomes have yielded inconsistent findings. Although the second, main phase of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) suggests the effectiveness of early intensive blood pressure (BP) lowering in improving functional recovery after ICH, the balance of potential benefits and harms of this treatment in those with decreased kidney function remains uncertain. Study Design: Secondary analysis of INTERACT2, which randomly assigned patients with ICH with elevated systolic BP (SBP) to intensive (target SBP 90, 60-90, and <60 mL/min/1.73 m2, respectively). Outcomes: The effect of admission eGFR on the primary outcome of death or major disability at 90 days (defined as modified Rankin Scale scores of 3-6) was analyzed using a multivariable logistic regression model. Potential effect modification of intensive BP lowering treatment by admission eGFR was assessed by interaction terms. Results: Of 2,623 included participants, 912 (35%) and 280 (11%) had mildly and moderately/severely decreased eGFRs, respectively. Patients with moderately/severely decreased eGFRs had the greatest risk for death or major disability at 90 days (adjusted OR, 1.82; 95% CI, 1.28-2.61). Effects of early intensive BP lowering were consistent across different eGFRs (P = 0.5 for homogeneity). Limitations: Generalizability issues arising from a clinical trial population. Conclusions: Decreased eGFR predicts poor outcome in acute ICH. Early intensive BP lowering provides similar treatment effects in patients with ICH with decreased eGFRs

The Role of Perfusion Computed Tomography in the Prediction of Cerebral Hyperperfusion Syndrome

Hyperperfusion syndrome (HPS) following carotid angioplasty with stenting (CAS) is associated with significant morbidity and mortality. At present, there are no reliable parameters to predict HPS. The aim of this study was to clarify whether perfusion computed tomography (CT) is a feasible and reliable tool in predicting HPS after CAS.We performed a retrospective case-control study of 54 patients (11 HPS patients and 43 non-HPS) with unilateral severe stenosis of the carotid artery who underwent CAS. We compared the prevalence of vascular risk factors and perfusion CT parameters including regional cerebral blood volume (rCBV), regional cerebral blood flow (rCBF), and time to peak (TTP) within seven days prior to CAS. Demographic information, risk factors for atherosclerosis, and perfusion CT parameters were evaluated by multivariable logistic regression analysis. The rCBV index was calculated as [(ipsilateral rCBV - contralateral rCBV)/contralateral rCBV], and indices of rCBF and TTP were similarly calculated. We found that eleven patients had HPS, including five with intracranial hemorrhages (ICHs) of whom three died. After a comparison with non-HPS control subjects, independent predictors of HPS included the severity of ipsilateral carotid artery stenosis, 3-hour mean systolic blood pressure (3 h SBP) after CAS, pre-stenting rCBV index >0.15 and TTP index >0.22.The combination of severe ipsilateral carotid stenosis, 3 h SBP after CAS, rCBV index and TTP index provides a potential screening tool for predicting HPS in patients with unilateral carotid stenosis receiving CAS. In addition, adequate management of post-stenting blood pressure is the most important treatable factor in preventing HPS in these high risk patients

Food webs under changing biodiversity - Top-down control

Report on effects of changing predation pressure on benthic and pelagic specie

Dissolved organic matter in the Baltic Sea

Several factors highlight the importance of dissolved organic matter (DOM) in coastal ecosystems such as the Baltic Sea: 1) DOM is the main energy source for heterotrophic bacteria in surface waters, thus contributing to the productivity and trophic state of bodies of water. 2) DOM functions as a nutrient source: in the Baltic Sea, more than one-fourth of the bioavailable nutrients can occur in the dissolved organic form in riverine inputs and in surface water during summer. Thus, DOM also supports primary production, both directly (osmotrophy) and indirectly (via remineralization). 3) Flocculation and subsequent deposition of terrestrial DOM within river estuaries may contribute to production and oxygen consumption in coastal sediments. 4) Chromophoric DOM, which is one of the major absorbers of light entering the Baltic Sea, contributes highly to water color, thus affecting the photosynthetic depth as well as recreational value of the Baltic Sea. Despite its large-scale importance to the Baltic Sea ecosystem, DOM has been of minor interest compared with inorganic nutrient loadings. Information on the concentrations and dynamics of DOM in the Baltic Sea has accumulated since the late 1990s, but it is still sporadic. This review provides a coherent view of the current understanding of DOM dynamics in the Baltic Sea.201

Thrombolysis outcomes in acute ischemic stroke patients with prior stroke and diabetes mellitus

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Patients with concomitant diabetes mellitus (DM) and prior stroke (PS) were excluded from European approval of alteplase in stroke. We examined the influence of DM and PS on the outcomes of patients who received thrombolytic therapy (T; data from Safe Implementation of Thrombolysis in Stroke–International Stroke Thrombolysis Register) compared to nonthrombolyzed controls (C; data from Virtual International Stroke Trials Archive).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; We selected ischemic stroke patients on whom we held data on age, baseline NIH Stroke Scale score (NIHSS), and 90-day modified Rankin Scale score (mRS). We compared the distribution of mRS between T and C by Cochran-Mantel-Haenszel (CMH) test and proportional odds logistic regression, after adjustment for age and baseline NIHSS, in patients with and without DM, PS, or the combination. We report odds ratios (OR) for improved distribution of mRS with 95% confidence interval (CI) and CMH p value.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Data were available for 29,500 patients: 5,411 (18.5%) had DM, 5,019 had PS (17.1%), and 1,141 (5.5%) had both. Adjusted mRS outcomes were better for T vs C among patients with DM (OR 1.45 [1.30–1.62], n = 5,354), PS (OR 1.55 [1.40–1.72], n = 4,986), or concomitant DM and PS (OR 1.23 [0.996–1.52], p = 0.05, n = 1,136), all CMH p &#60; 0.0001. These are comparable to outcomes between T and C among patients with neither DM nor PS: OR = 1.53 (1.42–1.63), p &#60; 0.0001, n = 19,339. There was no interaction on outcome between DM and PS with alteplase treatment (tissue plasminogen activator × DM × PS, p = 0.5). Age &#8804;80 years or &#62;80 years did not influence our findings.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Outcomes from thrombolysis are better than the controls among patients with DM, PS, or both. We find no statistical justification for the exclusion of these patients from receiving thrombolytic therapy.&lt;/p&gt