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

Effects of Training on Physical Performance Wearing Personal Protective Equipment

We evaluated the effects of wearing a weighted vest during 6 weeks of military-style training. Forty-three subjects were randomly assigned to a control group or a vest group (carrying 4-5 kg for 2 weeks, and 8-10 kg for 4 weeks), with 37 completing the study (17 vest, 20 control). Both groups performed stair climbing in addition to standard Marine Corps training for 1 hour, four times per week. Pre- and post-tests were performed while wearing military personal protective equipment, with the exception of the Marine Physical Readiness Test (PRT). Both groups significantly improved PRT scores (8.4% 3-mile run, 28-38% calisthenics) and an agility drill (4.4%). Significant improvements in uphill treadmill performance (6.8% vest, 3.0% control) and maximal oxygen consumption (10.7% vest, 6.8% control) were approximately twice as much in the vest versus control group, although these differences did not reach significance (p = 0.16 and 0.13, respectively)

Growth and shape of indium islands on molybdenum at micro-roughened spots created by femtosecond laser pulses

Indium islands on molybdenum coated glass can be grown in ordered arrays by surface structuring using a femtosecond laser. The effect of varying the molybdenum coated glass substrate temperature and the indium deposition rate on island areal density, volume and geometry is investigated and evaluated in a physical vapor deposition (PVD) process. The joined impact of growth conditions and spacing of the femtosecond laser structured spots on the arrangement and morphology of indium islands is demonstrated. The results yield a deeper understanding of the island growth and its precise adjustment to industrial requirements, which is indispensable for a technological application of such structures at a high throughput, for instance as precursors for the preparation of Cu(In,Ga)Se2 micro concentrator solar cells

Carotid stenting: is there an operator effect? A pooled analysis from the carotid stenting trialists' collaboration.

BACKGROUND AND PURPOSE: Randomized clinical trials show higher 30-day risk of stroke or death after carotid artery stenting compared with surgery. We examined whether operator experience is associated with 30-day risk of stroke or death in the Carotid Stenting Trialists' Collaboration database. METHODS: The Carotid Stenting Trialists' Collaboration is a pooled individual patient database including all patients recruited in 3 randomized trials of stenting versus endarterectomy for symptomatic carotid stenosis (Endarterectomy Versus Angioplasty in patients with Symptomatic Severe Carotid Stenosis trial, Stent-Protected Angioplasty versus Carotid Endarterectomy trial, and International Carotid Stenting Study). Lifetime carotid artery stenting experience, lifetime experience in stenting procedures excluding the carotid, and annual number of procedures performed within the trial (in-trial volume), divided into tertiles, were used to measure operator experience. The outcome event was the occurrence of any stroke or death within 30 days of the procedure. The analysis was done per protocol. RESULTS: Among 1546 patients who underwent carotid artery stenting, 120 (7.8%) had a stroke or death within 30 days of the procedure. The 30-day risk of stroke or death did not differ according to operator lifetime carotid artery stenting experience (P=0.8) or operator lifetime stenting experience excluding the carotid (P=0.7). In contrast, the 30-day risk of stroke or death was significantly higher in patients treated by operators with low (mean ≤3.2 procedures/y; risk 10.1%; adjusted risk ratio=2.30 [1.36-3.87]) and intermediate annual in-trial volumes (3.2-5.6 procedures/y; 8.4%; adjusted risk ratio=1.93 [1.14-3.27]) compared with patients treated by high annual in-trial volume operators (>5.6 procedures/y; 5.1%). CONCLUSIONS: Carotid stenting should only be performed by operators with annual procedure volume ≥6 cases per year

Modulation of Liver Inflammation and Fibrosis by Interleukin-37

Background and Aims: Chronic inflammation induces liver fibrosis, cirrhosis and potentially liver cancer. Kupffer cells modulate hepatic stellate cells by secreting immunologically active proteins as TGF-beta. TGF-beta promotes liver fibrosis via the activation of Sma- and Mad-related protein 3. IL-37 broadly suppresses innate and adaptive immune responses. Intracellular IL-37 interacts with Smad3. We hypothesize that IL-37 downregulates the activation of hepatic Kupffer and stellate cells and interferes with the TGF-beta signaling cascade to modulate liver fibrogenesis. Methods: The role of IL-37 on liver inflammation and fibrogenesis was assessed in three mouse models as well as isolated Kupffer- and stellate cells. Serum IL-37 was tested by ELISA in a clinical cohort and correlated with liver disease severity. Results: Transgene expression of IL-37 in mice extends survival, reduces hepatic damage, expression of early markers of fibrosis and histologically assessed liver fibrosis after bile duct ligation. IL-37tg mice were protected against CCl4-induced liver inflammation. Colitis-associated liver inflammation and fibrosis was less severe in IL-10 knockout IL-37tg mice. Spontaneous and LPS/TGF-beta-induced cytokine release and profibrogenic gene expression was lower in HSC and KC isolated from IL-37tg mice and IL-37 overexpressing, IL-1 beta stimulated human LX-2 stellate cells. However, administration of recombinant human IL-37 did not modulate fibrosis pathways after BDL in mice, LX2 cells or murine HSCs. In a large clinical cohort, we observed a positive correlation of serum IL-37 levels with disease severity in liver cirrhosis. Conclusions: Predominantly intracellular IL-37 downregulates liver inflammation and fibrosis. The correlation of serum IL-37 with disease severity in cirrhosis suggests its potential as a novel target modulating the course of liver fibrosis

Risk of Stroke before Revascularisation in Patients with Symptomatic Carotid Stenosis: A Pooled Analysis of Randomised Controlled Trials.

OBJECTIVE: Current guidelines recommending rapid revascularisation of symptomatic carotid stenosis are largely based on data from clinical trials performed at a time when best medical therapy was potentially less effective than today. The risk of stroke and its predictors among patients with symptomatic carotid stenosis awaiting revascularisation in recent randomised controlled trials (RCTs) and in medical arms of earlier RCTs was assessed. METHODS: The pooled data of individual patients with symptomatic carotid stenosis randomised to stenting (CAS) or endarterectomy (CEA) in four recent RCTs, and of patients randomised to medical therapy in three earlier RCTs comparing CEA vs. medical therapy, were compared. The primary outcome event was any stroke occurring between randomisation and treatment by CAS or CEA, or within 120 days after randomisation. RESULTS: A total of 4 754 patients from recent trials and 1 227 from earlier trials were included. In recent trials, patients were randomised a median of 18 (IQR 7, 50) days after the qualifying event (QE). Twenty-three suffered a stroke while waiting for revascularisation (cumulative 120 day risk 1.97%, 95% confidence interval [CI] 0.75 - 3.17). Shorter time from QE until randomisation increased stroke risk after randomisation (χ2 = 6.58, p = .011). Sixty-one patients had a stroke within 120 days of randomisation in the medical arms of earlier trials (cumulative risk 5%, 95% CI 3.8 - 6.2). Stroke risk was lower in recent than earlier trials when adjusted for time between QE and randomisation, age, severity of QE, and degree of carotid stenosis (HR 0.47, 95% CI 0.25 - 0.88, p = .019). CONCLUSION: Patients with symptomatic carotid stenosis enrolled in recent large RCTs had a lower risk of stroke after randomisation than historical controls. The added benefit of carotid revascularisation to modern medical care needs to be revisited in future studies. Until then, adhering to current recommendations for early revascularisation of patients with symptomatic carotid stenosis considered to require invasive treatment is advisable

Early Endarterectomy Carries a Lower Procedural Risk Than Early Stenting in Patients With Symptomatic Stenosis of the Internal Carotid Artery: Results From 4 Randomized Controlled Trials.

Patients undergoing carotid endarterectomy (CEA) for symptomatic stenosis of the internal carotid artery benefit from early intervention. Heterogeneous data are available on the influence of timing of carotid artery stenting (CAS) on procedural risk. We investigated the association between timing of treatment (0-7 days and >7 days after the qualifying neurological event) and the 30-day risk of stroke or death after CAS or CEA in a pooled analysis of individual patient data from 4 randomized trials by the Carotid Stenosis Trialists' Collaboration. Analyses were done per protocol. To obtain combined estimates, logistic mixed models were applied. Among a total of 4138 patients, a minority received their allocated treatment within 7 days after symptom onset (14% CAS versus 11% CEA). Among patients treated within 1 week of symptoms, those treated by CAS had a higher risk of stroke or death compared with those treated with CEA: 8.3% versus 1.3%, risk ratio, 6.7; 95% confidence interval, 2.1 to 21.9 (adjusted for age at treatment, sex, and type of qualifying event). For interventions after 1 week, CAS was also more hazardous than CEA: 7.1% versus 3.6%, adjusted risk ratio, 2.0; 95% confidence interval, 1.5 to 2.7 (P value for interaction with time interval 0.06). In randomized trials comparing stenting with CEA for symptomatic carotid artery stenosis, CAS was associated with a substantially higher periprocedural risk during the first 7 days after the onset of symptoms. Early surgery is safer than stenting for preventing future stroke. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00190398; URL: http://www.controlled-trials.com. Unique identifier: ISRCTN57874028; URL: http://www.controlled-trials.com. Unique identifier: ISRCTN25337470; URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004732

An Experimental and Numerical Investigation of Flapping-Wing Propulsion

AIAA Paper No. 99-0995, 37th AIAA Aerospace Sciences Meeting, Reno, Nevada, Jan. 1999.Flapping-wing propulsion is investigated experimentally and numerically with direct comparisons between experimental and numerical thrust measurements for several geometrically simple configurations. Numerical simulations are performed using linear theory, and a previously developed, unsteady panel method that models one or two independently moving airfoils with three-degrees of freedom and non-linear deforming wakes. Experiments are carried out in the Naval Postgraduate School 5'×5' low-speed tunnel. A flapping mechanism that approximates the two-dimensional motions modeled by the panel code is suspended with cables in the wind tunnel, and thrust measurements are made by measuring the streamwise displacement of the model using a laser range-finder. The experimental flapping mechanism utilizes variable aspect-ratio wings and optional tip plates to investigate the effect of three-dimensionality. The device flaps two airfoils, each with two degrees of freedom and adjustable pitch and plunge amplitudes, and additional stationary wings may be attached up and/or downstream of the flapping wings to investigate interference effects

Endovascular therapy versus no endovascular therapy in patients receiving best medical management for acute isolated occlusion of the posterior cerebral artery : A systematic review and meta-analysis

Background and purpose Endovascular therapy (EVT) is increasingly reported for treatment of isolated posterior cerebral artery (PCA) occlusions although its clinical benefit remains uncertain. This study-level meta-analysis investigated the functional outcomes and safety of EVT and best medical management (BMM) compared to BMM alone for treatment of PCA occlusion stroke. Methods We conducted a literature search in PubMed, Web of Science and Embase for studies in patients with isolated PCA occlusion stroke treated with EVT + BMM or BMM including intravenous thrombolysis. There were no randomized trials and all studies were retrospective. The primary outcome was modified Rankin Scale score of 0-2 at 3 months, while safety outcomes included mortality rate and incidence of symptomatic intracranial hemorrhage (sICH). Results Twelve studies with a total of 679 patients were included in the meta-analysis: 338 patients with EVT + BMM and 341 patients receiving BMM alone. Good functional outcome at 3 months was achieved in 58.0% (95% confidence interval [CI] 43.83-70.95) of patients receiving EVT + BMM and 48.1% (95% CI 40.35-55.92) of patients who received BMM alone, with respective mortality rates of 12.6% (95% CI 7.30-20.93) and 12.3% (95% CI 8.64-17.33). sICH occurred in 4.2% (95% CI 2.47-7.03) of patients treated with EVT + BMM and 3.2% (95% CI 1.75-5.92) of patients treated with BMM alone. Comparative analyses were performed on studies that included both treatments and these demonstrated no significant differences. Conclusions Our results demonstrate that EVT represents a safe treatment for patients with isolated PCA occlusion stroke. There were no differences in clinical or safety outcomes between treatments, supporting randomization of future patients into distal vessel occlusion trials.Peer reviewe

Prediction Models for Clinical Outcome After a Carotid Revascularization Procedure.

Background and Purpose- Prediction models may help physicians to stratify patients with high and low risk for periprocedural complications or long-term stroke risk after carotid artery stenting or carotid endarterectomy. We aimed to evaluate external performance of previously published prediction models for short- and long-term outcome after carotid revascularization in patients with symptomatic carotid artery stenosis. Methods- From a literature review, we selected all prediction models that used only readily available patient characteristics known before procedure initiation. Follow-up data from 2184 carotid artery stenting and 2261 carotid endarterectomy patients from 4 randomized trials (EVA-3S [Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis], SPACE [Stent-Protected Angioplasty Versus Carotid Endarterectomy], ICSS [International Carotid Stenting Study], and CREST [Carotid Revascularization Endarterectomy Versus Stenting Trial]) were used to validate 23 short-term outcome models to estimate stroke or death risk ≤30 days after the procedure and the original outcome measure for which the model was developed. Additionally, we validated 7 long-term outcome models for the original outcome measure. Predictive performance of the models was assessed with C statistics and calibration plots. Results- Stroke or death ≤30 days after the procedure occurred in 158 (7.2%) patients after carotid artery stenting and in 84 (3.7%) patients after carotid endarterectomy. Most models for short-term outcome after carotid artery stenting (n=4) or carotid endarterectomy (n=19) had poor discriminative performance (C statistics ranging from 0.49-0.64) and poor calibration with small absolute risk differences between the lowest and highest risk groups and overestimation of risk in the highest risk groups. Long-term outcome models (n=7) had a slightly better performance with C statistics ranging from 0.59 to 0.67 and reasonable calibration. Conclusions- Current models did not reliably predict outcome after carotid revascularization in a trial population of patients with symptomatic carotid stenosis. In particular, prediction of short-term outcome seemed to be difficult. Further external validation of existing prediction models or development of new prediction models is needed before such models can be used to support treatment decisions in individual patients