Contralateral Stenosis and Echolucent Plaque Morphology are Associated with Elevated Stroke Risk in Patients Treated with Asymptomatic Carotid Artery Stenosis within a Controlled Clinical Trial (SPACE-2).

BACKGROUND: Asymptomatic carotid artery stenosis (ACS) has a low risk of stroke. To achieve an advantage over noninterventional best medical treatment (BMT), carotid endarterectomy (CEA) or carotid artery stenting (CAS) must be performed with the lowest possible risk of stroke. Therefore, an analysis of risk-elevating factors is essential. Grade of ipsilateral and contralateral stenosis as well as plaque morphology are known risk factors in ACS. METHODS: The randomized, controlled, multicenter SPACE-2 trial had to be stopped prematurely after recruiting 513 patients. 203 patients were randomized to CEA, 197 to CAS, and 113 to BMT. Within one year, risk factors such as grade of stenosis and plaque morphology were analyzed. RESULTS: Grade of contralateral stenosis (GCS) was higher in patients with any stroke (50%ECST vs. 20%ECST; p=0.012). Echolucent plaque morphology was associated with any stroke on the day of intervention (OR 5.23; p=0.041). In the periprocedural period, any stroke was correlated with GCS in the CEA group (70%ECST vs. 20%ECST; p=0.026) and with echolucent plaque morphology in the CAS group (6% vs. 1%; p=0.048). In multivariate analysis, occlusion of the contralateral carotid artery (CCO) was associated with risk of any stroke (OR 7.00; p=0.006), without heterogeneity between CEA and CAS. CONCLUSION: In patients with asymptomatic carotid artery stenosis, GCS, CCO, as well as echolucent plaque morphology were associated with a higher risk of cerebrovascular events. The risk of stroke in the periprocedural period was increased by GCS in CEA and by echolucent plaque in CAS. Due to small sample size, results must be interpreted carefully.

Oral anticoagulation in patients with atrial fibrillation and acute ischaemic stroke: design and baseline data of the prospective multicentre Berlin Atrial Fibrillation Registry.

AIMS: The Berlin Atrial Fibrillation Registry was designed to analyse oral anticoagulation (OAC) prescription in patients with atrial fibrillation (AF) and acute ischaemic stroke. METHODS AND RESULTS: This investigator-initiated prospective multicentre registry enrolled patients at all 16 stroke units located in Berlin, Germany. The ongoing telephone follow-up is conducted centrally and will cover 5 years per patient. Within 2014 and 2016, 1080 patients gave written informed consent and 1048 patients were available for analysis. Median age was 77 years [interquartile range (IQR) 72-83], 503 (48%) patients were female, and 254 (24%) had a transient ischaemic attack (TIA). Overall, 470 (62%) out of 757 patients with known AF and a (pre-stroke) CHA2DS2-VASc ≥ 1 were anticoagulated at the time of stroke. At hospital discharge, 847 (81.3%) of 1042 patients were anticoagulated. Thereof 710 (68.1%) received a non-vitamin K-dependent oral anticoagulant (NOAC) and 137 (13.1%) a vitamin K antagonist (VKA). Pre-stroke intake of a NOAC [odds ratio (OR) 15.6 (95% confidence interval, 95% CI 1.97-122)] or VKA [OR 0.04 (95% CI 0.02-0.09)], an index TIA [OR 0.56 (95% CI 0.34-0.94)] rather than stroke, heart failure [OR 0.49 (95% CI 0.26-0.93)], and endovascular thrombectomy at hospital admission [OR 12.9 (95% CI 1.59-104)] were associated with NOAC prescription at discharge. Patients' age or AF type had no impact on OAC or NOAC use, respectively. CONCLUSION: About 60% of all registry patients with known AF received OAC at the time of stroke or TIA. At hospital discharge, more than 80% of AF patients were anticoagulated and about 80% of those were prescribed a NOAC.

Heart failure, recurrent vascular events and death in patients with ischemic stroke-results of the MonDAFIS study.

Heart failure (HF) is associated with poor outcome after stroke, but data from large prospective trials are sparse.We assessed the impact of HF on clinical endpoints in patients hospitalized with acute ischemic stroke or transient ischemic attack (TIA) enrolled in the prospective, multicenter Systematic Monitoring for Detection of Atrial Fibrillation in Patients with Acute Ischemic Stroke (MonDAFIS) trial. HF was defined as left ventricular ejection fraction (LVEF) < 55% or a history of HF on admission. The composite of recurrent stroke, major bleeding, myocardial infarction, and all-cause death, and its components during the subsequent 24 months were assessed. We used estimated hazard ratios in confounder-adjusted models. Overall, 410/2562 (16.0%) stroke patients fulfilled the HF criteria (i.e. 381 [14.9%] with LVEF < 55% and 29 [1.9%] based on medical history). Patients with HF had more often diabetes, coronary and peripheral arterial disease and presented with more severe strokes on admission. HF at baseline correlated with myocardial infarction (HR 2.21; 95% CI 1.02-4.79), and all-cause death (HR 1.67; 95% CI 1.12-2.50), but not with major bleed (HR 1.93; 95% CI 0.73-5.06) or recurrent stroke/TIA (HR 1.08; 95% CI 0.75-1.57). The data were adjusted for age, stroke severity, cardiovascular risk factors, and randomization. Patients with ischemic stroke or TIA and comorbid HF have a higher risk of myocardial infarction and death compared with non-HF patients whereas the risk of recurrent stroke or major hemorrhage was similar. Trial registration number Clinicaltrials.gov NCT02204267.

Carotid endarterectomy or stenting or best medical treatment alone for moderate-to-severe asymptomatic carotid artery stenosis: 5-year results of a multicentre, randomised controlled trial.

BACKGROUND: The optimal treatment for patients with asymptomatic carotid artery stenosis is under debate. Since best medical treatment (BMT) has improved over time, the benefit of carotid endarterectomy (CEA) or carotid artery stenting (CAS) is unclear. Randomised data comparing the effect of CEA and CAS versus BMT alone are absent. We aimed to directly compare CEA plus BMT with CAS plus BMT and both with BMT only. METHODS: SPACE-2 was a multicentre, randomised, controlled trial at 36 study centres in Austria, Germany, and Switzerland. We enrolled participants aged 50-85 years with asymptomatic carotid artery stenosis at the distal common carotid artery or the extracranial internal carotid artery of at least 70%, according to European Carotid Surgery Trial criteria. Initially designed as a three-arm trial including one group for BMT alone (with a randomised allocation ratio of 2·9:2·9:1), the SPACE-2 study design was amended (due to slow recruitment) to become two substudies with two arms each comparing CEA plus BMT with BMT alone (SPACE-2a) and CAS plus BMT with BMT alone (SPACE-2b); in each case in a 1:1 randomisation. Participants and clinicians were not masked to allocation. The primary efficacy endpoint was the cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years. The primary safety endpoint was any stroke or death from any cause within 30 days after CEA or CAS. The primary analysis was by intention-to treat, which included all randomly assigned patients in SPACE-2, SPACE-2a, and SPACE-2b, analysed using meta-analysis of individual patient data. We did two-step hierarchical testing to first show superiority of CEA and CAS to BMT alone then to assess non-inferiority of CAS to CEA. Originally, we planned to recruit 3640 patients; however, the study had to be stopped prematurely due to insufficient recruitment. This report presents the primary analysis at 5-year follow-up. This trial is registered with ISRCTN, number ISRCTN78592017. FINDINGS: 513 patients across SPACE-2, SPACE-2a, and SPACE-2b were recruited and surveyed between July 9, 2009, and Dec 12, 2019, of whom 203 (40%) were allocated to CEA plus BMT, 197 (38%) to CAS plus BMT, and 113 (22%) to BMT alone. Median follow-up was 59·9 months (IQR 46·6-60·0). The cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years (primary efficacy endpoint) was 2·5% (95% CI 1·0-5·8) with CEA plus BMT, 4·4% (2·2-8·6) with CAS plus BMT, and 3·1% (1·0-9·4) with BMT alone. Cox proportional-hazard testing showed no difference in risk for the primary efficacy endpoint for CEA plus BMT versus BMT alone (hazard ratio [HR] 0·93, 95% CI 0·22-3·91; p=0·93) or for CAS plus BMT versus BMT alone (1·55, 0·41-5·85; p=0·52). Superiority of CEA or CAS to BMT was not shown, therefore non-inferiority testing was not done. In both the CEA group and the CAS group, five strokes and no deaths occurred in the 30-day period after the procedure. During the 5-year follow-up period, three ipsilateral strokes occurred in both the CAS plus BMT and BMT alone group, with none in the CEA plus BMT group. INTERPRETATION: CEA plus BMT or CAS plus BMT were not found to be superior to BMT alone regarding risk of any stroke or death within 30 days or ipsilateral stroke during the 5-year observation period. Because of the small sample size, results should be interpreted with caution. FUNDING: German Federal Ministry of Education and Research (BMBF) and German Research Foundation (DFG).

Off-label-dosing of non-vitamin K-dependent oral antagonists in AF patients before and after stroke: results of the prospective multicenter Berlin Atrial Fibrillation Registry.

AIMS: We aimed to analyze prevalence and predictors of NOAC off-label under-dosing in AF patients before and after the index stroke. METHODS: The post hoc analysis included 1080 patients of the investigator-initiated, multicenter prospective Berlin Atrial Fibrillation Registry, designed to analyze medical stroke prevention in AF patients after acute ischemic stroke. RESULTS: At stroke onset, an off-label daily dose was prescribed in 61 (25.5%) of 239 NOAC patients with known AF and CHA2DS2-VASc score ≥ 1, of which 52 (21.8%) patients were under-dosed. Under-dosing was associated with age ≥ 80 years in patients on rivaroxaban [OR 2.90, 95% CI 1.05-7.9, P = 0.04; n = 29] or apixaban [OR 3.24, 95% CI 1.04-10.1, P = 0.04; n = 22]. At hospital discharge after the index stroke, NOAC off-label dose on admission was continued in 30 (49.2%) of 61 patients. Overall, 79 (13.7%) of 708 patients prescribed a NOAC at hospital discharge received an off-label dose, of whom 75 (10.6%) patients were under-dosed. Rivaroxaban under-dosing at discharge was associated with age ≥ 80 years [OR 3.49, 95% CI 1.24-9.84, P = 0.02; n = 19]; apixaban under-dosing with body weight ≤ 60 kg [OR 0.06, 95% CI 0.01-0.47, P < 0.01; n = 56], CHA2DS2-VASc score [OR per point 1.47, 95% CI 1.08-2.00, P = 0.01], and HAS-BLED score [OR per point 1.91, 95% CI 1.28-2.84, P < 0.01]. CONCLUSION: At stroke onset, off-label dosing was present in one out of four, and under-dosing in one out of five NOAC patients. Under-dosing of rivaroxaban or apixaban was related to old age. In-hospital treatment after stroke reduced off-label NOAC dosing, but one out of ten NOAC patients was under-dosed at discharge. CLINICAL TRIAL REGISTRATION: NCT02306824.

The importance of size: successful recanalization by intravenous thrombolysis in acute anterior stroke depends on thrombus length.

BACKGROUND AND PURPOSE: We hypothesize that in acute middle cerebral artery stroke, thrombus lengths measured in thin-slice nonenhanced CT images define a limit beyond which systemic thrombolysis will fail to recanalize occluded arteries. METHODS: In 138 patients who presented with acute middle cerebral artery stroke and who were treated with intravenous thrombolysis (IVT), we measured lengths of thrombotic clots depicted as arterial hyperdensities in admission nonenhanced CT images with 2.5-mm slice width. Vascular recanalization was investigated after thrombolysis and recanalization results were related to thrombus lengths by logistic regression. RESULTS: In 62 patients, IVT resulted in recanalization; among these patients, no thrombus length exceeded 8 mm. The median modified Rankin scale score at hospital discharge was 2. In the remaining 76 patients, thrombus lengths mostly exceeded 8 mm and IVT failed in recanalization. These patients were discharged with a median modified Rankin scale score of 5. CONCLUSIONS: This study shows that in acute middle cerebral artery stroke, IVT has nearly no potential to recanalize occluded vessels if thrombus length exceeds 8 mm.

Complication rate in unprotected carotid artery stenting with closed-cell stents.

INTRODUCTION: The discussion on the use of protection devices (PDs) in carotid artery stenting (CAS) is gaining an increasing role in lowering the periprocedural complication rates. While many reviews and reports with retrospective data analysis do promote the use of PDs the most recent multi-centre trials are showing advantages for unprotected CAS combined with closed-cell stent designs. METHODS: We retrospectively analysed 358 unprotected CAS procedures performed from January 2003 to June 2009 in our clinic. Male/female ratio was 2.68/1. The average age was 69.3 years. Seventy-three percent (261/358) showed initial neurological symptoms. All patients were treated on a standardised interventional protocol. A closed and small-sized cell designed stent was implanted in most cases (85.2%). One hundred seventy-one (47.8%) were controlled by Doppler ultrasonography usually at first in a 3-month and later in 6-month intervals. RESULTS: The peri-interventional and 30-day mortality/stroke rate was 4.19% (15/358). These events included three deaths, five hyperperfusion syndromes (comprising one death by a secondary fatal intracranial haemorrhage), one subarachnoid haemorrhage and seven ischaemic strokes. Only 20% (3/15) of all complications occurred directly peri-interventional. The overall peri-interventional complication rate was 0.8% (3/358). Most complications occurred in initial symptomatic patients (5.36%). The in-stent restenosis rate for more than 70% was 7% (12/171) detected at an average of 9.8 month. CONCLUSION: Our clinical outcome demonstrates that unprotected CAS with small cell designed stents results in a very low procedural complication rate, which makes the use of a protection device dispensable.

Subacute stent thrombosis in intracranial stenting.

BACKGROUND AND PURPOSE: We sought to determine the safety of intracranial stenting with respect to subacute stent thrombosis in patients being treated with standardized antiplatelet therapy. METHODS: We retrospectively evaluated the outcome of primary intracranial stenting of atherosclerotic stenoses and of stenting in coil embolization procedures in 67 patients. We focused on those cases that led to subacute stent thrombosis even though the patients had been treated with standardized antiplatelet therapy before, during, and after stent placement. Patient age ranged from 19 to 78 years. In 33 patients, stents were placed for treatment of atherosclerotic stenoses; in the remaining 34 patients, stents were placed to assist coiling of aneurysms. The patients in this study were treated between January 2003 and August 2007. RESULTS: Of the total 67 patients initially treated successfully by intracranial stenting, 7 patients developed subacute stent thrombosis. Of these 7 patients, 3 received stent placement into the basilar artery because of an underlying stenosis; in 1 patient, a stenosis of the M1 segment of the middle cerebral artery was treated. In 3 patients, aneurysms of the anterior cerebral artery, the posterior inferior cerebellar artery, and the basilar artery were treated by stent-assisted coil embolization. In 4 of the 7 patients with subacute thrombosis, recanalization of stents by local application of recombinant tissue-type plasminogen activator was successful. CONCLUSIONS: Intracranial stenting can lead to subacute stent thrombosis, even in patients who are treated with standardized antiplatelet therapy. Such complications have been described for patients after coronary artery stenting, but to our knowledge, no one has reported on a comparable number of cases of intracranial stenting procedures. In certain clinical scenarios, local thrombolysis with recombinant tissue-type plasminogen activator is an important treatment option to deal with subacute stent thrombosis.

To stent or not to stent: stent-protected percutaneous angioplasty versus endarterectomy post hoc analyses.

PURPOSE OF REVIEW: To summarize randomized controlled trials on endarterectomy and stenting of symptomatic carotid stenoses and identify factors that impact the decision for either therapeutic method. RECENT FINDINGS: Carotid endarterectomy is currently the standard method of secondary stroke prevention in patients with moderate-to-severe symptomatic carotid artery stenosis. Carotid artery stenting has emerged as a therapeutic alternative. The noninferiority to endarterectomy with respect to periprocedural safety has not been proven, but the long-term efficiency of stroke prevention after successful stenting is very similar, despite the observation that the rate of restenosis after stenting is significantly higher than after endarterectomy. Thus, the key difference between stenting and surgery is periprocedural safety. From subgroup analysis of the Stent-protected Percutaneous Angioplasty versus Endarterectomy data, it emerges that elderly patients are at higher than average periprocedural risk of ipsilateral stroke on the day of stenting but not if treated by surgery. This finding is an argument for catheter access problems through tortuous vessels with severe atherosclerosis in the proximal carotid artery of elderly patients as the source of periprocedural risk of stenting. SUMMARY: Carotid artery stenting for secondary stroke prevention is a method with unproven noninferiority of periprocedural safety but similar long-term efficiency compared to endarterectomy.

Association of right-to-left shunt with frontal white matter lesions in T2-weighted MR imaging of stroke patients.

INTRODUCTION: Cardiac right-to-left shunt (RLS), mainly due to patent foramen ovale (PFO), is a risk factor for paradoxical embolism and stroke. Results of studies about brain lesions in diffusion-weighted imaging (DWI) in PFO patients were controversial. DWI only detects acute ischemic lesions. We assessed the hypothesis that, in T2-weighted magnetic resonance imaging (T2WI) of stroke patients, RLS is associated with a typical distribution of small white matter lesions. MATERIALS AND METHODS: In this retrospective case-control study, T2WI images of 162 stroke patients were evaluated. From stroke patients admitted between 1999 and 2003, 81 stroke patients with RLS were identified with contrast-enhanced transcranial Doppler (bubble test). Controls were 81 age-matched stroke patients without RLS (negative bubble test). In T2WI images, small lesions (<2 cm) were categorized depending on their location in subcortical white matter, peritrigonal white matter, deep and paraventricular white matter, and basal ganglia. Additionally, larger territorial infarcts were rated. RESULTS: In T2WI frontal or predominantly frontal-located subcortical small white matter, lesions are significantly associated with RLS (p < 0.0001, chi-square test). Forty-three patients with RLS (53%) and only 19 control patients (23%) showed this frontal dominance. Odds ratio is 3.7 (95% confidence interval = 1.9-7.1) for having a RLS when T2WI shows this lesion pattern in a stroke patient. No patient of the RLS group and 6% of the control group had parietal dominance. Distribution of small lesions in other locations like basal ganglia or deep white matter showed no significant difference for the groups. CONCLUSION: A distribution of mainly frontal subcortical small white matter lesions in T2WI is significantly associated with RLS in stroke patients.

Results of the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) study to treat symptomatic stenoses at 2 years: a multinational, prospective, randomised trial.

BACKGROUND: The SPACE trial is a multinational, prospective, randomised study to test the hypothesis that carotid artery stenting is not inferior to carotid endarterectomy for treating patients with severe symptomatic carotid artery stenosis. We did not prove non-inferiority of carotid artery stenting compared with carotid endarterectomy for the 30-day complication rate, and we now report the results at 2 years. METHODS: Between March, 2001, and February, 2006, patients with symptomatic, severe (>or=70%) carotid artery stenosis were recruited to this non-inferiority trial and randomly assigned with a block randomisation design to have carotid artery angioplasty with stenting or carotid artery endarterectomy. 2-year endpoints include several clinical endpoints and the incidence of recurrent carotid stenosis of at least 70%. Clinical and vascular follow-up was done by a certified neurologist. Analyses were by intention to treat and per protocol. This trial is registered with ISRCTN, number 57874028.12. FINDINGS: 1 214 patients were randomly assigned (613 were randomly assigned to carotid angioplasty with stenting and 601 were randomly assigned to carotid endarterectomy). In both the intention-to-treat and per-protocol analyses the Kaplan-Meier estimates of ipsilateral ischaemic strokes up to 2 years after the procedure and any periprocedural stroke or death do not differ between the carotid artery stenting and the carotid endarterectomy groups (intention to treat 9.5%vs 8.8%; hazard ratio (HR) 1.10, 95%CI 0.75 to 1.61; log-rank p=0.62; per protocol 9.4%vs 7.8%; HR 1.23, 95%CI 0.82 to 1.83; log-rank p=0.31). In both the intention-to-treat and per-protocol populations, recurrent stenosis of 70% or more is significantly more frequent in the carotid artery stenting group compared with the carotid endarterectomy group, with a life-table estimate of 10.7% versus 4.6% (p=0.0009) and 11.1% versus 4.6% (p=0.0007), respectively. Only two incidences of recurrent stenoses after carotid artery stenting led to neurological symptoms. INTERPRETATION: After 2 years' follow-up, the rate of recurrent ipsilateral ischaemic strokes reported in the SPACE trial is similar for both treatment groups. The incidence of recurrent carotid stenosis at 2 years, as defined by ultrasound, is significantly higher after carotid artery stenting. However, it cannot be excluded that the degree of in-stent stenosis is slightly overestimated by conventional ultrasound criteria.

Clinical and angiographic risk factors for stroke and death within 30 days after carotid endarterectomy and stent-protected angioplasty: a subanalysis of the SPACE study.

BACKGROUND: Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are used to prevent ischaemic stroke in patients with stenosis of the internal carotid artery. Better knowledge of risk factors could improve assignment of patients to these procedures and reduce overall risk. We aimed to assess the risk of stroke or death associated with CEA and CAS in patients with different risk factors. METHODS: We analysed data from 1196 patients randomised to CAS or CEA in the Stent-Protected Angioplasty versus Carotid Endarterectomy in Symptomatic Patients (SPACE) trial. The primary outcome event was death or ipsilateral stroke (ischaemic or haemorrhagic) with symptoms that lasted more than 24 h between randomisation and 30 days after therapy. Six predefined variables were assessed as potential risk factors for this outcome: age, sex, type of qualifying event, side of intervention, degree of stenosis, and presence of high-grade contralateral stenosis or occlusion. The SPACE trial is registered at Current Controlled Trials, with the international standard randomised controlled trial number ISRCTN57874028. FINDINGS: Risk of ipsilateral stroke or death increased significantly with age in the CAS group (p=0.001) but not in the CEA group (p=0.534). Classification and regression tree analysis showed that the age that gave the greatest separation between high-risk and low-risk populations who had CAS was 68 years: the rate of primary outcome events was 2.7% (8/293) in patients who were 68 years old or younger and 10.8% (34/314) in older patients. Other variables did not differ between the CEA and CAS groups. INTERPRETATION: Of the predefined covariates, only age was significantly associated with the risk of stroke and death. The lower risk after CAS versus CEA in patients up to 68 years of age was not detectable in older patients. This finding should be interpreted with caution because of the drawbacks of post-hoc analyses.

Hemodynamic assessment of carotid stenosis by functional magnetic resonance imaging.

BACKGROUND: Functional magnetic resonance imaging (fMRI) is a method usually used to identify cortical representations of cerebral functions. Some studies and case reports suggest that stenoses of the brain-supplying arteries influence the BOLD (blood-oxygenation-level-dependent) signal. The objective of this study was to find out whether the BOLD signal differs in the ipsilateral hemisphere of patients with hemodynamically relevant and those with irrelevant stenosis of the internal carotid artery (ICA) and if a successful treatment might have an influence on the BOLD signal. METHODS: We included 10 patients with hemodynamically relevant stenosis in group 1; another 10 patients with hemodynamically irrelevant stenosis of the ICA were included in group 2. Patients underwent recanalization by either stenting or operation of the ICA. fMRI with a hand-tapping task was performed before and after treatment. Data were analyzed with 'Statistical Parametric Mapping' 2 for both hemispheres. An asymmetry index (AI, range 0-2) was calculated for the hand motor areas. RESULTS: All data are given as means +/- SD. The mean preinterventional AI in group 1 was 1.08 +/- 0.87 and 0.30 +/- 0.54 in group 2 (p = 0.029). The mean postinterventional AI was 0.32 +/- 0.29 in group 1 and 0.25 +/- 0.21 in group 2 (p = 0.599). CONCLUSION: fMRI is not only capable of delivering spatial information, but also of distinguishing a hemodynamically relevant from an irrelevant stenosis of the ICA.

Differences in complication rates among the centres in the SPACE study.

INTRODUCTION: Despite the high grade of standardisation of study protocols, there is still room for variability among the centres in specific treatment aspects. We evaluated the treatment risk in stent-protected angioplasty of the carotid versus endarterectomy (SPACE) associated with the specific patient enrollment rates of the centres. MATERIALS AND METHODS: The analysed endpoints were ipsilateral stroke or death [primary outcome event (pOE)] and any stroke or death [secondary outcome event (sOE)] until 30 days after treatment. A binary logistic regression analysis with random effects was performed separately for each treatment arm. The centres were secondarily categorised in three classes: I) > or = 25 patients enrolled, II) ten to 24 patients and III) <10 patients and a hierarchic log linear model was fitted to test the three-way interaction of treatment, number of patients per class and outcome. RESULTS: The random effects logistic regression analysis in the carotid artery stenting (CAS) arm proved a significant increase in pOE with decreasing number of patients enrolled (-0.0190 +/- 0.0085, p = 0.025, deviance 35.7 with 32 df), whereas no such effect was found in the carotid endartectomy (CEA) arm (-0.010 +/- 0.008, p = 0.24, deviance 39.78 with 32 df). In the log linear model, there was a significant interaction between treatment, number of patients per centre and sOE (p = 0.023). The odds ratios for sOE in the enrollment classes (CAS vs. CEA) were 0.98 (95% CI 0.50-1.94, p = 0.95) for class I, 1.13 (95% CI 0.47-2.77, p = 0.77) for class II and 11.56 (95% CI 1.40-253.45, p = 0.01) for class III centres. CONCLUSION: Despite rigorous standardisation and quality requirements for operator qualification, there seemed to be a decrease in complication rate with increasing patient enrollment numbers in the CAS arm while this signal could not be detected in the CEA arm of SPACE.

The POST trial: initial post-market experience of the Penumbra system: revascularization of large vessel occlusion in acute ischemic stroke in the United States and Europe.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the initial post-market experience of the device and how it is compared with the Penumbra Pivotal trial used to support the 510k application. METHODS: A retrospective case review of 157 consecutive patients treated with the Penumbra system at seven international centers was performed. Primary endpoints were revascularization of the target vessel (TIMI score of 2 or 3), good functional outcome as defined by a modified Rankin scale (mRS) score of ≤2 and incidence of procedural serious adverse events. Results were compared with those of the Penumbra pivotal trial. RESULTS: A total of 157 vessels were treated. Mean baseline values at enrollment were: age 65 years, NIHSS score 16. After use of the Penumbra system, 87% of the treated vessels were revascularized to TIMI 2 (54%) or 3 (33%) as compared with 82% reported in the Pivotal trial. Nine procedural serious adverse events were reported in 157 patients (5.7%). All-cause mortality was 20% (32/157), and 41% had a mRS of ≤2 at 90-day follow-up as compared with only 25% in the Pivotal trial. Patients who were successfully revascularized by the Penumbra system had significantly better outcomes than those who were not. CONCLUSION: Initial post-market experience of the Penumbra system revealed that the revascularization rate and safety profile of the device are comparable to those reported in the Pivotal trial. However, the proportion of patients who had good functional outcome was higher than expected.

Neuropsychological consequences of endarterectomy and endovascular angioplasty with stent placement for treatment of symptomatic carotid stenosis: a prospective randomised study.

BACKGROUND AND PURPOSE: Previous studies compared carotid endarterectomy (CEA) and carotid artery stent placement (CAS) for treatment of symptomatic carotid artery stenosis. Whereas most previous studies showed both treatment modalities to be associated with a comparable risk of periprocedural cerebrovascular complications, these previous studies have shown significantly more microemboli and significantly more lesions in diffusion-weighted MR imaging after CAS compared to CEA. The clinical relevance of these differences remains unknown. We therefore compared the neuropsychological consequences of CAS and CEA and additionally measured the S100beta protein, a marker of cerebral damage. METHODS: A total of 48 patients with symptomatic carotid artery stenosis greater than 70 % (according to ECST criteria) were enrolled and 45 patients participated in the follow-up. The patients were randomly assigned for CEA (24 patients) or CAS (21 patients). S100beta protein values were evaluated 2 hours before the procedure, as well as one and two hours thereafter. Patients were assessed before treatment, and again 6 and 30 days after treatment using a comprehensive neuropsychological test battery. RESULTS: Patients of the CAS and the CEA groups did not significantly differ in terms of age, gender, education, degree of carotid artery stenosis, cerebrovascular symptoms and vascular risk factors. Following previously used criteria, a cognitive change in patients was assumed to have occurred when there was a decline of more than one standard deviation in two or more tests assessing various cognitive domains. Six days and 30 days after the treatment both groups showed a comparable number of patients with cognitive changes compared to baseline. There were no significant differences in S100beta protein values. CONCLUSION: These results provide some reassurance that CAS is not associated with greater cognitive deterioration than CEA is.

Harlequin syndrome--one face of many etiologies.

BACKGROUND: A 55-year-old woman presented to hospital with a 3-month history of asymmetric facial flushing of the skin during exertion, and an 18-month history of left-sided ptosis and miosis. Detailed medical history analysis revealed that a palpable node measuring 0.8 x 1.2 x 1.2 cm (volume 1.1 ml) had been discovered 2 years previously, within the left lobe of an otherwise uncomplicated goiter that had been successfully managed for 20 years. Otherwise, the patient was healthy. INVESTIGATIONS: Neurological examination, autonomic testing, duplex ultrasonography, scintigraphy and MRI. DIAGNOSIS: Harlequin syndrome following a lesion of the preganglionic sympathetic efferents, caused by neurovascular compression of the sympathetic chain between the stellate and superior cervical ganglion brought about by an elongated inferior thyroid artery. MANAGEMENT: Explanation of pathophysiology and benign nature of the condition.

Evidence and consensus based guideline for the management of delirium, analgesia, and sedation in intensive care medicine. Revision 2015 (DAS-Guideline 2015) - short version.

In 2010, under the guidance of the DGAI (German Society of Anaesthesiology and Intensive Care Medicine) and DIVI (German Interdisciplinary Association for Intensive Care and Emergency Medicine), twelve German medical societies published the "Evidence- and Consensus-based Guidelines on the Management of Analgesia, Sedation and Delirium in Intensive Care". Since then, several new studies and publications have considerably increased the body of evidence, including the new recommendations from the American College of Critical Care Medicine (ACCM) in conjunction with Society of Critical Care Medicine (SCCM) and American Society of Health-System Pharmacists (ASHP) from 2013. For this update, a major restructuring and extension of the guidelines were needed in order to cover new aspects of treatment, such as sleep and anxiety management. The literature was systematically searched and evaluated using the criteria of the Oxford Center of Evidence Based Medicine. The body of evidence used to formulate these recommendations was reviewed and approved by representatives of 17 national societies. Three grades of recommendation were used as follows: Grade "A" (strong recommendation), Grade "B" (recommendation) and Grade "0" (open recommendation). The result is a comprehensive, interdisciplinary, evidence and consensus-based set of level 3 guidelines. This publication was designed for all ICU professionals, and takes into account all critically ill patient populations. It represents a guide to symptom-oriented prevention, diagnosis, and treatment of delirium, anxiety, stress, and protocol-based analgesia, sedation, and sleep-management in intensive care medicine.