Ten Years of Improving Acute Stroke Management in a Metropolitan Area: A Population-Based Quantification of Quality Indicators.

BACKGROUND AND PURPOSE: Rapid access to acute stroke treatment improves clinical outcomes in patients with ischemic stroke. We aimed to shorten the time to admission and to acute stroke treatment for patients with acute stroke in the Hamburg metropolitan area by collaborative multilevel measures involving all hospitals with stroke units, the Emergency Medical Services (EMS), and health-care authorities. METHODS: In 2007, an area-wide stroke care quality project was initiated. The project included mandatory admission of all stroke patients in Hamburg exclusively to hospitals with stroke units, harmonized acute treatment algorithms among all hospitals, repeated training of the EMS staff, a multimedia educational campaign, and a mandatory stroke care quality monitoring system based on structured data assessment and quality indicators for procedural measures. We analyzed data of all patients with acute stroke who received inhospital treatment in the city of Hamburg during the evaluation period from the quality assurance database data and evaluated trends of key quality indicators over time. RESULTS: From 2007 to 2016, a total of 83,395 patients with acute stroke were registered. During this period, the proportion of patients admitted within ≤3 h from symptom onset increased over time from 27.8% in 2007 to 35.2% in 2016 (p < 0.001). The proportion of patients who received rapid thrombolysis (within ≤30 min after admission) increased from 7.7 to 54.1% (p < 0.001). CONCLUSIONS: Collaborative stroke care quality projects are suitable and effective to improve acute stroke care.

Association Between Adherence to Quality Indicators and 7-Day In-Hospital Mortality After Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Quality indicators (QI) are an accepted tool to measure performance of hospitals in routine care. We investigated the association between quality of acute stroke care defined by overall adherence to evidence-based QI and early outcome in German acute care hospitals. METHODS: Patients with ischemic stroke admitted to one of the hospitals cooperating within the ADSR (German Stroke Register Study Group) were analyzed. The ADSR is a voluntary network of 9 regional stroke registers monitoring quality of acute stroke care across 736 hospitals in Germany. Quality of stroke care was defined by adherence to 11 evidence-based indicators of early processes of stroke care. The correlation between overall adherence to QI with outcome was investigated by assessing the association between 7-day in-hospital mortality with the proportion of QI fulfilled from the total number of QI the individual patient was eligible for. Generalized linear mixed model analysis was performed adjusted for the variables age, sex, National Institutes of Health Stroke Scale and living will and as random effect for the variable hospital. RESULTS: Between 2015 and 2016, 388 012 patients with ischemic stroke were reported (median age 76 years, 52.4% male). Adherence to distinct QI ranged between 41.0% (thrombolysis in eligible patients) and 95.2% (early physiotherapy). Seven-day in-hospital mortality was 3.4%. The overall proportion of QI fulfilled was median 90% (interquartile range, 75%-100%). In multivariable analysis, a linear association between overall adherence to QI and 7-day in-hospital-mortality was observed (odds ratio adherence <50% versus 100%, 12.7 [95% CI, 11.8-13.7]; P<0.001). CONCLUSIONS: Higher quality of care measured by adherence to a set of evidence-based process QI for the early phase of stroke treatment was associated with lower in-hospital mortality.

[Quality of life and disability after severe stroke and early neurological rehabilitation]. / Lebensqualität und Behinderung nach schwerem Schlaganfall und neurologischer Frührehabilitation.

BACKGROUND: Data on the long-term effects on quality of life of patients after severe stroke and discharge from early institutional rehabilitation are important for guiding the early rehabilitation phase and the further outpatient care. OBJECTIVE: Analysis of the outcome of patients following severe stroke 3 and 12 months after discharge from early neurological rehabilitation. METHODS: Analysis of the Asklepios Hamburg multicenter early stroke rehabilitation registry (ICD 10: I61, I60, I63 and OPS 8­552). Structured interviews with documentation of disabilities using the early rehabilitation Barthel index (ERBI), modified Rankin scale (mRS) and quality of life (12-item short form health survey, SF-12). Assessment of further treatment and complications 3 and 12 months after discharge from the early rehabilitation departments by telephone interviews. RESULTS: Out of 1045 treated stroke patients 270 were enrolled between October 2015 and November 2017 and 200 and 151 patients could be followed up after 3 and 12 months, respectively. There was a significant improvement (p < 0.001) in the median ERBI (151 patients at 12 months). Factors influencing a poorer functional outcome (higher mRS) at 12 months were a higher mRS at discharge (OR 5.43 [1.18, 25.09], p = 0.03) and age (per decade OR 1.5 [1.09, 2.02]; p = 0.01). Female sex reduced the risk for a poorer outcome after 12 months (OR 0.49 [0.25, 0.96]; p = 0.04). Quality of life (SF-12) was not different over time. The mental quality of life showed no differences (p = 0.32) compared to a historical, significantly less (p<0.001) handicapped stroke collective. CONCLUSION: The surviving severe stroke patients recovered significantly up to 12 months after discharge. The mental quality of life did not differ from that of a historical less handicapped collective.

Stroke unit care in germany: the german stroke registers study group (ADSR).

BACKGROUND: Factors influencing access to stroke unit (SU) care and data on quality of SU care in Germany are scarce. We investigated characteristics of patients directly admitted to a SU as well as patient-related and structural factors influencing adherence to predefined indicators of quality of acute stroke care across hospitals providing SU care. METHODS: Data were derived from the German Stroke Registers Study Group (ADSR), a voluntary network of 9 regional registers for monitoring quality of acute stroke care in Germany. Multivariable logistic regression analyses were performed to investigate characteristics influencing direct admission to SU. Generalized Linear Mixed Models (GLMM) were used to estimate the influence of structural hospital characteristics (percentage of patients admitted to SU, year of SU-certification, and number of stroke and TIA patients treated per year) on adherence to predefined quality indicators. RESULTS: In 2012 180,887 patients were treated in 255 hospitals providing certified SU care participating within the ADSR were included in the analysis; of those 82.4% were directly admitted to a SU. Ischemic stroke patients without disturbances of consciousness (p < .0001), an interval onset to admission time ≤3 h (p < .0001), and weekend admission (p < .0001) were more likely to be directly admitted to a SU. A higher proportion of quality indicators within predefined target ranges were achieved in hospitals with a higher proportion of SU admission (p = 0.0002). Quality of stroke care could be maintained even if certification was several years ago. CONCLUSIONS: Differences in demographical and clinical characteristics regarding the probability of SU admission were observed. The influence of structural characteristics on adherence to evidence-based quality indicators was low.

Safety of Endovascular Thrombectomy in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulants.

BACKGROUND AND PURPOSE: Prospective data on the safety of endovascular thrombectomy in acute stroke patients on non-vitamin K antagonist oral anticoagulants are lacking. METHODS: Prospective multicenter observational study. Patients with ischemic stroke undergoing thrombectomy with or without preceding thrombolysis were enrolled into the Registry of Acute Ischemic Stroke Under New Oral Anticoagulants. Baseline characteristics and functional outcome at 3 months were assessed. Hemorrhagic transformation and symptomatic intracranial hemorrhage were analyzed. Reperfusion was graded using the modified Thrombolysis in Cerebral Infarction score. RESULTS: Of 28 patients treated with thrombectomy, 5 had received also systemic thrombolysis (18%). Intracranial hemorrhage was observed in 46%, but symptomatic intracranial hemorrhage occurred only in 1 patient. Successful reperfusion (Thrombolysis in Cerebral Infarction score, 2b-3) was achieved in 59%. At 3 months, 19% had a modified Rankin Scale score of 0 to 2, and mortality was 26%. CONCLUSIONS: Thrombectomy in non-vitamin K antagonist oral anticoagulant patients seems safe although a comparatively high rate of asymptomatic hemorrhagic transformation was noted. Confirmation in larger prospective controlled cohorts is necessary. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01850797.

Gold- or Silver-Catalyzed Syntheses of Pyrones and Pyridine Derivatives: Mechanistic and Synthetic Aspects.

3-Oxo-5-alkynoic acid esters, on treatment with a carbophilic catalyst, undergo 6-endo-dig cyclization reactions to furnish either 2-pyrones or 4-pyrones in high yields. The regiochemical course can be dialed in by the proper choice of the alcohol part of the ester and the π-acid. This transformation is compatible with a variety of acid-sensitive groups as witnessed by a number of exigent applications to the total synthesis of natural products, including pseudopyronine A, hispidine, phellinin A, the radininol family, neurymenolide, violapyrone, wailupemycin and an unnamed brominated 4-pyrone of marine origin. Although the reaction proceeds well in neutral medium, the rate is largely increased when HOAc is used as solvent or co-solvent, which is thought to favor the protodeauration of the reactive alkenyl-gold intermediates as the likely rate-determining step of the catalytic cycle. Such intermediates are prone to undergo diauration as an off-cycle event that sequesters the catalyst; this notion is consistent with literature data and supported by the isolation of the gem-diaurated complexes 12 and 15. Furthermore, silver catalysis allowed access to be gained to 2-alkoxypyridine and 2-alkoxyisoquinoline derivatives starting from readily available imidate precursors.

Structure of a reactive gold carbenoid.

A formal gold-for-chromium transmetalation allowed the gold carbenoid species [Cy3 PAuCAr2 ]NTf2 (11) (Ar=pMeOC6 H4 -) to be obtained in crystalline form. The structure in the solid state suggests that there is only little back donation of electron density from gold to the carbene center of 11 and hence very modest AuC double-bond character; rather, it is the organic ligand framework that is responsible for stabilizing this species by resonance delocalization of the accumulated positive charge. Because 11 is capable of cyclopropanating p-methoxystyrene even at low temperature, the discussion of its structure is deemed relevant for a better understanding of the mechanisms of π-acid catalysis in general.

Gold carbenoids: lessons learnt from a transmetalation approach.

Carbophilic catalysts that are based on Au(I) allow a host of different nucleophiles to be added across various π systems. Although many of these reactions are thought to proceed via gold carbenoids, the challenge to observe and characterize these putative intermediates has basically been unmet. The current mechanistic interpretation therefore largely relies on indirect evidence and computational data, some of which are subject to debate. In an attempt to fill this gap, we pursued a potential route to gold carbenoids by formal transmetalation of chromium or tungsten Fischer carbene complexes with [LAu](+). Whereas this transformation proceeds with exceptional ease as long as a stabilizing heteroelement is present on the carbene center, it stops half-way in its absence. Rather unusual bimetallic arrays are formed, which allow the charge density to delocalize over several positions. The obvious difficulty of releasing an "unstabilized" gold carbenoid has potential mechanistic implications for the understanding of π-acid catalysis in general.

Optimized synthesis, structural investigations, ligand tuning and synthetic evaluation of silyloxy-based alkyne metathesis catalysts.

Nitride- and alkylidyne complexes of molybdenum endowed with triarylsilanolate ligands are excellent (pre)catalysts for alkyne-metathesis reactions of all sorts, since they combine high activity with an outstanding tolerance toward polar and/or sensitive functional groups. Structural and reactivity data suggest that this promising application profile results from a favorable match between the characteristics of the high-valent molybdenum center and the electronic and steric features of the chosen Ar(3)SiO groups. This interplay ensures a well-balanced level of Lewis acidity at the central atom, which is critical for high activity. Moreover, the bulky silanolates, while disfavoring bimolecular decomposition of the operative alkylidyne unit, do not obstruct substrate binding. In addition, Ar(3)SiO groups have the advantage that they are more stable within the coordination sphere of a high-valent molybdenum center than tert-alkoxides, which commonly served as ancillary ligands in previous generations of alkyne metathesis catalysts. From a practical point of view it is important to note that complexes of the general type [(Ar(3)SiO)(3)Mo≡X] (X = N, CR; R = aryl, alkyl, Ar = aryl) can be rendered air-stable with the aid of 1,10-phenanthroline, 2,2'-bipyridine or derivatives thereof. Although the resulting adducts are themselves catalytically inert, treatment with Lewis acidic additives such as ZnCl(2) or MnCl(2) removes the stabilizing N-donor ligand and gently releases the catalytically active template into the solution. This procedure gives excellent results in alkyne metathesis starting from air-stable and hence user-friendly precursor complexes. The thermal and hydrolytic stability of representative molybdenum alkylidyne and -nitride complexes of this series was investigated and the structure of several decomposition products elucidated.

Introduction of a new model for time-continuous and non-contact investigations of in-vitro thrombolysis under physiological flow conditions.

BACKGROUND: Thrombolysis is a dynamic and time-dependent process influenced by the haemodynamic conditions. Currently there is no model that allows for time-continuous, non-contact measurements under physiological flow conditions. The aim of this work was to introduce such a model. METHODS: The model is based on a computer-controlled pump providing variable constant or pulsatile flows in a tube system filled with blood substitute. Clots can be fixed in a custom-built clot carrier within the tube system. The pressure decline at the clot carrier is measured as a novel way to measure lysis of the clot. With different experiments the hydrodynamic properties and reliability of the model were analyzed. Finally, the lysis rate of clots generated from human platelet rich plasma (PRP) was measured during a one hour combined application of diagnostic ultrasound (2 MHz, 0.179 W/cm2) and a thrombolytic agent (rt-PA) as it is commonly used for clinical sonothrombolysis treatments. RESULTS: All hydrodynamic parameters can be adjusted and measured with high accuracy. First experiments with sonothrombolysis demonstrated the feasibility of the model despite low lysis rates. CONCLUSIONS: The model allows to adjust accurately all hydrodynamic parameters affecting thrombolysis under physiological flow conditions and for non-contact, time-continuous measurements. Low lysis rates of first sonothrombolysis experiments are primarily attributable to the high stability of the used PRP-clots.

Life-long increase of substantia nigra hyperechogenicity in transcranial sonography.

Transcranial ultrasound of the substantia nigra (SN) shows a distinct hyperechogenicity in the majority of patients with Parkinson's disease. Recent studies indicate a larger area of hyperechogenicity in elderly healthy adult subjects. The present study aimed to determine the size of the SN hyperechogenicity and of the mesencephalic brainstem in children and adults without evidence of movement disorders. The areas of echogenicity in the substantia nigra (aSN) and the area of the ipsilateral midbrain (aMid) were assessed in 121 healthy infants and children as well as in 64 healthy adults. Furthermore, the ratio of aSN and aMid was calculated (S/M ratio). We found a positive correlation between age and aSN and between age and the S/M ratio. The values for aSN and S/M ratio were smaller in infants and children compared to healthy adults (aSNmax 0.06+/-0.05 cm2 vs. 0.13+/-0.08 cm2). The aSN and S/M ratio grew with increasing age in an almost linear progression. The increase of SN hyperechogenicity over time suggests that the biological process underlying this ultrasound finding may be more dynamic and possibly progressive than previously thought.

Cranial pachymeningitis: a rare neurological syndrome with heterogeneous aetiology.

Cranial pachymeningitis is a poorly understood syndrome, defined by leptomeningeal thickening and typical gadolinium enhanced MRI. The heterogeneous clinical and aetiological features of five patients with both focal and diffuse pachymeningitis are presented. The initial symptoms included headache (n=3), sensory Jackson seizures (n=1), hemiparesis (n=1), episodes of short lasting hemiataxia (n=1), hemihypaesthesia (n=1), aphasia (n=1) and confusion (n=2). MRI scans revealed focal (n=3) or diffuse (n=2) leptomeningeal gadolinium enhancement and cortical swelling (n=4). In addition, one case presented with a subarachnoid and a second with an intracerebral haemorraghe. CSF findings were variable and showed clear lymphomonocytic pleocytosis in 3/5 cases. Infectious diseases were extensively excluded in all cases. Leptomeningeal biopsies of two cases revealed perivascular inflammation, indicating central nervous system vasculitis. In the cases presented, pachymeningitis was caused by primary central nervous system vasculitis (n=2) and rheumatoid arthritis (n=2). In one case, the cause remained unclear.

Sonographic evaluation of hemorrhagic transformation and arterial recanalization in acute hemispheric ischemic stroke.

BACKGROUND AND PURPOSE: We conducted this prospective study to evaluate the time course of hemorrhagic transformation (HT) and arterial recanalization in the early phase of ischemic stroke using transcranial sonography (TCS). METHODS: Fifty-five patients with acute ischemic hemispheric stroke <32 hours after symptom onset were studied. A 2-MHz sector probe was used to evaluate brain tissue by TCS and basal cerebral arteries by transcranial color-coded sonography. Follow-up investigations were performed up to 6 days. Lesion size and localization were determined by cranial computed tomography. RESULTS: Of 20 patients with HT, 18 displayed by computed tomography could be identified by TCS. In 1 patient, TCS provided a wrong positive result, and in another 2 patients with small cortical HT, a wrong negative result was provided (sensitivity 90.0%, specificity 97.4%). HT was detected in the first 60 hours after symptom onset in 62.5% of patients treated with tissue plasminogen activator in comparison to 33.3% without thrombolysis. Recanalization of middle cerebral artery occurred earlier in tissue plasminogen activator-treated patients compared to those without tissue plasminogen activator treatment (in the first 60 hours after symptom onset: 78.5% vs 50.0%, respectively; P=0.34). There was a significant time difference between middle cerebral artery recanalization and HT occurrence (n=13, median time interval: 20 vs 60 hours; P=0.035). CONCLUSIONS: Transcranial ultrasound is a useful bedside method to depict and closely monitor HT in patients with acute hemispheric stroke. The strong influence of tissue plasminogen activator treatment on HT could be demonstrated. HT development is dependent on the time of artery recanalization.

Ultrasound contrast agents in ischemic stroke.

The general indication for the use of ultrasound contrast agents in neurosonologic applications is an insufficient signal-to-noise ratio when investigating the cerebral macro- and microcirculation. Clinical problems that are often encountered in native sonography are 'no flow, slow flow and low flow' phenomena. In these cases, ultrasound contrast agents are used to differentiate between vessel occlusion and insufficient insonation conditions, as well as for the detection of very slow blood flow velocities and low flow volumes. Echo-contrast agents significantly increase the success rate of transcranial color duplex examinations of patients with acute cerebrovascular disease. Ultrasound contrast imaging also allows assessment of the cerebral microcirculation. There are a number of techniques available for performing perfusion studies. These generally utilize high mechanical index imaging, since until recently lower acoustic outputs were unable to detect microbubbles in the brain. New-generation microbubbles in combination with very sensitive contrast-specific ultrasound techniques now enable real-time visualization of stroke. Moreover, destruction sequences with assessment of microbubble replenishment using real-time, low mechanical index imaging are now available. This article reviews of state-of-the-art contrast-specific imaging techniques for ultrasound evaluation of acute stroke patients.

Bedside screening for executive dysfunction in patients with subcortical ischemic vascular disease.

OBJECTIVE: We investigated several executive bedside tests for their effectiveness in the routine clinical diagnostics of dysexecutive syndrome in subcortical ischemic vascular disease (SIVD). METHODS: Five executive tests, CLOX, the Tower of London (ToL), a cognitive estimation test (CET), a verbal fluency test, and the Five-Point Test, were examined in 17 patients with marked cerebral microangiopathy in cranial MRI and clinical symptoms of SIVD. The test accuracy for discriminating the patients from 17 healthy comparison subjects closely matched for age, gender and level of education was determined. RESULTS: Aside from the CET we found a significant lower performance of the patients with SIVD in four of the five used executive tests. In receiver operating characteristic (ROC) analyses the accuracy of CLOX 1 showed excellent results for distinguishing between patients and comparison subjects (area under the curve (AUC) 0.901), while the ToL (AUC up to 0.845) and the productivity in the phonemic verbal fluency test (AUC 0.829) achieved a good accuracy. Differently the accuracy of the figural fluency was only poor to fair (AUC 0.706). However, the Youden Indices of the significant executive variables showed a wide range from 0.25 to 0.82. CONCLUSIONS: Based on our data we consider CLOX, the ToL and the verbal fluency test promising executive bedside test concepts for diagnosing the dysexecutive syndrome in SIVD in clinical routine. Particularly for CLOX and the ToL a further psychometric evaluation is required.

Detecting stripe artifacts in ultrasound images.

Brain perfusion diseases such as acute ischemic stroke are detectable through computed tomography (CT)-/magnetic resonance imaging (MRI)-based methods. An alternative approach makes use of ultrasound imaging. In this low-cost bedside method, noise and artifacts degrade the imaging process. Especially stripe artifacts show a similar signal behavior compared to acute stroke or brain perfusion diseases. This document describes how stripe artifacts can be detected and eliminated in ultrasound images obtained through harmonic imaging (HI). On the basis of this new method, both proper identification of areas with critically reduced brain tissue perfusion and classification between brain perfusion defects and ultrasound stripe artifacts are made possible.

Elementary steps of gold catalysis: NMR spectroscopy reveals the highly cationic character of a "gold carbenoid".

What are you? Even though the metal-induced ring opening of 3,3-disubstituted cyclopropenes is known to serve as a genuine carbene generator, the use of Au(I) in this reaction leads to a reactive intermediate with highly cationic character. This result has important implications for gold catalysis in general, which in the past has been commonly attributed to the intervention of gold carbenes.

Sonothrombolysis with transcranial color-coded sonography and recombinant tissue-type plasminogen activator in acute middle cerebral artery main stem occlusion: results from a randomized study.

BACKGROUND AND PURPOSE: Sonothrombolysis is a new treatment approach in acute ischemic stroke. The results of a monocenter, randomized clinical study are presented. METHODS: Subjects with acute middle cerebral artery main stem occlusion were randomized into a target group receiving 1-hour transcranial continuous insonation using a 1.8-MHz Doppler ultrasound (US) probe or a control group. All underwent standard thrombolysis with intravenous recombinant tissue-type plasminogen activator. RESULTS: Thirty-seven subjects were included; 19 subjects were treated in the target (US) group and 18 in the control (no-US) group, all with no residual flow in the middle cerebral artery main stem occlusion (Thrombolysis in Brain Ischemia recanalization grade 0). Compared with the no-US group, the US group showed greater improvement in National Institutes of Health Stroke Scale values at days 1 and 4 and a higher median Thrombolysis in Brain Ischemia grade 1 hour after recombinant tissue-type plasminogen activator initiation. Recanalization (complete or partial) after 1 hour occurred in 57.9% of the US group and 22.2% of the no-US group (P=0.045). After 90 days, 4 subjects from the US group had a modified Rankin Score or=95 (none from the no US group; P=0.106 and P=0.003, respectively). Three subjects from the US group (15.8%) developed a symptomatic intracranial hemorrhage as did one (5.6%) in the no-US group (P=0.60). CONCLUSIONS: This small randomized study indicates a beneficial impact of transcranial ultrasound on recanalization and short-term outcome in subjects with middle cerebral artery main stem occlusion and recombinant tissue-type plasminogen activator treatment.