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Diedler J.,University of Heidelberg | Ahmed N.,Karolinska University Hospital | Glahn J.,Johannes Wesling Klinikum | Grond M.,Kreisklinikum Siegen | And 4 more authors.
Stroke | Year: 2011

Background And Purpose- Intravenous alteplase for acute ischemic stroke has a maximum dose limit of 90 mg. Consequently, patients >100 kg body weight receive a lower per-kilogram dose compared with those ≤100 kg. We investigated if the lower per-kilogram dose is associated with poor early neurological improvement and worse outcome after thrombolysis. Methods- Of 27 910 patients registered in Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Register (SITS-ISTR; 2002 to 2009), 1190 (4.3%) weighed >100 kg. Major neurological improvement was used to estimate recanalization (National Institutes of Health Stroke Scale improvement 8 points or score of 0 at 24 hours). Outcome measures included symptomatic intracerebral hemorrhage (National Institutes of Health Stroke Scale deterioration 4 points within 24 hours and Type 2 parenchymal hemorrhage), functional independence (modified Rankin Scale 0 to 2), and mortality at 3 months. Results- Patients >100 kg received a lower per-kilogram alteplase dose (0.82 versus 0.90, P<0.001), were younger (62 versus 70 years, P<0.001), had a lower baseline National Institutes of Health Stroke Scale (10 versus 12, P<0.001), but more frequently had cardiovascular risk factors. Major neurological improvement at 24 hours occurred in 27.7% in both groups. Symptomatic intracerebral hemorrhage occurred in 2.6% versus 1.7% (P=0.03) in >100 kg versus ≤100 kg. Functional independence was 59.7% versus 53.6% (P<0.001) and mortality was 14.4% versus 15.1% (P=0.54). After adjustment for baseline characteristics, there was no significant difference for major neurological improvement or functional independence between >100 kg and ≤100 kg, but >100-kg patients had a higher odds ratio for symptomatic intracerebral hemorrhage (OR, 1.6; 95% CI, 1.06 to 2.41; P=0.02) and mortality (OR, 1.37; 95% CI, 1.08 to 1.74; P=0.01). Conclusions- Our results support the current upper dose limit. There was a higher incidence of symptomatic intracerebral hemorrhage in patients >100 kg despite the lower per-kilogram recombinant tissue plasminogen activator dose. Major neurological improvement and functional independence were similar. © 2011 American Heart Association, Inc.


PubMed | Charité - Medical University of Berlin, HELIOS Dr. Horst Schmidt Kliniken Wiesbaden, Heinrich Heine University Düsseldorf, University of Duisburg - Essen and 22 more.
Type: Journal Article | Journal: Zeitschrift fur Rheumatologie | Year: 2016

In a joint initiative by the boards of the German Society for Rheumatology (DGRh) and the Association of Rheumatology Clinics (VRA) the European standards of care for rheumatoid arthritis, recently suggested by the European Musculoskeletal Conditions Surveillance and Information Network (eumusc.net) and supported by the European League Against Rheumatism (EULAR), were translated and annotated. The recommendations include aspects of the management of the disease, actual medical care, and access to information - this includes all types of support people with RA need, and, last but not least communication of the necessary knowledge. Furthermore, health care structures such as the availability of medical staff with relevant expertise are also important.


Whittaker S.,King's College London | Ortiz P.,Hospital Universitario 12 Of Octubre | Dummer R.,University of Zürich | Ranki A.,University of Helsinki | And 6 more authors.
British Journal of Dermatology | Year: 2012

Background Psoralen plus ultraviolet A (PUVA) is the standard treatment for early stages of mycosis fungoides. There have been no adequate randomized controlled trials with sufficient power comparing this modality with other therapies. Objective To assess disease response and to compare the response rates of patients treated with PUVA alone or PUVA and bexarotene. Methods EORTC 21011 (NCT 00056056) was a randomized phase III study comparing combined bexarotene (Targretin®) and PUVA vs. PUVA alone in patients with stage IB and IIA mycosis fungoides (MF). The primary endpoint was the overall response rate [complete clinical response (CCR) plus partial response (PR)]. Results The study was prematurely closed due to low accrual after 93 of 145 required patients (65%) were randomized. Of the 93 randomized patients, 87 started treatment, 41 received PUVA and 46 received PUVA + bexarotene. Total UVA doses received were 107 J cm-2 (range 1·4-489·9) in the PUVA arm vs. 101·7 J cm-2 (0·2-529·9) in the combination arm. The safety profile was acceptable with few grade 3-4 toxicities observed in either arm. More drop-outs due to toxicity were observed in the combination arm compared with the PUVA-alone arm. The best overall response (CCR + PR) rate was 71% for PUVA alone and 77% for the combination arm (P = 0·57). The median duration of response was 9·7 months for PUVA vs. 5·8 months for the combination arm (P = 0·33). CCR was seen in 25 patients of whom 10 received PUVA alone (CCR 22%) and 15 received combination therapy (CCR 31%) (P = 0·45). CCR was sustained in 25% of patients regardless of therapy. There was a trend towards fewer PUVA sessions needed to achieve CCR in the combination arm (median 22) compared with the PUVA arm (median 27·5) (P = 0·11). Similarly, a trend towards lower UVA dose required to achieve CCR in the combination arm (median 55·8 J cm-2) compared with the PUVA arm alone (median 117·5 J cm -2) (P = 0·5) was observed. Conclusions No significant difference in response rate or response duration was observed in this study. However, there was a trend towards fewer PUVA sessions and lower UVA dose required to achieve CCR in the combination arm (PUVA + bexarotene) but this did not achieve statistical significance due to insufficient power. See also the Commentary by Ahmed and Piguet © 2012 British Association of Dermatologists.


Schellinger P.D.,Johannes Wesling Klinikum | Kohrmann M.,Friedrich - Alexander - University, Erlangen - Nuremberg | Liu S.,University of California at San Francisco | Dillon W.P.,University of California at San Francisco | And 3 more authors.
Stroke | Year: 2013

Background and Purpose-We hypothesized that a favorable vascular profile (FVP) defined as anatomic intactness of the Circle of Willis combined with a stable cerebral perfusion pressure (mean arterial blood pressure>65 mm Hg) is a prerequisite for collateral recruitment and maintenance and may improve outcome. We performed post hoc analyses of a subset of the Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke (SENTIS) trial data set to identify whether FVP is associated with independent outcome. Methods-SENTIS was a randomized, controlled device trial comparing hemodynamic augmentation with the NeuroFlo device to best medical treatment. We identified all patients from the primary dataset (n=515 patients) with available intracranial vascular imaging at baseline. Vascular imaging data were read blind to clinical and treatment data. We performed univariate and multivariate analyses to identify predictors of independent outcome (modified Rankin Scale 0-2) at 90 days. Results-A total of 192/515 SENTIS subjects had available baseline vascular imaging (91 treated/101 controls). Baseline characteristics did not differ between groups. Overall, FVP was seen in 89.6% of patients and predicted independent outcome in univariate (odds ratio, 7.46; 95% confidence interval, 1.68-33.18; P=0.0082) and multiple logistic regression analyses (odds ratio, 10.22; 95% confidence interval, 1.78-58.57; P=0.0091). Aside from FVP, only baseline National Institutes of Health Stroke Scales (NIHSS; odds ratio, 0.74; 95% confidence interval, 0.67-0.82, P<0.0001) entered the predictive model. There was no interaction with randomization to treatment or control. Conclusions-FVP and baseline NIHSS independently predicted outcome in this subset of the SENTIS population. FVP is a novel parameter to predict outcome of acute stroke patients and further studies will establish its potential role for selection of optimal candidates for hemodynamic augmentation. © 2013 American Heart Association, Inc.


Ahmed N.,Karolinska University Hospital | Davalos A.,Autonomous University of Barcelona | Eriksson N.,Uppsala University | Ford G.A.,Northumbria University | And 7 more authors.
Archives of Neurology | Year: 2010

Objective: To determine the association between admission blood glucose and outcome in ischemic stroke patients treated with thrombolysis. Design: A prospective, open, multinational, observational study. Setting: An ongoing Internet-based, academic-driven, interactive thrombolysis register. Patients: Between 2002 and 2007, 16 049 patients were recorded in the SITS-ISTR. Main Outcome Measure: Blood glucose was recorded at admission. Blood glucose was divided into the following categories: less than 80, 80-120 (reference range), 121-140, 141-160, 161-180, 181-200, and greater than 200 mg/dL. Outcomes were mortality and independence (modified Rankin Scale score of 0-2) at 3 months and symptomatic intracerebral hemorrhage (SICH) (National Institutes of Health Stroke Scale deterioration ≥4 points within 24 hours and type 2 parenchymal hemorrhage). Results: In multivariable analysis, blood glucose as a continuous variable was independently associated with a higher mortality (P < .001), lower independence (P < .001), and an increased risk of SICH (P = .005). Blood glucose greater than 120 mg/dL as a categorical variable was associated with a significantly higher odds for mortality (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.07-1.44; P=.004) and a lower odds for independence (OR, 0.58; 95% CI, 0.48-0.70; P < .001), and blood glucose from 181 to 200 mg/dL was associated with an increased risk of SICH (OR, 2.86; 95% CI, 1.69-4.83; P < .001) compared with the reference level. The trends of associations between blood glucose and outcomes were similar in patients with diabetes (17%) or without such history, except for mortality (P = .23) and SICH (P = .06) in which the association was not statistically significant in patients with diabetes. Conclusions: Admission hyperglycemia was an independent predictor for poor outcome after stroke/thrombolysis, though SICH rates did not increase significantly until reaching 180 mg/dL. These results suggest that tight control of blood glucose may be indicated in the hyperacute phase following thrombolysis. Randomized trial data are needed. ©2010 American Medical Association. All rights reserved.


Rocco A.,University of Heidelberg | Rocco A.,Charité - Medical University of Berlin | Heuschmann P.U.,University of Würzburg | Schellinger P.D.,Johannes Wesling Klinikum | And 9 more authors.
Stroke | Year: 2013

BACKGROUND AND PURPOSE-: Symptomatic intracerebral hemorrhage (sICH) is the most feared acute complication after intravenous thrombolysis. The aim of this study was to determine the predictive value of parameters of glycosylated hemoglobin A1 (HbA1c) on sICH. METHODS-: In a retrospective single center series, 1112 consecutive patients treated with thrombolysis were studied. Baseline blood glucose was obtained at admission. HbA1c was determined within hospital stay. A second head computed tomography was obtained after 24 hours or when neurological worsening occurred. Modified Rankin Scale was used to assess outcome at 90 days. RESULTS-: A total of 222 patients (19.9%) had any hemorrhage; 43 of those had sICH (3.9%) per Safe Implementation of Treatments in Stroke definition and 95 (8.5%) per National Institute of Neurological Disorders and Stroke definition; 33.2% of patients had a dependent outcome (modified Rankin Scale score 3-5). In univariate analysis history of diabetes mellitus, HbA1c, blood glucose, and National Institute of Health Stroke Scale score on admission were associated with any hemorrhage and sICH. In multivariate analysis National Institute of Health Stroke Scale score, a history of diabetes mellitus, and HbA1c were predictors of sICH per National Institute of Neurological Disorders and Stroke, and only HbA1c when Safe Implementation of Treatments in Stroke criteria were used. CONCLUSIONS-: In our study, HbA1c turns out to be an important predictor of sICH after thrombolysis for acute stroke. These results suggest that hemorrhage after thrombolysis may be a consequence of long-term vascular injury rather than of acute hyperglycemia, and that HbA1c may be a better predictor than acute blood glucose or a history of diabetes mellitus. © 2013 American Heart Association, Inc.


Doeppner T.R.,University of Duisburg - Essen | Kaltwasser B.,University of Duisburg - Essen | Teli M.K.,University of Duisburg - Essen | Teli M.K.,National Institute of Technology Calicut | And 4 more authors.
Cell Death and Disease | Year: 2014

Intravenous transplantation of neural progenitor cells (NPCs) induces functional recovery after stroke, albeit grafted cells are not integrated into residing neural networks. However, a systematic analysis of intravenous NPC delivery at acute and post-acute time points and their long-term consequences does not exist. Male C57BL6 mice were exposed to cerebral ischemia, and NPCs were intravenously grafted on day 0, on day 1 or on day 28. Animals were allowed to survive for up to 84 days. Mice and tissues were used for immunohistochemical analysis, flow cytometry, ELISA and behavioral tests. Density of grafted NPCs within the ischemic hemisphere was increased when cells were transplanted on day 28 as compared with transplantation on days 0 or 1. Likewise, transplantation on day 28 yielded enhanced neuronal differentiation rates of grafted cells. Post-ischemic brain injury, however, was only reduced when NPCs were grafted at acute time points. On the contrary, reduced post-ischemic functional deficits due to NPC delivery were independent of transplantation paradigms. NPC-induced neuroprotection after acute cell delivery was due to stabilization of the blood-brain barrier (BBB), reduction in microglial activation and modulation of both peripheral and central immune responses. On the other hand, post-acute NPC transplantation stimulated post-ischemic regeneration via enhanced angioneurogenesis and increased axonal plasticity. Acute NPC delivery yields long-term neuroprotection via enhanced BBB integrity and modulation of post-ischemic immune responses, whereas post-acute NPC delivery increases post-ischemic angioneurogenesis and axonal plasticity. Post-ischemic functional recovery, however, is independent of NPC delivery timing, which offers a broad therapeutic time window for stroke treatment. © 2014 Macmillan Publishers Limited All rights reserved.


Lubbers T.,Ludmillenstift Krankenhaus | Abuamona R.,Ludmillenstift Krankenhaus | Elsharkawy A.E.,Johannes Wesling Klinikum
Acta Neurochirurgica | Year: 2012

Background: Microsurgery of foraminal and extraforaminal disc herniation at the L5-S1 level remains a challenge because of the limited access by a high iliac crest, the sacral ala, large transverse processes of L5 and hidden disc fragments lateral to the zygapophyseal joint. Our aim was to present the outcome of percutaneous endoscopic lumbar discectomy (PELD) of these lateral and far lateral disc herniations at the L5-S1 level using the newly described foraminal retreat technique in a group of patients with similar preoperative diagnostic studies. Methods: A total of 22 patients, 13 males and 9 females, with foraminal and extraforaminal lumbar disc herniation at the L5-S1 level were treated by applying the PELD between September 2004 and April 2010. The clinical findings and MRI were the main diagnostic methods. Preoperative evaluation was performed with clinical examinations, the Visual Analog Pain Scale (VAS) and Oswestry Low Back Disability Index (ODI). Findings: According to the Macnab criteria, overall excellent or good outcomes were obtained in 18 patients (81.8 %), fair outcomes in 3 patients (13.6 %) and a poor outcome in 1 patient (4.5 %) at the last follow-up. The mean ODI was 67.3 ±19.4 preoperatively and 26.7 ±23.4 postoperatively. Preoperative VAS was 88.6±7.6 and 28.6±22.8 at 2 days, 40.5±22.8 at 3 weeks, 34.3±25.1 at 6-months and 32 at the last follow-up. At follow-up, two patients (9.1 %) had recurrent disc herniations that were corrected with open surgery. At the time of surgery, 16 patients held jobs. Fifteen (15) patients (93.8 %) returned to their original jobs postoperatively; one patient could not return to his original job postoperatively because of a comorbidity. Conclusions: Percutaneous endoscopic discectomy using the foraminal retreat technique is an effective treatment method for patients with foraminal and extraforaminal disc herniations at the L5-S1 level on appropriately selected patients. © Springer-Verlag 2012.


Knappe U.J.,Johannes Wesling Klinikum | Fink T.,Institute of Pathology and Cytology | Fisseler-Eckhoff A.,Institute of Pathology and Cytology | Schoenmayr R.,Dr. Horst Schmidt Klinik
Acta Neurochirurgica | Year: 2010

Purpose: To describe the pattern of expression of extracellular matrix (ECM) proteins in perisellar connective tissue. Methods: Dural and perisellar specimens from ten individuals were investigated immunohistochemically for collagens I to IV, tenascin, fibronectin, elastin, laminin, and vitronectin. Findings: Collagen I and III and fibronectin were strongly expressed and collagen IV, tenascin, and vitronectin were moderately expressed in the boundaries of the sella and around the CS. In six of nine specimens from the anterior boundary of the sella, and in 11 of 19 samples from the lateral boundary of the sella (medial wall of CS), two different layers could be detected by the expression of different ECM proteins. None of the antigens generally allowed differentiation between two layers of the pituitary envelope. Conclusions: The pituitary boundary may consist of a single or a double layer, infrequently differentiated from each other by the expression of different ECM proteins. © 2009 Springer-Verlag.

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