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Introduction: Efforts are increasingly aiming to develop in vitro models that can provide effective alternatives to in vivo experiments. The main aim of this study was the establishment of an in vitro model of the nonkeratinized mucous membrane that can be used as a standardized tool to evaluate biological and therapeutic effects of pharmaceuticals for mucosal wound healing., Methods: We established a full-thickness in vitro model of the nonkeratinized mucous membrane. While histological examination was performed to assess morphological characteristics, we utilized gene expression profiling using microarray and qRT-PCR analyses to identify molecular effects of treatment with a dexpanthenol-containing ointment after laser wounding., Results: Performing histological and immunofluorescence analyses we proved that our model mimics the two distinctive layers of the mucous membrane - the stratified squamous epithelium and the lamina propria. We used this model to investigate molecular effects of a dexpanthenol-containing ointment that is commonly used for the wound treatment of mucous membranes. For that purpose, our model exhibits a unique feature in that dexpanthenol and proliferation-enhancing additives that may interfere with our studies are not required for the maintenance of the model culture. After setting standardized lesions with a nonsequential fractional ultrapulsed CO2 laser, topical treatment with the dexpanthenol-containing ointment enhanced wound closure in the model compared to placebo and untreated controls. Furthermore, microarray analysis revealed that the treatment of the laser-wounded model with the dexpanthenol-containing ointment evoked an upregulated expression of various genes related to accelerated wound healing., Conclusion: Overall, we verified that this novel mucous membrane model can be utilized in future to monitor ex vivo effects of various topical therapies on mucosa morphology, physiology, and gene expression. Our findings confirm the potential of the model as an in vitro tool for the replacement of pharmacological in vivo studies regarding mucosal wound healing., (© 2019 S. Karger AG, Basel.)

Due to the recommendations in the urological guidelines to perform nephron-sparing surgery in patients with organ-confined renal cell carcinoma (RCC), the customary therapy regimen changed, but it is not well studied yet whether partial nephrectomy (PN) especially in the elderly is beneficial. From 2000 to 2015, 3,592 patients from 7 clinics undergoing surgery in RCC were identified; 2,323 had T1 tumours. We retrospectively compared the overall survival benefit of patients with T1 RCC who underwent either PN or radical nephrectomy (RN) and studied effects of age and gender., Results: In T1 RCC, PN was beneficial in male patients (p = 0.0006) independent of age, especially in those men ≤75 years of age (p = 0.0005); but PN was not beneficial for female patients (p = 0.0629) regardless of age and male patients older than 75 years (p = 0.736). The OS of female patients after RN and male patients after PN is the same, regardless of age. A life expectancy of more than 45 months at least is necessary to experience an overall survival benefit after PN., Conclusions: There should be harder proven indications for PN in female patients and especially in all patients older than 75 years, particularly with regard to perioperative risk factors., (© 2018 S. Karger AG, Basel.)

Background: The first specific antidote for non-vitamin K antagonist oral anticoagulants (NOAC) has recently been approved. NOAC antidotes will allow specific treatment for 2 hitherto problematic patient groups: patients with oral anticoagulant therapy (OAT)-associated intracerebral hemorrhage (ICH) and maybe also thrombolysis candidates presenting on oral anticoagulation (OAT). We aimed to estimate the frequency of these events and hence the quantitative demand of antidote doses on a stroke unit., Methods: We extracted data of patients with acute ischemic stroke and ICH (<24 h after symptom onset) in the years 2012-2015 from a state-wide prospective stroke inpatient registry. We selected 8 stroke units and determined the mode of OAT upon admission in 2012-2013. In 2015, the mode of OAT became a mandatory item of the inpatient registry. From the number of anticoagulated patients and the NOAC share, we estimated the current and future demand for NOAC antidote doses on stroke units., Results: Eighteen percent of ICH patients within 6 h of symptom onset or an unknown symptom onset were on OAT. Given a NOAC share at admission of 40%, about 7% of all ICH patients may qualify for NOAC reversal therapy. Thirteen percent of ischemic stroke patients admitted within 4 h presented on anticoagulation. Given the availability of an appropriate antidote, a NOAC share of 50% could lead to a 6.1% increase in thrombolysis rate., Conclusions: Stroke units serving populations with a comparable demographic structure should prepare to treat up to 1% of all acute ischemic stroke patients and 7% of all acute ICH patients with NOAC antidotes. These numbers may increase with the mounting prevalence of atrial fibrillation and an increasing use of NOAC., (© 2016 S. Karger AG, Basel.)

Background: Prothrombin complex concentrates (PCCs) are frequently used to reverse the effect of vitamin K antagonists (VKAs) in patients with non-traumatic intracerebral hemorrhage (ICH). However, information on the rate of thromboembolic events (TEs) and allergic events after PCC therapy in VKA-ICH patients is limited., Methods: Consecutive VKA-ICH patients treated with PCC at our institution between December 2004 and June 2014 were included into this retrospective observational study. We recorded international normalized ratio (INR) values before and after PCC treatment, baseline clinical characteristics including the premorbid modified Rankin Scale (pmRS) score, TE and allergic event that occurred during the hospital stay. All events were classified by 3 reviewers as being 'related', 'probably related', 'possibly related', 'unlikely related' or 'not related' to treatment with PCC. To identify factors associated with TEs, log-rank analyses were applied., Results: Two hundred and five patients were included. Median INR was 2.8 (interquartile range (IQR) 2.2-3.8) before and 1.3 (IQR 1.2-1.4) after PCC treatment and a median of 1,500 IU PCC (IQR 1,000-2,500) was administered. Nineteen TEs were observed (9.3%); none were classified 'related' but 9 were classified as 'possibly' or 'probably related' to PCC infusion (4.4%). One allergic reaction (0.5%), 'unlikely related' to PCC, was observed. In the whole cohort, PCC doses >2,000-3,000 IU, ICH volumes >40 ml, National Institute of Health Stroke Scale values >10 and a pmRS >2 were associated with the development of TEs (p = 0.031, p = 0.034, p = 0.050 and p = 0.036, respectively)., Conclusions: Overall, INR reversal with PCC appears safe. Though no clear relationship between higher PCC dosing and TEs was observed, PCC doses between >2,000 and 3,000 IU and higher morbidity at ICH onset were associated with TEs. Hence, individual titration of PCC to avoid exposure to unnecessarily high doses using point-of-care devices should be prospectively explored., (© 2016 S. Karger AG, Basel.)

Outcome of intracerebral hemorrhage (ICH) is still poor and siginificantly influenced by complications during the acute phase, so optimized neurocritical care is crucial. Vital parameters, neurological status and laboratory values of ICH-patient should be monitored very closely with special attention on blood pressure and intracranial pressure. Systolic blood pressure should be kept <140 mm Hg and intracranial pressure <20 mm Hg. Administration of hemostatic agents in spontaneous ICH without intake of anticoagulants is actually not recommended out of clinical trials. Neurosurgical treatment of ICH is still an individual decision. Patients with a higher level of consciousness may profit from an early operation., (© 2016 S. Karger AG, Basel.)

Background: Different aspects of acute stroke management and strategies for stroke prevention derive from two viewpoints: specific traditional and historical backgrounds and evidence-based medicine from modern randomized controlled trials (RCTs), meta-analysis and authorized clinical practice guidelines (GLs). Regarding stroke, GLs have been published by national and international organizations in different languages, most frequently in English. Cerebrovascular Diseases published the European GLs for the management of ischemic stroke and transient ischemic attacks in 2003, with an update in 2008. At about the same time (in 2004), the first Japanese GLs for the management of stroke appeared in Japanese. The first English version of the updated Japanese GLs was published only in 2011 and included differently approved drugs and drug dosages as compared with other American or European countries., Methods: Since 2011, the authors have met repeatedly and have compared the latest versions of published European and Japanese GLs for ischemic and hemorrhagic strokes. Many aspects have only been addressed in one but left out in the other GLs, which consequently founded the basis for the comparison. Classification of evidence levels and recommendation grades defined by the individual committees differed between both original GLs., Results: Aspects of major importance were surprisingly similar and hence did not need extensive interpretation. Other aspects of ischemic stroke management differed significantly, e.g. the dosage of recombinant tissue plasminogen activator approved in Japan is lower (0.6 mg/kg) than in Europe (0.9 mg/kg), which derived from different practices in cardiovascular treatment prior to the design of acute ischemic stroke RCTs. Furthermore, comedication with neuroprotective agents (edaravone), intravenous anticoagulants (argatroban) or antiplatelet agents within 1-2 days after stroke onset is recommended in Japan but not in Europe. For cardioembolic stroke prevention, a major difference consists in a higher international normalized ratio target (2.0-3.0) in younger subjects versus in those >70 years (1.6-2.6), without age restrictions in Europe., Conclusion: This brief survey - when compared with the lengthy original recommendations - provides a stimulating basis for an extended interest among Japanese and European stroke clinicians to learn from their individual experiences and to strengthen efforts for joint cooperation in treating and preventing stroke all around the globe., (Copyright © 2013 S. Karger AG, Basel.)

Background: Prognostic signs for the identification of patients with acute spontaneous intracerebral hemorrhage (SICH) prone to hematoma expansion are limited. Contrast extravasation (spot signs, SpS) on computed tomographic angiography (CTA) may be a promising method to predict hematoma expansion in acute SICH. However, prospective data on the predictive value of the SpS on hematoma expansion and clinical outcome are still limited. We aimed to investigate associations between the presence of SpS, hematoma expansion, and clinical outcome in acute SICH., Methods: A prospective observational study was performed between 08/2008 and 08/2011. Patients with SICH presenting within 6 h of symptom onset were included. Patients with secondary hematomas, purely intraventricular hematomas, incomplete CT evaluation, hematoma evacuation prior to follow-up brain imaging, and incomplete follow-up data and those who refused to give consent for data analysis were excluded. CT and CTA brain imaging were carried out in all patients at baseline. After 24 h, follow-up brain imaging was performed. Hematoma location, hematoma volume, and substantial hematoma expansion were documented. CTA images were evaluated by two investigators for the presence of SpS. In all positive SpS cases, images were additionally reviewed by a third rater to achieve consensus for interpretating contrast extravasation. Clinical outcome was measured by the modified Rankin Scale (mRS) at discharge and at 3 months., Results: In total, 101 patients [median age 73 years (interquartile range 60-79); male 61.4%] were included in the analysis. Median time from onset to CTA was 128 min (interquartile range 90-209 min); median initial National Institute of Health Stroke Scale score was 16 (8-21). SpS were detected in 27 patients (26.7%). Cohen's kappa for the presence of SpS was 0.606, indicating moderate agreement. SpS patients had significantly higher initial hematoma volumes than patients without SpS (36.0 vs. 14.39 ml, p = 0.005). Hematoma expansion was significantly more frequent in SpS patients (59.3 vs. 21.6%, p < 0.001) and associated with the presence of SpS in the univariate analysis (OR 5.273; 95% CI 2.047-13.584, p = 0.001) and in multivariable analysis adjusted for the initial hematoma volume (OR 4.678, 95% CI 1.781-12.288, p = 0.002). Sensitivity of SpS to predict hematoma expansion was 0.5, specificity was 0.84. The positive likelihood ratio for SpS to predict hematoma expansion was 3.136 (95% CI 1.649-5.967), the negative likelihood ratio was 0.595 (95% CI 0.414-0.854). No difference in 3-month clinical outcome was observed between patients with and without SpS (median mRS score 4 and 4, p = 0.457)., Conclusions: The clinical value of SpS needs to be further explored. Future studies should particularly focus on structured training procedures to identify SpS and measure the time needed to precisely assess the presence of SpS and on the prevalence of SpS in consecutive intracerebral hemorrhage populations., (Copyright © 2013 S. Karger AG, Basel.)

Background: Intracranial aneurysm with and without subarachnoid haemorrhage (SAH) is a relevant health problem: The overall incidence is about 9 per 100,000 with a wide range, in some countries up to 20 per 100,000. Mortality rate with conservative treatment within the first months is 50-60%. About one third of patients left with an untreated aneurysm will die from recurrent bleeding within 6 months after recovering from the first bleeding. The prognosis is further influenced by vasospasm, hydrocephalus, delayed ischaemic deficit and other complications. The aim of these guidelines is to provide comprehensive recommendations on the management of SAH with and without aneurysm as well as on unruptured intracranial aneurysm., Methods: We performed an extensive literature search from 1960 to 2011 using Medline and Embase. Members of the writing group met in person and by teleconferences to discuss recommendations. Search results were graded according to the criteria of the European Federation of Neurological Societies. Members of the Guidelines Committee of the European Stroke Organization reviewed the guidelines., Results: These guidelines provide evidence-based information on epidemiology, risk factors and prognosis of SAH and recommendations on diagnostic and therapeutic methods of both ruptured and unruptured intracranial aneurysms. Several risk factors of aneurysm growth and rupture have been identified. We provide recommendations on diagnostic work up, monitoring and general management (blood pressure, blood glucose, temperature, thromboprophylaxis, antiepileptic treatment, use of steroids). Specific therapeutic interventions consider timing of procedures, clipping and coiling. Complications such as hydrocephalus, vasospasm and delayed ischaemic deficit were covered. We also thought to add recommendations on SAH without aneurysm and on unruptured aneurysms., Conclusion: Ruptured intracranial aneurysm with a high rate of subsequent complications is a serious disease needing prompt treatment in centres having high quality of experience of treatment for these patients. These guidelines provide practical, evidence-based advice for the management of patients with intracranial aneurysm with or without rupture. Applying these measures can improve the prognosis of SAH., (Copyright © 2013 S. Karger AG, Basel.)

Background: Different aspects of acute stroke management and strategies for stroke prevention derive from two viewpoints: specific traditional and historical backgrounds and evidence-based medicine from modern randomized controlled trials (RCTs), meta-analysis and authorized clinical practice guidelines (GLs). Regarding intracerebral hemorrhage (ICH), Cerebrovascular Diseases published the 2006 European stroke initiative recommendations for the management of ICH. In 2009, the revised Japanese GLs for the management of stroke, including that of ICH, appeared in Japanese. Whereas GLs for the prevention and treatment of ischemic stroke were presented in detail, recommendations with regard to ICH are relatively rare both in Japan and Europe., Methods: Since 2011, the authors have met repeatedly and have compared the latest versions of published European and Japanese GLs for ischemic and hemorrhagic strokes. Many aspects have only been addressed in one but left out in the other GLs, which consequently founded the basis for the comparison. Classification of evidence levels and recommendation grades defined by the individual committees differed between both original GLs., Results: Aspects of major importance were similar and hence did not need extensive interpretation, mostly due to a lack of evidence from appropriate RCTs worldwide. The target level to which systolic blood pressure should be lowered is quite high; <170 mm Hg for patients with known hypertension in Europe and <180 mm Hg in Japan. The results of ongoing clinical trials are awaited for the optimal target level and optimal medications. Concerning ICH associated with oral anticoagulant therapy, both guidelines give similar recommendations, namely that anticoagulation should be discontinued and the international normalized ratio of prothrombin time should be normalized with prothrombin complex concentrate or fresh-frozen plasma and additional vitamin K. Patients with ICH were treated surgically, often based on individual decisions - more frequently in Japan, depending on the association with hypertension. Patients with large or intraventricular bleedings were only treated if a life-saving performance was considered, irrespective of the neurological outcome. Infra- and supratentorial differences were similarly addressed in both GLs., Conclusion: This brief survey - when compared with the lengthy original recommendations - provides a stimulating basis for an extended interest among Japanese and European stroke clinicians to learn from their individual experiences and to strengthen efforts for joint cooperation in treating and preventing stroke all around the globe., (Copyright © 2013 S. Karger AG, Basel.)

Background: Everolimus is approved for treatment of anti-vascular endothelial growth factor (VEGF)-refractory patients with metastatic renal cell carcinoma (mRCC). Clinical trials rarely mirror treatment reality. Thus, a broader evaluation of everolimus is valuable for routine use., Patients and Methods: A German multicenter non-interventional study documented mRCC patients starting everolimus after failure of initial VEGF-targeted therapy. Primary endpoint was effectiveness, defined as time to progression (TTP) according to investigator assessment (time from first dose to progression)., Results: Of 382 documented patients, 196 were included in this interim analysis. In the efficacy population (n = 165), median TTP was 7.0 months (95% confidence interval (CI) 5.1-9.0). Among patients with < or ≥ 6 months of previous VEGF-targeted therapy, median TTP was 6.6 months (95% CI 3.8-not estimable) and 7.4 months (95% CI 4.6-9.6), respectively. Most common adverse events were anemia (13%) and dyspnea (14%). Physicians assessed high tolerance and documented high adherence to everolimus therapy (approximately 97%)., Conclusion: In routine clinical practice, everolimus is effective, as measured by median TTP (longer than median progression-free survival in RECORD-1 trial), and well tolerated. Our results support everolimus use in anti-VEGF-refractory patients with mRCC., (Copyright © 2013 S. Karger AG, Basel.)

Background: The association of mortality and poor outcome with reduced levels of hemoglobin (Hb) and hematocrit (Hct) in patients admitted for ischemic stroke was recently demonstrated. The mechanisms behind this have remained unclear., Aims: Here, we aimed to investigate a putative association between low Hb and Hct levels and infarct growth., Methods: All consecutive patients who received intravenous thrombolysis based on multimodal magnetic resonance imaging during the years 1998-2009 were screened. Laboratory data as well as admission magnetic resonance images and follow-up computed tomography scans of 257 patients were assessed. Overall, data of 100 patients were of sufficient quality and further analyzed., Results: Decrease in Hb and Hct as well as perfusion-weighted imaging volume, mismatch volume, and final infarct size on follow-up computed tomography were associated with infarct growth. A linear regression model revealed Hb decrease (β = 0.23, p = 0.02) to be a predictor of infarct growth, independent of mismatch volume (β = 0.27, p = 0.004) and minimum sodium (β = -0.21, p = 0.03), and adjusted to the non-predicting variables age, National Institute of Health Stroke Scale score, maximum leucocytes and C-reactive protein, blood glucose, and Hct decrease., Conclusion: Hb levels that decrease after admission independently predict infarct growth in thrombolyzed stroke patients. The clinical implications of this relationship remain to be investigated.

Atherosclerosis is a chronic progressive inflammatory disease which manifests in the arterial vascular tree. It is a major cause of cardiovascular morbidity and contributes significantly to mortality in the developed world. Triggers for this inflammatory process are elevated levels of cholesterol, bacterial infection and obesity. The immune response in atherosclerosis is essentially pro-atherogenic, leading to lipid accumulation and cellular changes within the arterial wall. Small-animal models of atherosclerosis are used to study the relevance of candidate factors (cells, genes, diets) in the development and progression of lesions. From a multidisciplinary viewpoint, there are challenges and limitations to this approach. Activation of complement determines or modifies the outcome of acute and chronic inflammation. This review dissects the role of complement in the early development as well as the progressive manifestation of murine atherosclerosis and the advances in knowledge provided by the use of specific mouse models. It gives a critical overview of existing models, analyses seemingly conflicting results obtained with complement-deficient mouse models, highlights the importance of interrelationships between pro-coagulpant activity, adipose tissue, macrophages and complement, and uncovers exciting avenues of topical research., (Copyright © 2011 S. Karger AG, Basel.)

Background: In default of a plausible and satisfactory causal treatment for hemorrhagic stroke, a role of matrix metalloproteinases (MMPs) in the pathogenesis of cerebrovascular diseases has recently been widely discussed. The well-known impact of MMPs on extracellular matrix destruction triggered by inflammation as a foundation for several diseases, including stroke, is very much in evidence. Newly, some additional aspects of MMP function considering their intracellular activity crucial for neuronal death following ischemic brain damage have emerged. The effect of blood-brain barrier disruption caused by MMPs on the prognosis in patients suffering from spontaneous intracerebral hemorrhage (ICH) has been of interest since it throws a new light upon the pathogenesis, course and possible therapeutic approaches for this least treatable and at the same time most life-threatening form of stroke. Hence, we primarily aimed to review the current clinical knowledge on the significance of metalloproteinase activation in the course of spontaneous intracranial hemorrhage in humans. We also provide a brief characterization of the MMP enzyme family and report on the latest findings on issues arising from experimental studies., Methods: A Medline search using the following key words was performed: matrix metalloproteinases + spontaneous intracerebral hemorrhage/intracranial hemorrhage/bleeding/hemorrhagic stroke. We accepted studies reporting on MMP expression in adult patients with spontaneous ICH, as well as its relation to radiological and clinical features and patients' outcome. For the final review, 18 clinical studies were considered. MMP inhibition was reviewed on the basis of 11 relevant experimental studies. Also, some relevant reports on the biology of MMPs and their pathophysiology in ICH were reviewed., Results and Conclusions: Many studies provide convincing evidence of a detrimental role of MMPs in ICH, stressing their association with neuroinflammation. The role of MMPs in hemorrhagic stroke appears critical for hematoma and brain edema growth as well as for neuronal death, which are understood as secondary brain injury and may have a considerable clinical impact. Although data on human spontaneous ICH are scarce and mostly based on small populations, they reveal the apparent correlation between MMPs and clinical and radiological ICH features as well as the functional outcome, which might rationalize future therapeutic strategies. However, attempts at MMP inhibition in spontaneous ICH have solely been made under experimental conditions and were associated with a wide range of possible side effects. Therefore, further comprehensive, elucidating investigations in this field are vital before any conclusions could be translated to humans., (Copyright © 2012 S. Karger AG, Basel.)

Over 2 million people are affected by intracerebral haemorrhage (ICH) worldwide every year, one third of them dying within 1 month, and many survivors being left with permanent disability. Unlike most other stroke types, the incidence, morbidity and mortality of ICH have not declined over time. No standardised diagnostic workup for the detection of the various underlying causes of ICH currently exists, and the evidence for medical or surgical therapeutic interventions remains limited. A dedicated European research programme for ICH is needed to identify ways to reduce the burden of ICH-related death and disability. The European Research Network on Intracerebral Haemorrhage EURONICH is a multidisciplinary academic research collaboration that has been established to define current research priorities and to conduct large clinical studies on all aspects of ICH., (Copyright © 2011 S. Karger AG, Basel.)

Background: We report a treatment option in surgical therapy of locally advanced renal cell carcinoma (RCC)., Method: A 63-year-old patient with locally advanced RCC including an atrial thrombus underwent 2 cycles of neoadjuvant therapy (Sutent 50 mg daily for 4 weeks followed by 2 weeks off) and then tumor surgery. Primary surgical therapy had to be delayed because of suspected bronchial carcinoma and additional diagnostics. After neoadjuvant therapy to downsize the tumor thrombus and exclusion of any additional malignant tumors, operation was done via abdominal access; no sternotomy was necessary., Results: Histopathological examinations of the primary tumor after tyrosine kinase inhibitor therapy were evaluated and compared to tumor biopsy material taken before therapy., Conclusion: Neoadjuvant therapy with Sutent may represent a favorable treatment option in cases of locally advanced clear-cell RCC with extended tumor thrombus., (Copyright (c) 2010 S. Karger AG, Basel.)

Background: Acute hypertension frequently occurs in acute stroke and is associated with unfavorable outcome. However, despite the high prevalence, the pathophysiology remains unclear. Baroreflex dysfunction has repeatedly been reported in stroke patients. We hypothesize that blood pressure (BP) derangements in the acute phase relate to the impairment of baroreflex., Methods: We assessed baroreflex sensitivity (BRS) in 109 acute stroke patients with both ischemic and hemorrhagic stroke using the sequential cross-correlation method. Admission BP and BP values derived from continuous 72-hour monitoring were recorded. Demographic and clinical data including stroke volumes and admission NIHSS scores were included into the analysis., Results: The BRS significantly correlated with admission BP (r = -0.24, p = 0.01), with the occurrence of acute hypertension (> or =220mm Hg/ > or = 110 mm Hg) on admission (r = -0.37, p < 0.001) and with the number of episodes with > or =220 mm Hg/> or =110 mm Hg in the first 72 h after admission (r = -0.44, p < 0.001). Admission NIHSS or lesion volume did not correlate with acute hypertension on admission or hypertensive episodes within the first 72 h. In a multivariable model, BRS remained a significant, independent predictor for both the occurrence of acute hypertension on admission and hypertensive episodes within the first 72 h., Conclusions: In acute stroke, decreased BRS was independently associated with the occurrence of acute hypertension on admission. In addition, BRS seemed to be a valid predictor of the BP course in the first 72 h. As some antihypertensives may ameliorate BRS, therapeutic relevance of this finding warrants further attention., (Copyright (c) 2010 S. Karger AG, Basel.)

Background: Early prediction of outcome after decompressive surgery for space-occupying middle cerebral artery (MCA) infarction is needed to guide further therapy. Here we applied spectral EEG analysis to determine the prognosis early after hemicraniectomy, while the patient is still treated in the intensive care unit., Methods: Continuous EEG monitoring following hemicraniectomy was performed in 10 patients with space-occupying MCA infarction. All patients were analgosedated and mechanically ventilated. The first 6 h of monitoring after surgery were evaluated by spectral analysis. Outcome measures included Glasgow Outcome Scale (GOS), Level of Consciousness Scale (LOC) and National Institute of Health Stroke Scale (NIHSS) at discharge. Outcome after 3 months was assessed by modified Rankin Scale., Results: Six patients displayed a peak at 5-10 Hz in the EEG power spectrum. All these patients had a GOS score of 3 and an LOC score >or=7 at discharge. In contrast, the 4 patients without faster EEG activity had a GOS of 2 and LOC

Background: The aim of the current study was to assess the occurrence of infection and its impact on the short- and long-term outcome of patients with supratentorial intracerebral hemorrhage (ICH)., Methods: 247 patients suffering from supratentorial ICH were extracted from our local stroke database. Complete data sets including long-term functional outcome measured by the modified Rankin Scale (mRS), and baseline computed tomography data could be obtained in 113. The charts of these patients were screened for the presence and cause of infection, and baseline and maximal C-reactive protein (CRP) levels were recorded., Results: We identified 52 patients (50.5%) with infection during their hospital stay. Patients with infection, had significantly larger hemorrhages (28.7 vs. 11.9 ml; p = 0.002), a poorer admission status (National Institutes of Health Stroke Scale, NIHSS, score 14 vs. 6; p = 0.002) and more frequently intraventricular hemorrhage extension (46.2 vs. 23.5%; p = 0.016) than those without infection. In a multivariate logistic regression model, baseline NIHSS score (odds ratio, OR, 1.2, 95% confidence interval, CI, 1.1-1.31, p < 0.001), age (OR 1.1, 95% CI 1.03-1.16, p = 0.002) and maximal CRP levels (OR 1.72, 95% CI 1.12-2.64, p = 0.013) were independent predictors of poor long-term functional outcome (mRS >2)., Conclusion: Infections were frequent complications in our cohort of ICH patients and occurred significantly more often in patients with poor functional outcome. Maximal CRP levels were an independent predictor of poor outcome in a multivariate model.

Background: The outcomes after stroke vary considerably between countries, yet the extent of the variation after intracerebral hemorrhage (ICH) remains unknown. This study examines differences in outcomes after ICH in a recent multinational trial, and explores the effect of differences in patient severity and case management for the variations observed., Methods: Factor Seven for Acute Hemorrhagic Stroke was a randomized, multinational, double-blind, placebo-controlled trial conducted between May 2005 and February 2007 at 122 sites in 22 countries. We investigated differences in baseline patient characteristics, case management and clinical outcomes across the 14 highest recruiting countries. Between-country differences in mortality and functional outcomes were examined using regression analysis while adjusting for differences in observed patient severity (case mix) and case management., Results: Eight hundred and one patients had complete data on baseline characteristics, case management and clinical outcomes and were recruited in a country that contributed >or=20 patients to the trial. Significant differences were observed between the countries in unadjusted mortality rates (p = 0.001) and functional outcomes (p = 0.001) at 90 days after ICH onset. When first adjusting for differences in case mix, and secondly differences in case management, the differences in outcomes remained significant, yet the variation between countries was reduced with each level of adjustment. Significant determinants of mortality were age, baseline ICH and intraventricular hemorrhage volume, baseline neurological deficit, smoking status, use of mechanical ventilation, total length of hospital stay, reduction in blood pressure between 1 and 20% during the first 24 h of admission and edema management. Poor functional outcomes were also determined by age, baseline ICH volume and baseline neurological deficit as well as neurosurgical procedures performed and sedation during the first 5 days of admission., Conclusion: Significant global differences exist in the clinical outcomes after ICH, even after comprehensively adjusting for differences in case mix and case management. This is most likely due to unmeasured variation in case mix and case management. Similar research is encouraged in data sets of other multinational stroke trials to further investigate country-level and regional differences in clinical outcomes., ((c) 2009 S. Karger AG, Basel.)

Background: We recently demonstrated that recombinant activated factor VII (rFVIIa) given to patients presenting within 3 h of acute spontaneous intracerebral hemorrhage (ICH) reduces mortality (18% vs. 29%) and poor outcome (modified Rankin Scale, mRS, 4-6, 53 vs. 69%). This analysis was performed to determine the impact of rFVIIa on health-related quality of life (HRQoL) in those patients., Methods: In a prospective, randomized controlled trial, 399 patients (mean age, 66 years) received placebo, 40, 80 or 160 microg/kg of rFVIIa within 4 h of acute ICH. At 90 days, HRQoL was assessed with the EuroQoL (EQ-5D), a 5-dimensional measure of health which also includes the Visual Analogue Scale. Additionally, each level of the 90-day mRS was adjusted, using 4 different previously published utility values, to obtain a clearer picture of perceived HRQoL., Results: Among the 5 dimensions of EQ-5D, only mobility rating was significantly better for rFVIIa-treated patients (serious problems, 34 vs. 54%; p = 0.01). Yet, the utility value (scaled 1.0 = perfect health and 0.0 = dead) associated with the composite EQ-5D demonstrated significantly better HRQoL (0.48 vs. 0.36; p = 0.01). This was also true for the EQ-5D Visual Analogue Scale score (44 vs. 36; p = 0.04). Finally, all 4 algorithms for applying utility scores to the mRS indicated that rFVIIa was associated with significantly better perceived HRQoL (all p < 0.006)., Conclusions: Treatment with rFVIIa within 4 h of acute spontaneous ICH improves HRQoL.

This article represents the recommendations for the management of spontaneous intracerebral haemorrhage of the European Stroke Initiative (EUSI). These recommendations are endorsed by the 3 European societies which are represented in the EUSI: the European Stroke Council, the European Neurological Society and the European Federation of Neurological Societies., (Copyright 2006 S. Karger AG, Basel.)

Microdialysis is a means of measuring neurochemical changes in the extracellular space and has been applied in acute brain trauma, subarachnoid hemorrhage and stroke patients. In this study, we monitored neurochemical changes in the extracellular space using microdialysis in a patient with left-sided hemispheric infarction treated with moderate hypothermia (33 degrees C). Microdialysis probes were obtained from the infarcted and noninfarcted hemisphere during hypothermia and rewarming. Concentrations of extracellular substances in the infarcted hemisphere (glutamate, glycerine, lactate/pyruvate) decreased with hypothermia and remained stable (glutamate) or increased (glycerine, lactate/pyruvate) during rewarming. Concentrations of these substances in the noninfarcted hemisphere remained at normal levels. Microdialysis monitoring of therapeutic hypothermia in severe hemispheric infarction might be a useful additional monitoring tool to assess the status of the brain and to predict further deterioration., (Copyright 2001 S. Karger AG, Basel)

Modulation of immunomechanisms by tumor cells can be caused by secretion of cytokines. In vitro data are usually gained in culture systems. It is debatable whether these systems are representative of the conditions inside the respective tumor tissues. Immunohistochemical studies of tumor tissue cryostats were compared with those in matched primary renal cell carcinoma tumor cell cultures. Results were correlated with histopathological characteristics and the in vitro cytotoxic effect of autologous tumor infiltrating lymphocytes (TILs). Expression of all studied cytokines and cytokine receptors could be shown in cryostats and cell cultures, but the detection pattern varied individually. The immunohistochemical results in cryostats were in good accordance with those in cell cultures. Expression of TGFbeta1 both in cryostats and cell cultures significantly correlated with the lack of cytotoxic activity of autologous TILs. Representative data can be obtained in tumor culture systems of primary renal cell carcinoma. TGFbeta1 secretion could play an important role in the interactions between tumor and cytotoxic cells., (Copyright 2001 S. Karger AG, Basel)

Purpose: The most worrying problem with renal cell carcinoma (RCC) seems to be the prediction of metastases by means of tumor-specific markers. Therefore, much effort is committed to the development of new markers., Materials and Methods: The level of latent transforming growth factor beta1 (TGF-beta1) was measured in plasma samples by ELISA. These samples were collected from patients with RCC before they underwent radical nephrectomy, from patients 1 h after extracorporeal lithotripsy, from patients with pyelonephritis, and from healthy controls., Results: In all cases of RCC the levels of latent TGF-beta1 in plasma were much higher (n = 20, 41.0 +/- 13.9 ng/ml, range 19.3-78.1 ng/ml) than in healthy controls (n = 20, 3.8 +/- 2.9 ng/ml, range 0.6-9.9 ng/ml, p < 0.0001). The TGF-beta1 levels in plasma after extracorporeal lithotripsy (n = 20, 7.4 +/- 4. 64 ng/ml, range 2.9-21.7 ng/ml, p < 0.01) and in patients suffering from pyelonephritis (n = 20, 18.93 +/- 14.2 ng/ml, range 4.2-46.7 ng/ml, p < 0.001) were also higher than in healthy controls., Conclusion: We conclude that increased levels of latent TGF-beta1 are common in the plasma of RCC patients. The TGF-beta1 plasma level in RCC was found to be significantly higher than in cases of inflammation. Thus, TGF-beta1 is a possible tumor-prognostic marker in RCC.

Objectives: (1) To determine whether and how outcome measurements in the ECASS trial are influenced by a shorter time window (0-3 vs. 3-6 h) between onset of symptoms and start of thrombolytic therapy using recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke. (2) To discuss the results of the ECASS 0- to 3-hour cohort with the results of the National Institute of Neurological Disorders and Stroke Study (NINDSS)., Design and Analysis: Analysis of the 0- to 3-hour and the 3- to 6-hour cohort in accordance with the ECASS protocol. Comparative analysis of the ECASS and NINDSS results following the NINDSS protocol using dichotomized endpoints., Main Outcome Measures: Primary endpoints: modified Rankin Scale, Barthel Index; secondary endpoints: combined Barthel/Rankin, long-term Scandinavian Stroke Scale, National Institutes of Health Stroke Scale, mortality at 30 and 90 days, occurrence of intracranial hemorrhage. NINDS trial endpoint: favorable outcome as defined in the NINDS trial., Results: In ECASS, 87 patients were randomized within 3 h of stroke onset. Differences in favor of rt-PA treatment can be found for all primary and secondary outcome measures in the ECASS 0- to 3-hour cohort, except for mortality at day 30, which is somewhat higher in the rt-pA-treated group. However, due to the small sample size, the differences do not reach statistical significance. Early infarct signs (as defined by the ECASS protocol) are found as early as 2 h after stroke onset. Parenchymal hemorrhages are found significantly more often among rt-PA-treated patients. The results in the ECASS 0- to 3-hour cohort fit well with the results in NINDSS., Conclusion: Data from the 3-hour ECASS cohort support the efficacy of early thrombolytic therapy in acute hemispheric stroke patients. Comparing bleeding complications between the ECASS and NINDSS is difficult because of differences in the definition and occurrence of hemorrhagic events.

A reduction in neuronal damage following acute ischaemic stroke can be achieved by two major strategies: restoration of cerebral blood flow through the use of thrombolytics, and inhibition of the pathophysiological cascade that occurs as a result of a decreased cerebral blood flow through the use of neuroprotective agents. Therefore, combination therapy with thrombolytic and neuroprotective agents may provide additional benefits to those that can be achieved using the individual agents alone. Indeed, such benefits have already been demonstrated in several animal studies. However, a number of problems in trial design and statistical methodology need to be overcome. Nevertheless, combination therapy offers the potential of reducing the cost of stroke in terms of both health care and social welfare, and as well as limiting disability.