Zugkraftmikroskopie an Osteoblasten

Knochenzellen sind in der Lage, mechanische Stimuli als Reiz aufzunehmen und darauf zu reagieren. Dieses zeigt sich in Umbauvorgängen der Knochenstruktur bei der mechanischen Belastung. Wie es allerdings vom dehnungsreiz bis zur zellulären Antwort von Osteoblasten kommt, ist noch Gegenstand aktueller Forschung. Diese sogenannte Mechanotransduktionskaskade ist ein wichtiger Ausgangspunktfür die Erforschung der Pathophysiologie der Osteoporose. Ziel dieser Arbeit war es, als Beitrag zur Aufklärung der Mechanotransduktionskaskade, auf zellulärer und subzellulärer Ebene die Interaktionskräfte von Osteoblasten mit ihrer Umgebung zu messen und Kraftverteilungsmuster zu beschreiben. Zudem sollte der Einfluss von einem elektrischen Feld auf die Kraftverteilungsmuster von Osteoblasten untersucht werden, um das Phänomen zu untersuchen, dass Osteoblasten sich in Zellkultur aktiv rechtwinklig zu den elektrischen Feldlinien ausrichten, wohingegen sich z.B. Neuronen parallel dazu ausrichten. Die Technik der Zugkraftmikroskopie wurde im Rahmen dieser Arbeit an die Gegebenheiten des hiesigen Labors und die zu beantwortenden Fragen angepasst. Es wurden Zellen auf flexiblen Polyacrylamidsubstraten kultiviert, so dass die zu messenden Interaktionskräfte zu detektierbaren Deformationen der Substrate führten. Durch das Analysieren der zellverursachten Substratdeformationen ließen sich die Ebenenprojektionen der verursachenden zellulären Kräfte sowohl zeitlich als auch quantitativ bestimmen. Die Deformationen wurden durch das Vergleichen eines Substratbildes zum jeweiligen Messzeitpunkt mit einem undeformierten Referenzbild ohne Zelle gemessen. Daraus konnte eine Matrix der Deformationsvektoren erstellt werden. Aus dieser wurden die Kraftvektoren berechnet. Bei der Bestimmung der gesamten auf das Substrat Kraft konnte ein signifikanter Unterschied zwischen primären bovinen Osteoblasten und Osteosarkomzellen festgestellt werden. Als Mittelwert der Gesamtkraft pro Zelle wurden für osteoblasten 660 nN und für MG63 Zellen nur 47 nN bestimmt

Acute ischemic stroke in a university hospital intensive care unit : 1-year costs and outcome

Background and purpose Little is currently known about the cost-effectiveness of intensive care of acute ischemic stroke (AIS). We evaluated 1-year costs and outcome for patients with AIS treated in the intensive care unit (ICU). Materials and methods A single-center retrospective study of patients admitted to an academic ICU with AIS between 2003 and 2013. True healthcare expenditure was obtained up to 1 year after admission and adjusted to consumer price index of 2019. Patient outcome was 12-month functional outcome and mortality. We used multivariate logistic regression analysis to identify independent predictors of favorable outcomes and linear regression analysis to assess factors associated with costs. We calculated the effective cost per survivor (ECPS) and effective cost per favorable outcome (ECPFO). Results The study population comprised 154 patients. Reasons for ICU admission were: decreased consciousness level (47%) and need for respiratory support (40%). There were 68 (44%) 1 year survivors, of which 27 (18%) had a favorable outcome. High age (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.91-0.98) and high hospital admission National Institutes of Health Stroke Scale score (OR 0.92, 95% CI 0.87-0.97) were independent predictors of poor outcomes. Increased age had a cost ratio of 0.98 (95% CI 0.97-0.99) per added year. The ECPS and ECPFO were 115,628euro and 291,210euro, respectively. Conclusions Treatment of AIS in the ICU is resource-intense, and in an era predating mechanical thrombectomy the outcome is often poor, suggesting a need for further research into cost-efficacy of ICU care for AIS patients.Peer reviewe

Carotid Embolectomy and Endarterectomy for Symptomatic Complete Occlusion of the Carotid Artery as a Rescue Therapy in Acute Ischemic Stroke

Emergency endarterectomy of an occluded internal carotid artery (ICA) has not been investigated as an option of rescue therapy for severe acute ischemic stroke in the era of intravenous (IV) thrombolysis treatment neither as a primary treatment nor after failed IV thrombolysis. Data from the pre-IV thrombolysis era are conflicting and therefore emergency endarterectomy has not been recommended. The number of patients reaching the emergency room within the IV thrombolysis time window has vastly grown due to advanced acute stroke treatment protocols. The efficacy of mechanical thrombectomy as a primary or add-on to IV thrombolysis therapy option is being actively investigated. We herein report 2 cases of acute ischemic stroke with computerized tomography (CT) angiography-documented occlusion of an ICA that were treated with emergency carotid endarterectomy and embolectomy to restore cerebral blood flow. Both cases presented with severe stroke symptoms and signs not responding to IV thrombolysis and showed severe CT-perfusion deficits mainly representing ischemic penumbra. Blood flow was surgically restored after 5 h of symptom onset. Both patients achieved a favorable outcome. We conclude that timely surgical approach of acute ICA occlusion after failed thrombolysis as a rescue therapy may be a viable option in well-selected patients

Intravenous thrombolysis for suspected ischemic stroke with seizure at onset

Objective Seizure at onset (SaO) has been considered a relative contraindication for intravenous thrombolysis (IVT) in patients with acute ischemic stroke, although this appraisal is not evidence based. Here, we investigated the prognostic significance of SaO in patients treated with IVT for suspected ischemic stroke. Methods In this multicenter, IVT-registry-based study we assessed the association between SaO and symptomatic intracranial hemorrhage (sICH, European Cooperative Acute Stroke Study II definition), 3-month mortality, and 3-month functional outcome on the modified Rankin Scale (mRS) using unadjusted and adjusted logistic regression, coarsened exact matching, and inverse probability weighted analyses. Results Among 10,074 IVT-treated patients, 146 (1.5%) had SaO. SaO patients had significantly higher National Institutes of Health Stroke Scale score and glucose on admission, and more often female sex, prior stroke, and prior functional dependence than non-SaO patients. In unadjusted analysis, they had generally less favorable outcomes. After controlling for confounders in adjusted, matched, and weighted analyses, all associations between SaO and any of the outcomes disappeared, including sICH (odds ratio [OR](unadjusted) = 1.53 [95% confidence interval (CI) = 0.74-3.14], ORadjusted = 0.52 [95% CI = 0.13-2.16], ORmatched = 0.68 [95% CI = 0.15-3.03], ORweighted = 0.95 [95% CI = 0.39-2.32]), mortality (ORunadjusted = 1.49 [95% CI = 1.00-2.24], ORadjusted = 0.98 [95% CI = 0.5-1.92], ORmatched = 1.13 [95% CI = 0.55-2.33], ORweighted = 1.17 [95% CI = 0.73-1.88]), and functional outcome (mRS >= 3/ordinal mRS: ORunadjusted = 1.33 [95% CI = 0.96-1.84]/1.35 [95% CI = 1.01-1.81], ORadjusted = 0.78 [95% CI = 0.45-1.32]/0.78 [95% CI = 0.52-1.16], ORmatched = 0.75 [95% CI = 0.43-1.32]/0.45 [95% CI = 0.10-2.06], ORweighted = 0.87 [95% CI = 0.57-1.34]/1.00 [95% CI = 0.66-1.52]). These results were consistent regardless of whether patients had an eventual diagnosis of ischemic stroke (89/146) or stroke mimic (57/146 SaO patients). Interpretation SaO was not an independent predictor of poor prognosis. Withholding IVT from patients with assumed ischemic stroke presenting with SaO seems unjustified. ANN NEUROL 2019Peer reviewe

Comparison of automated infarct core volume measures between non-contrast computed tomography and perfusion imaging in acute stroke code patients evaluated for potential endovascular treatment

Introduction: Patients with small core infarction and salvageable penumbra are likely to benefit from endovascular treatment (EVT). As computed tomography perfusion imaging (CTP) is not always available 24/7 for patient selection, many patients are transferred to stroke centers for CTP. We compared automatically measured infarct core volume (NCCTcore) from the non-contrast computed tomography (NCCT) with ischemic core volume (CTPcore) from CTP and the outcome of EVT to clarify if NCCTcore measurement alone is sufficient to identify patients that benefit from transfer to stroke centers for EVT. Patients and methods: We included all consecutive stroke-code patients imaged with both NCCT and CTP at Helsinki University Hospital during 9/2016-01/2018. NCCTcore and CTPcore volumes were automatically calculated from the acute NCCT images. Follow-up infarct volume (FIV) was measured from 24 h follow-up NCCT to evaluate efficacy of EVT. To study whether NCCTcore could be used to identify patients eligible to EVT, we subgrouped patients based on NCCTcore volumes (>50 mL and > 70 mL). Results: Out of 1743 patients, baseline NCCTcore, CTPcore and follow-up NCCT was available for 288 patients. Median time from symptom onset to baseline imaging was 74 min (IQR 52-118), and time to follow-up imaging 24.15 h (22.25-26.33). Baseline NCCTcore was 20 mL (10-42), CTPcore 4 mL (0-16), and FIV 5 mL (1-49). Out of 288 patients, 23 had NCCTcore > 70 mL and 26 had CTPcore > 70 mL. NCCTcore and CTPcore performed similarly well in predicting large FIV (>70 ml). Conclusion: NCCTcore is a promising tool to identify patients that are not eligible to EVT due to large ischemic cores at baseline imaging.Peer reviewe

EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry : basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry

Purpose The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry. Participants All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS). Findings to date Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups. Future plans This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements.Peer reviewe

EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry

PURPOSE The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry. PARTICIPANTS All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS). FINDINGS TO DATE Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups. FUTURE PLANS This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements

Recanalization treatment for acute ischemic stroke: 3-month outcome before and after implementation of routine endovascular treatment

Peer reviewe

Is the weekend effect true in acute stroke patients at tertiary stroke center?

Background: There is contradicting evidence on the outcome of emergency patients treated during weekends versus weekdays. We studied if outcome of ischemic stroke patients receiving intravenous thrombolysis (IVT) differs according to the treatment time. Methods: Our retrospective study included consecutive patients receiving IVT within 4.5 h of stroke onset between June 1995 and December 2018 at the Helsinki University Hospital. The patients were compared based on the treatment initiation either during weekdays (Monday to Friday) or weekend (Saturday and Sunday). The primary outcome was 3-month mortality and secondary outcomes comprised 3-month modified Rankin Scale (mRS) and incidence of symptomatic intracerebral hemorrhage (sICH). Additional analyses studied the effect of IVT treatment according to non-office hours, time of day, and season. Results: Of the 3980 IVT-treated patients, 28.0% received treatment during weekends. Mortality was similar after weekend (10.0%) and weekday (10.6%) admissions in the multivariable regression analysis (OR 0.78; 95% CI 0.59-1.03). Neither 3-month mRS (OR 0.98; 95% CI 0.86-1.12), nor the occurrence of sICH (4.2% vs 4.6%; OR 0.87; 95% CI 0.60-1.26) differed between the groups. No outcome difference was observed between the office vs non-office hours or by the time of day. However, odds for worse outcome were higher during autumn (OR 1.19; 95% CI 1.04-1.35) and winter (OR 1.15; 95% CI 1.01-1.30). Conclusion: We did not discover any weekend effect for IVT-treated stroke patients. This confirms that with standardized procedures, an equal quality of care can be provided to patients requiring urgent treatment irrespective of time.Peer reviewe

Extending thrombolysis to 4.5-9 h and wake-up stroke using perfusion imaging : a systematic review and meta-analysis of individual patient data

Markku Kaste tutkimusryhmän jäsenenäBackground Stroke thrombolysis with alteplase is currently recommended 0-4.5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4.5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis. Methods In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials. gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged =18 years) with ischaemic stroke treated more than 4.5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. Findings We identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1.86, 95% CI 1.15-2.99, p=0.011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9.7, 95% CI 1.23-76.55, p=0.031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1.55, 0.81-2.96, p=0.66). Interpretation Patients with ischaemic stroke 4.5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis. Copyright (c) 2019 Elsevier Ltd. All rights reserved.Peer reviewe