Haus, Germany
Haus, Germany

Time filter

Source Type

Fiehler J.,University of Hamburg | Bakke S.J.,University of Oslo | Clifton A.,St George's, University of London | Houdart E.,University Paris Diderot | And 4 more authors.
Neuroradiology | Year: 2010

Three randomised controlled trials (RCTs) comparing outcomes after carotid artery stenting (CAS) with carotid endarterectomy (CEA) have recently been published. Recent systematic reviews have recommended that CAS is no longer justified for patients suitable for CEA. Indeed, in many centres, pooled data of RCTs show higher peri-operative risk of performing CAS vs. CEA with comparable long-term efficacy. Due to limitations in SPACE, EVA3S and ICSS study design and conduct, the inferiority of CAS to CEA as a method remains inconclusive. The goal of this review is not to discredit these trials but to develop a more differentiated and critical interpretation of the data and to create more discussion. It will discuss the necessity of RCTs for Interventional Neuroradiology in general and particular problems in study design (non-inferiority design and interpretation of results, clinical equipoise, study endpoints), practical study conduct difficulties (operator and centre experience, antiaggregation, timing of treatment) and the interpretation of the results (relation of internal and external validity, procedural complexity, the 68-year surprise, longer-term outcome). A premature rejection of CAS based on the data from these studies could harm future patients who would have had benefited from this procedure. For the time being, there is no reason why centres with good and independently controlled track records should stop performing CAS. Designing a single cooperative European trial that incorporates the lessons learned would be major step forward. © 2010 Springer-Verlag.


Wruck C.J.,RWTH Aachen | Fragoulis A.,RWTH Aachen | Gurzynski A.,Ear | Brandenburg L.-O.,RWTH Aachen | And 7 more authors.
Annals of the Rheumatic Diseases | Year: 2011

Objectives: Increasing evidence suggests that oxidative stress may play a key role in joint destruction due to rheumatoid arthritis (RA). The aim of this study was to elucidate the role of nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that maintains the cellular defence against oxidative stress, in RA. Methods: The activation status of Nrf2 was assessed in synovial tissue from patients with RA using immunohistochemistry. Antibody-induced arthritis (AIA) was induced in Nrf2-knockout and Nrf2-wild-type control mice. The severity of cartilage destruction was evaluated using a damage score. The extent of oxidative stress, the activation state of Nrf2 and the expression level of Nrf2 target genes were analysed by immunhistological staining. The expression of vascular endothelial growth factor (VEGF)-A was examined on mRNA and protein using the Luminex technique. A Xenogen imaging system was used to measure Nrf2 activity in an antioxidant response element-luciferase transgenic mouse during AIA. Results: Nrf2 was activated in the joints of arthritic mice and of patients with RA. Nrf2-knockout mice had more severe cartilage injuries and more oxidative damage, and the expression of Nrf2 target genes was enhanced in Nrf2-wild-type but not in knockout mice during AIA. Both VEGF-A mRNA and protein expression was upregulated in Nrf2-knockout mice during AIA. An unexpected finding was the number of spontaneously fractured bones in Nrf2-knockout mice with AIA. Conclusion: These results provide strong evidence that oxidative stress is significantly involved in cartilage degradation in experimental arthritis, and indicate that the presence of a functional Nrf2 gene is a major requirement for limiting cartilage destruction.


PubMed | Laboratory of Experimental Oncology, Institute of Immunology, Community Hospital Kiel, UKSH Campus Kiel and 2 more.
Type: Journal Article | Journal: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] | Year: 2016

Pancreatic ductal adenocarcinoma (PDAC) still has a poor prognosis and current treatments including immunotherapy often fail. This might be due to the pronounced immunosuppressive milieu impairing infiltration and function of immune effector cells. This study aimed at a comprehensive analysis of immune cells in PDAC patients by determining absolute and relative peripheral blood cell numbers of immune cell subsets along with their functional capacity.Whole blood cells or isolated peripheral blood mononuclear cells were characterized by flow cytometry. PDAC tissues were analyzed by immunohistochemistry. Anti-tumor activity of immune effector cells was determined by RTCA system.Our data demonstrate that relative CD4Monitoring immune cells along with the determination of their functional capacity provides a comprehensive assessment as a prerequisite for a personalized immunotherapeutic PDAC treatment.


PubMed | Ludwig Maximilians University of Munich, TU Munich, UKSH Campus Kiel and University of Heidelberg
Type: Journal Article | Journal: European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery | Year: 2016

Because of recent advances in best medical treatment (BMT), it is currently unclear whether any additional surgical or endovascular interventions confer additional benefit, in terms of preventing late ipsilateral carotid territory ischemic stroke in asymptomatic patients with significant carotid stenoses. The aim was to compare the stroke-preventive effects of BMT alone, with that of BMT in combination with carotid endarterectomy (CEA) or carotid artery stenting (CAS) in patients with high grade asymptomatic extracranial carotid artery stenosis.SPACE-2 was planned as a three-armed, randomized controlled trial (BMT alone vs. CEA plus BMT vs. CAS plus BMT, ISRCTN 78592017). However, because of slow patient recruitment, the three-arm study design was amended (July 2013) to become two parallel randomized studies (BMT alone vs. CEA plus BMT, and BMT alone vs. CAS plus BMT).The change in study design did not lead to any significant increase in patient recruitment, and trial recruitment ceased after recruiting 513 patients over a 5 year period (CEA vs. BMT (n=203); CAS vs. BMT (n=197), and BMT alone (n=113)). The 30 day rate of death/stroke was 1.97% for patients undergoing CEA, and 2.54% for patients undergoing CAS. No strokes or deaths occurred in the first 30 days after randomization in patients randomized to BMT. There were several potential reasons for the low recruitment rates into SPACE-2, including the ability for referring doctors to refer their patients directly for CEA or CAS outwith the trial, an inability to convince patients (who had come mentally prepared that an intervention was necessary) to accept BMT, and other economic constraints.Because of slow recruitment rates, SPACE-2 had to be stopped after randomizing only 513 patients. The German Research Foundation will provide continued funding to enable follow up of all recruited patients, and it is also planned to include these data in any future meta-analysis prepared by the Carotid Stenosis Trialists Collaboration.


Krause-Titz U.R.,UKSH Campus Kiel | Warneke N.,University of Munster | Freitag-Wolf S.,Institute of Medical Informatics and Statistics | Barth H.,UKSH Campus Kiel | Mehdorn H.M.,UKSH Campus Kiel
Neurosurgical Review | Year: 2016

After performing a decompressive craniectomy, a cranioplastic surgery is usually warranted. The complications of this reconstructive procedure may differ from the initial operation. The authors of this study report on their experience to define patient-specific and procedural risk factors for possible complications following cranioplasty influencing the outcome (Glasgow Outcome Scale (GOS)), mobility, shunt dependency, and seizures. A retrospective analysis of 263 patients of all ages and both sexes who had undergone cranioplasty after craniectomy for traumatic brain injury (including chronic subdural hematoma), subarachnoidal hemorrhage (including intracerebral hemorrhage), ischemic stroke, and tumor surgery in one single center in 12 years from January 2000 to March 2012 has been carried out. A multiple logistic regression analysis was performed to identify potential risk factors (age, gender, used cranioplasty material, initial diagnosis, clipped or coil-embolized subarachnoidal hemorrhage (SAH) patients, time interval, complications especially hydrocephalus and seizures, mobility) upon the prognosis described as a dichotomized Glasgow Outcome Scale. Two hundred forty-eight patients met the study criteria. The overall complication rate after cranioplastic surgery was 18.5 % (46 patients). Complications included: surgical site infection, epidural hematoma, hydrocephalus with or without former SAH, and new-onset seizures. Logistic regression analysis identified significant correlation between a low GOS (2 or 3) and postoperative seizures (OR 2.37, CI 1.35–4.18, p < 0.05), shunt-depending hydrocephalus (OR 5.83, CI 3.06–11.11, p < 0.05), and age between 51 and 70 years (OR 2.4, 95 % CI 1.09–5.29, p = 0.029). However, gender, time interval between craniectomy and cranioplasty, initial diagnosis, and used cranioplasty material had no significant influence on post-cranioplasty complications as surgical site infections, hematoma, wound healing disturbance, seizures, or hydrocephalus. Evaluation of treatment modality in aneurysmal SAH clip vs. coil showed no significant relation to postoperative complications either. Complications after cranioplastic surgery are a common problem, as prognostic factors could identify a shunt-depending hydrocephalus and epilepsia to develop a major deficit after cranioplastic surgery (GOS 2 or 3). We detected a significant extra risk of people between the age of 51 and 70 years to end up in GOS level 2 or 3. © 2015, Springer-Verlag Berlin Heidelberg.


Grage-Griebenow E.,Institute for Experimental Medicine | Jerg E.,Institute for Experimental Medicine | Gorys A.,Institute for Experimental Medicine | Wicklein D.,Institute for Anatomy and Experimental Morphology | And 11 more authors.
Molecular Oncology | Year: 2014

Regulatory T cell (T-reg) enrichment in the tumor microenvironment is regarded as an important mechanism of tumor immune escape. Hence, the presence of T-regs in highly malignant pancreatic ductal adenocarcinoma (PDAC) is correlated with short survival. Likewise, the adhesion molecule L1CAM is upregulated during PDAC progression in the pancreatic ductal epithelium also being associated with poor prognosis. To investigate whether L1CAM contributes to enrichment of T-regs in PDAC, human CD4+CD25+CD127-CD49d- T-regs and CD4+CD25- T-effector cells (T-effs) were isolated by magnetic bead separation from blood of healthy donors. Their phenotype and functional behavior were analyzed in dependence on human premalignant (H6c7) or malignant (Panc1) pancreatic ductal epithelial cells, either exhibiting or lacking L1CAM expression. T cells derived from blood and tumors of PDAC patients were analyzed by flow cytometry and findings were correlated with clinical parameters. Predominantly T-regs but not T-effs showed an increased migration on L1CAM expressing H6c7 and Panc1 cells. Whereas proliferation of T-regs did not change in the presence of L1CAM, T-effs proliferated less, exhibited a decreased CD25 expression and an increased expression of CD69. Moreover, these T-effs exhibited a regulatory phenotype as they inhibited proliferation of autologous T cells. Accordingly, CD4+CD25-CD69+ T cells were highly abundant in PDAC tissues compared to blood being associated with nodal invasion and higher grading in PDAC patients. Overall, these data point to an important role of L1CAM in the enrichment of immunosuppressive T cells in particular of a CD4+CD25-CD69+-phenotype in PDAC providing a novel mechanism of tumor immune escape which contributes to tumor progression. © 2014 Federation of European Biochemical Societies.


Helm O.,Institute for Experimental Medicine | Held-Feindt J.,UKSH Campus Kiel | Schafer H.,Laboratory of Molecular Gastroenterology and Hepatology | Sebens S.,Institute for Experimental Medicine
OncoImmunology | Year: 2014

We recently identified tumor-associated macrophages from pancreatic ductal adenocarcinoma sharing pro- and anti-inflammatory characteristics. Already in residence in the setting of chronic pancreatitis, local macrophages confer malignancy-associated features to premalignant pancreatic ductal epithelial cells by both promoting and inhibiting inflammation, either of which can foster malignant conversion. Our findings support the concept that contrasting modes of inflammation can promote tumorigenesis. © 2014 Taylor & Francis Group, LLC.


PubMed | UKSH Campus Kiel, Institute of Medical Informatics and Statistics and University of Munster
Type: Journal Article | Journal: Neurosurgical review | Year: 2016

After performing a decompressive craniectomy, a cranioplastic surgery is usually warranted. The complications of this reconstructive procedure may differ from the initial operation. The authors of this study report on their experience to define patient-specific and procedural risk factors for possible complications following cranioplasty influencing the outcome (Glasgow Outcome Scale (GOS)), mobility, shunt dependency, and seizures. A retrospective analysis of 263 patients of all ages and both sexes who had undergone cranioplasty after craniectomy for traumatic brain injury (including chronic subdural hematoma), subarachnoidal hemorrhage (including intracerebral hemorrhage), ischemic stroke, and tumor surgery in one single center in 12 years from January 2000 to March 2012 has been carried out. A multiple logistic regression analysis was performed to identify potential risk factors (age, gender, used cranioplasty material, initial diagnosis, clipped or coil-embolized subarachnoidal hemorrhage (SAH) patients, time interval, complications especially hydrocephalus and seizures, mobility) upon the prognosis described as a dichotomized Glasgow Outcome Scale. Two hundred forty-eight patients met the study criteria. The overall complication rate after cranioplastic surgery was 18.5% (46 patients). Complications included: surgical site infection, epidural hematoma, hydrocephalus with or without former SAH, and new-onset seizures. Logistic regression analysis identified significant correlation between a low GOS (2 or 3) and postoperative seizures (OR 2.37, CI 1.35-4.18, p<0.05), shunt-depending hydrocephalus (OR 5.83, CI 3.06-11.11, p<0.05), and age between 51 and 70 years (OR 2.4, 95% CI 1.09-5.29, p=0.029). However, gender, time interval between craniectomy and cranioplasty, initial diagnosis, and used cranioplasty material had no significant influence on post-cranioplasty complications as surgical site infections, hematoma, wound healing disturbance, seizures, or hydrocephalus. Evaluation of treatment modality in aneurysmal SAH clip vs. coil showed no significant relation to postoperative complications either. Complications after cranioplastic surgery are a common problem, as prognostic factors could identify a shunt-depending hydrocephalus and epilepsia to develop a major deficit after cranioplastic surgery (GOS 2 or 3). We detected a significant extra risk of people between the age of 51 and 70 years to end up in GOS level 2 or 3.


Rohr A.C.,UKSH Campus Kiel | Riedel C.,UKSH Campus Kiel | Fruehauf M.-C.,University of Kiel | Van Baalen A.,University of Kiel | And 5 more authors.
American Journal of Neuroradiology | Year: 2011

BACKGROUND AND PURPOSE: IH can alter the configuration of anatomic structures of the central nervous system. We determined the sensitivity and specificity of MR imaging to detect these changes in patients with secondary IH. MATERIALS AND METHODS: Patients (n = 36) with IH were prospectively investigated with MR imaging and were matched to 36 controls. MR images were evaluated for elongation and edema of the optic nerves, protrusion of the optic disc, flattening of the posterior sclera, height of the pituitary gland, and width of the optic nerve sheath. On MRV, we recorded venous sinus abnormalities and measured the luminal width of the superior ophthalmic veins. A grading score was introduced to define cranial venous outflow obstruction. RESULTS: Cranial venous outflow obstruction and ONS hydrops were the most valid signs indicating IH with a sensitivity of 94% and 92% and a specificity of 100% and 89%, respectively. Sensitivities and specificities were 56% and 97% for reduced pituitary height, 64% and 78% for flattening of the posterior sclera, 31% and 97% for widening of the superior ophthalmic veins, 33% and 100% for optic disc protrusion, 14% and 100% for optic nerve edema, and 6% and 100% for elongation of the optic nerve. At least 2 MR imaging findings could be demonstrated in each patient but in none of the controls. The number of positive MR imaging findings correlated with CSF pressure (r = 0.62, P = .01). CONCLUSIONS: The combination of cranial and orbital MR imaging and MRV can be highly sensitive and specific in the diagnosis of patients with IH.


Burger R.,UKSH Campus Kiel
Transfusion Medicine and Hemotherapy | Year: 2013

Almost 3 decades have passed since the discovery and cloning of IL-6, and a tremendous amount of work has contributed to the current knowledge of the biological functions of this cytokine, its receptor, and the signaling pathways that are activated. The understanding of the role of IL-6 in human disease has led to the development of novel therapeutic strategies that block the biological functions of IL-6. In clinical studies, IL-6 and IL-6 receptor antibodies have proven efficacy in rheumatoid arthritis, systemic juvenile idiopathic arthritis, and Castleman's disease, conditions that are known to be driven by IL-6. The focus of this overview is the role of IL-6 in the pathophysiology of hematological malignancies. © 2013 S. Karger GmbH, Freiburg.

Loading UKSH Campus Kiel collaborators
Loading UKSH Campus Kiel collaborators