Borgerding A.,University of Gottingen |
Hasenkamp J.,University of Gottingen |
Engelke M.,University of Gottingen |
Burkhart N.,University of Gottingen |
And 3 more authors.
Experimental Hematology | Year: 2010
Objective: Antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells is a major effector mechanism of the monoclonal anti-CD20 antibody rituximab in eliminating B-cell lymphomas. Resistance to this treatment occurs, although CD20 antigen is expressed on the tumor cells. Materials and Methods: A model of ADCC was established by stimulating human bulk NK cells and inhibitory killer immunoglobulin receptor (KIR)-defined NK cells from human leukocyte antigen (HLA)-typed donors. NK-cell activation was triggered via stimulation of the Fc receptor with immunoglobulin G aggregates, rituximab-labeled HLA-defined CD20-positive B-lymphoblast cell lines or CD20-positive B-lymphoma cell lines. The effect of KIR ligation by anti-KIR antibodies and HLA, the HLA expression density and rituximab concentrations on the efficacy of ADCC were analyzed in granzyme B ELISPOT measuring NK-cell activation and fluorescein-activated cell sorting cytotoxicity assay. Results: HLA, but not CD20 expression density correlated with NK-cell activity against rituximab-labeled targets. ADCC was increased or decreased following HLA shielding or KIR activation by anti-KIR antibodies, respectively. Herein we show that rituximab-induced ADCC is attenuated upon ligation of KIR by HLA molecules expressed on human B-lymphoma target cells. Moreover, anti-KIR antibodies do not only block KIR/HLA interactions, but display agonistic effects at the KIR, which has to be considered for therapeutical applications. Conclusion: KIR activation and HLA expression density are critical determinants for the efficacy of rituximab treatment. An explanation for the failure of rituximab treatment may be the protection of the tumor cells from ADCC by inhibiting NK-cell function with their surface HLA. © 2010 ISEH - Society for Hematology and Stem Cells.
Frosch K.-H.,Asklepios Clinic St Georg |
Schmeling A.,Asklepios Clinic St Georg
Archives of Orthopaedic and Trauma Surgery | Year: 2016
To date there is no classification of patellar dislocations considering clinical and radiological pathologies. As a result many studies mingle the dislocation’s underlying pathologies, so that there are no consistent therapy recommendations. It is this article’s objective to introduce a patellar dislocation classification based on the current literature to allow for the application of a structured diagnosis and treatment algorithm. The classification is based on instability criteria as well as on clinical and radiological analyses of maltracking and on loss of patellar tracking. There are five types of patellar instability and maltracking. The rare type 1 is a simple (traumatic) patellar dislocation without maltracking and instability with a low risk of redislocation. Type 2 has a high risk of redislocation after primary dislocation; there is no maltracking. Here, a stabilising operation (in most cases MPFL reconstruction) is indicated and sufficient. Type 3 shows both instability and maltracking. Maltracking is mainly caused by: (a) soft tissue contracture, (b) patella alta, (c) pathological tibial tuberosity–trochlea groove distance, (d) valgus deviations and (e) torsional deformities. Stabilisation by means of isolated MPFL reconstruction is not sufficient in these types and additional osseous corrective surgeries are required to achieve physiological patellar tracking and to prevent redislocation. Type 4 features a highly unstable “floating patella” with complete loss of tracking caused by severe trochlear dysplasia. Therapy of choice is trochleoplasty, and if necessary combined with bony and soft-tissue procedures. Type 5 shows a patellar maltracking without instability. Maltracking can only be fixed by means of corrective osteotomy. The classification is referenced to current literature and each type is introduced by a case example. The resulting treatment consequence is also presented. © 2015, Springer-Verlag Berlin Heidelberg.
Bahlmann E.,Asklepios Clinic St Georg |
Gerdts E.,University of Bergen |
Cramariuc D.,University of Bergen |
Gohlke-Baerwolf C.,Herz Zentrum Bad Krozingen |
And 6 more authors.
Circulation | Year: 2013
Background-: Aortic valve area index adjusted for pressure recovery (energy loss index [ELI]) has been suggested as a more accurate measure of aortic stenosis (AS) severity, but its prognostic value has not been determined in a prospective study. Methods and Results-: The relation between baseline ELI and rate of aortic valve events and combined total mortality and hospitalization for heart failure resulting from the progression of AS was assessed by multivariate Cox regression and reclassification analysis in 1563 patients with initial asymptomatic AS in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. During 4.3 years follow-up, a total of 498 aortic valve events and 181 combined total mortalities and hospitalizations for heart failure caused by the progression of AS occurred. In Cox regression analyses, 1-cm2/m 2 lower baseline ELI predicted a 2-fold higher risk both for aortic valve events and for combined total mortality and hospitalization for heart failure independently of baseline peak aortic jet velocity or mean aortic gradient and independently of aortic root size (all P<0.05). In reclassification analysis, ELI improved the prediction of aortic valve events by 13% (95% confidence interval, 5-19), whereas the prediction of combined total mortality and hospitalization for heart failure resulting from the progression of AS did not improve significantly. Conclusions-: In asymptomatic AS patients without known atherosclerotic disease or diabetes mellitus, ELI provides independent and additional prognostic information to that derived from conventional measures of AS severity, suggesting that ELI should be measured in such patients. Clinical Trial Registration Information-: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00092677. © 2013 American Heart Association, Inc.
Quarch V.M.A.,Asklepios Clinic St Georg |
Enderle E.,Asklepios Clinic St Georg |
Lotz J.,University of Gottingen |
Frosch K.-H.,Asklepios Clinic St Georg
Archives of Orthopaedic and Trauma Surgery | Year: 2014
Introduction: Because of the potential donor site morbidity, cartilage lesions of more than 3 cm2 in size are considered to be critical regarding autologous osteochondral transplantation (OCT). In this study, the potential donor site morbidity for large defects should be reduced by means of OBI TruFit Plugs. Materials and methods: An autologous OCT was carried out on 37 patients and the cylinders were received from the dorsal medial femoral condyle. The donor site defects of 21 patients (average defect size 5.5 cm 2) were filled with artificial TruFit cylinders (study group); the donor site defects (average defect size 4.6 cm2) were left untreated for 16 patients. Results: In the study group, the Tegner, Western Ontario and McMaster Universities (WOMAC), knee society score, and visual analogue scale pain scores improved from preoperatively 3.2 (±0.8), 60.9 (±41.6), 133.6 (±27.1), and 4.8 (±2.3) points, respectively, to 3.9 (±0.6), 35.5 (±27.1), 177.8 (±16.6), and 3.3 (±2.9) points, respectively, at the time of the second follow-up; the control group's preoperative score values came to 2.8 (±0.9), 73.3 (±50.2), 123.8 (±41.5), and 5.3 (±2.7) points, respectively, and changed to 3.6 (±0.8), 41.4 (±28.8), 179.3 (±17.5), and 3.1 (±2.0) points, respectively, at the time of the second follow-up. The smaller the initial chondral defect was in the study group, the better the WOMAC score values became (p < 0.05). The modified Henderson score at the study group's donor sites improved from 19.2 (±3.3) to 13.7 (±2.1) points (p < 0.001); the control group's score values for the donor sites were 18.3 (±3.4) and 15.4 (±4.4) points (p = 0.0015). Conclusions: OCT is an effective therapy even for large chondral defects >3 cm2. By filling the defects with TruFit implants, no clinical improvements could be found since the donor site morbidity was already low anyway. However, the regeneration of defects filled with TruFit implants took more than 2 years. © 2014 Springer-Verlag.
Frosch K.-H.,Asklepios Clinic St Georg |
Frosch K.-H.,University of Gottingen |
Balcarek P.,Asklepios Clinic St Georg |
Walde T.,Asklepios Clinic St Georg |
Sturmer K.M.,Asklepios Clinic St Georg
Journal of Orthopaedic Trauma | Year: 2010
The selection of a surgical approach for the treatment of tibia plateau fractures is an important decision. Approximately 7% of all tibia plateau fractures affect the posterolateral corner. Displaced posterolateral tibia plateau fractures require anatomic articular reduction and buttress plate fixation on the posterior aspect. These aims are difficult to reach through a lateral or anterolateral approach. The standard posterolateral approach with fibula osteotomy and release of the posterolateral corner is a traumatic procedure, which includes the risk of fragment denudation. Isolated posterior approaches do not allow sufficient visual control of fracture reduction, especially if the fracture is complex. Therefore, the aim of this work was to present a surgical approach for posterolateral tibial plateau fractures that both protects the soft tissue and allows for good visual control of fracture reduction. The approach involves a lateral arthrotomy for visualizing the joint surface and a posterolateral approach for the fracture reduction and plate fixation, which are both achieved through one posterolateral skin incision. Using this approach, we achieved reduction of the articular surface and stable fixation in six of seven patients at the final follow-up visit. No complications and no loss of reduction were observed. Additionally, the new posterolateral approach permits direct visual exposure and facilitates the application of a buttress plate. Our approach does not require fibular osteotomy, and fragments of the posterolateral corner do not have to be detached from the soft tissue network. © 2010 Lippincott Williams & Wilkins.