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Schafer U.,Asklepios Clinic St. Georg | Frerker C.,Asklepios Clinic St. Georg | Thielsen T.,Asklepios Clinic St. Georg | Schewel D.,Asklepios Clinic St. Georg | And 2 more authors.
EuroIntervention | Year: 2015

Aims: Hypertrophic obstructive cardiomyopathy (HOCM) with left ventricular outflow tract obstruction frequently involves a systolic anterior motion (SAM) of the anterior mitral leaflet. We hypothesised that SAM could be a new target for MitraClip therapy. Methods and results: Three patients with HOCM were chosen for MitraClip therapy, due to significant SAM with subsequent mitral regurgitation. Invasive haemodynamic studies (right heart catheterisation, simultaneous transaortic pressure recording, and administration of nitroglycerine) were performed before and after MitraClip implantation, and a six-week follow-up was undertaken. MitraClip implantation was successfully performed with significant reduction of mitral regurgitation and SAM in all patients. Basal peak gradients (before clip: 65±25.5 mmHg; after clip: 7.7±5.0 mmHg) as well as provoked pressure gradients (before clip: 145.3±8.1 mmHg; after clip: 23.2±7.6 mmHg) were significantly reduced after MitraClip implantation. Right heart catheterisation data did not reveal major changes. At six-week follow-up, all patients presented in a persistently improved clinical state (NYHA Class I-II) with insignificant residual MR and continuously reduced LVOT gradients. Conclusions: This is the first catheter-based study targeting primarily a SAM in HOCM to reduce LVOT obstruction. The results prove the concept that SAM is more than an epiphenomenon in HOCM. Thus, SAMinduced obstruction might be a valuable target for the MitraClip. © Europa Digital & Publishing 2015. All rights reserved.


Cramariuc D.,University of Bergen | Rogge B.P.,University of Bergen | Lonnebakken M.T.,University of Bergen | Boman K.,Umeaa University | And 5 more authors.
Heart | Year: 2015

Objective Women with severe aortic valve stenosis (AS) have better LV systolic function and more concentric LV geometry than their male counterparts. However, sex differences in cardiovascular (CV) outcome during progression of AS have not been reported from a longitudinal prospective study. Methods Doppler echocardiography and CV events were recorded during a median of 4.0 years in 979 men and 632 women aged 28-86 (mean 67±10) years in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study. LV systolic function was assessed by EF and midwall shortening (MWS). Study outcomes were ASrelated events, ischaemic CV events and total mortality. Results The annular cumulative incidence of AS events, ischaemic CV events and death was 8.1%, 3.4% and 2.8% in women, and 8.9%, 4.4% and 2.4% in men, respectively. Women and men had similar AS progression rate whether measured by peak jet velocity, mean gradient or valve area. In multivariate analyses, female sex independently predicted less reduction in LV MWS and EF during follow-up (both p<0.05). In time-varying Cox analyses, women had a 40% lower rate of ischaemic CV events (95% CI 21% to 54%), in particular, more than 50% lower rate of stroke and coronary artery bypass grafting, and a 31% lower allcause mortality (95% CI 1% to 51%), independent of active study treatment, age and hypertension, as well as time-varying valve area, low systolic function and abnormal LV geometry. AS event rate did not differ by sex. Conclusions In the SEAS study, women and men had similar rates of AS progression and AS-related events. However, women had lower total mortality and ischaemic CV event rate than men independent of confounders. Trial registration number ClinicalTrials.gov identi fier: NCT00092677. Funding The SEAS (Simvastatin Ezetimibe in Aortic Stenosis) Echocardiography Core Laboratory was supported by MSP Singapore Company, LLC, Singapore, a partnership between Merck Co, and the Schering-Plough Corporation.


Frosch K.-H.,Asklepios Clinic St. Georg | Preiss A.,Asklepios Clinic St. Georg | Heider S.,University of Gottingen | Stengel D.,University of Greifswald | And 3 more authors.
Knee Surgery, Sports Traumatology, Arthroscopy | Year: 2013

Purpose: Treatment of knee dislocation is still controversial. There is no evidence to favour ligament suture or reconstruction. Until now, no meta-analyses have examined suture versus reconstruction of cruciate ligaments in knee dislocations with respect to injury pattern and rupture classification. Methods: We searched Medline, the Cochrane Controlled Trial Database, and EMBASE for studies on surgical treatment for 'knee dislocation' and 'multiple ligament injured knee'. A meta-analysis was performed using individual patient data. Results: Nine studies including 195 patients (200 knees) with a mean age of 31.4 (±13) years fulfilled the study requirements. Thirteen cases of type II dislocations, 63 cases of type III medial, 84 cases of type III lateral, and 40 cases of type IV dislocations, according to Schenck's classification, were found. Poor or moderate results were found in 70 % of patients without surgical treatment of ACL or PCL (n = 27). Patients (n = 40) treated by sutures of the ACL and PCL demonstrated a significantly greater proportion of excellent or good results (40 and 37.5 %, respectively) (p < 0.001). Patients who underwent reconstruction of the ACL and PCL (n = 75) showed excellent or good results (28 and 45 %, respectively). No significant difference was found when comparing suture versus reconstruction of the ACL and PCL (n.s.). The outcome depends considerably on Schenck's injury pattern classification. Conclusion: Conservative treatment after knee dislocation yields poor clinical results. Suture repair of cruciate ligaments can still serve as an alternative option for multiligament injuries of the knee and achieve good clinical results, which are comparable to those of ligament reconstruction. The data provided by this meta-analysis should be reinforced by a prospective study, in which suture repair and ligament reconstruction are compared. Level of evidence: IV. © 2012 The Author(s).


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.


Albers K.,University of Hamburg | Schlein C.,University of Hamburg | Wenner K.,University of Hamburg | Lohse P.,Ludwig Maximilians University of Munich | And 4 more authors.
Atherosclerosis | Year: 2014

Deficiency of apoprotein A-V (apoA-V) can cause hypertriglyceridemia. In an 11 months old boy presenting with a severe hypertriglyceridemia, a formerly unknown 24 nucleotide deletion in exon 2 of the APOA5 gene was detected. The homozygous mutation results in an eight amino acid loss in the signal peptide sequence (c.16_39del; p.Ala6_Ala13del). Screening of control persons proved that this deletion is a rare mutation. Hypertriglyceridemia in the patient was only found at the time when he was breast fed, while after weaning, triglyceride levels were close to normal. Under both dietary conditions, apoA-V protein was undetectable in plasma while post-heparin plasma lipoprotein lipase activity was normal.Expression analysis of normal and mutated protein by Western blot and immunofluorescence in apoA-V deficient primary hepatocytes revealed that, due to changes in the signal peptide, mutated apoA-V was intracellularly missorted to lipid droplets and not secreted. Wild type apoA-V, instead, was not targeted to lipid droplets but transported via endosomal compartments to the plasma membrane for secretion.It is concluded that the c.16_39del mutation in the APOA5 gene leads to hepatic missorting and impaired secretion, which consequently results in undetectable apoA-V plasma levels. The absence of apoA-V in plasma leads under conditions of fat-rich diets to severe chylomicronemia, suggestive for a modulatory role of apoA-V for lipoprotein lipase mediated intravascular triglyceride lipolysis. © 2014 The Authors.


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.


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 | Akoto R.,Sports Traumatology | Heitmann M.,Asklepios Clinic St. Georg | Enderle E.,Asklepios Clinic St. Georg | And 2 more authors.
Knee Surgery, Sports Traumatology, Arthroscopy | Year: 2015

Purpose: With combined PCL reconstruction and a minimal invasive (extra-anatomical) Larson’s procedure, dorsal instability can be reduced by about 50–70 %. Better results are described by open and more anatomical procedures. In this study, a new, standardized, arthroscopic technique for anatomical popliteus tendon (PLT) reconstruction is evaluated. Methods: In 13 cadaver knees, an arthroscopic reconstruction of the PLT and the lateral collateral ligament was performed. Twelve defined landmarks were used for arthroscopic tunnel placement, and the distance of the tunnel locations to these specific landmarks was evaluated. Results: The femoral drill channel was located with a high degree of accuracy and reproducibility in the centre of the femoral footprint of the PLT (on average 1.1 (±1.6) mm distal from the centre). On the tibial side, the drill channel was in the distal third of the sulcus popliteus in all cases. On average, the channel was placed exactly at the level of the tip of the fibula (±1.5 mm) and 0.6 (±1.7) mm medially from the medial edge of the fibula. The centre of the channel was 13.4 (±2.3) mm distal from the joint line. Conclusions: The presented arthroscopic technique for PLT reconstruction is standardized, reproducible and has a high accuracy for the placement of the tibial and femoral tunnel. The technique could be clinically relevant for future arthroscopic posterolateral corner reconstructions. Level of evidence: III. © 2014, Springer-Verlag Berlin Heidelberg.


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.

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