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author:("krause, R.")
1.  Enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing 
Bone & Joint Research  2016;5(3):95-100.
Venous thromboembolism (VTE) is a major potential complication following orthopaedic surgery. Subcutaneously administered enoxaparin has been used as the benchmark to reduce the incidence of VTE. However, concerns have been raised regarding the long-term administration of enoxaparin and its possible negative effects on bone healing and bone density with an increase of the risk of osteoporotic fractures. New oral anticoagulants such as rivaroxaban have recently been introduced, however, there is a lack of information regarding how these drugs affect bone metabolism and post-operative bone healing.
We measured the migration and proliferation capacity of mesenchymal stem cells (MSCs) under enoxaparin or rivaroxaban treatment for three consecutive weeks, and evaluated effects on MSC mRNA expression of markers for stress and osteogenic differentiation.
We demonstrate that enoxaparin, but not rivaroxaban, increases the migration potential of MSCs and increases their cell count in line with elevated mRNA expression of C-X-C chemokine receptor type 4 (CXCR4), tumor necrosis factor alpha (TNFα), and alpha-B-crystallin (CryaB). However, a decrease in early osteogenic markers (insulin-like growth factors 1 and 2 (IGF1, IGF2), bone morphogenetic protein2 (BMP2)) indicated inhibitory effects on MSC differentiation into osteoblasts caused by enoxaparin, but not by rivaroxaban.
Our findings may explain the adverse effects of enoxaparin treatment on bone healing. Rivaroxaban has no significant impact on MSC metabolism or capacity for osteogenic differentiation in vitro.
Cite this article: Dr H. Pilge. Enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing. Bone Joint Res 2016;5:95–100. DOI: 10.1302/2046-3758.53.2000595.
PMCID: PMC4852789  PMID: 26989119
rivaroxaban; enoxaparin; human mesenchymal stromal cells (MSCs); low-molecular-weight heparins (LMWH); bone healing
2.  Patient blood management in Europe 
Preoperative anaemia is common in patients undergoing orthopaedic and other major surgery. Anaemia is associated with increased risks of postoperative mortality and morbidity, infectious complications, prolonged hospitalization, and a greater likelihood of allogeneic red blood cell (RBC) transfusion. Evidence of the clinical and economic disadvantages of RBC transfusion in treating perioperative anaemia has prompted recommendations for its restriction and a growing interest in approaches that rely on patients' own (rather than donor) blood. These approaches are collectively termed ‘patient blood management’ (PBM). PBM involves the use of multidisciplinary, multimodal, individualized strategies to minimize RBC transfusion with the ultimate goal of improving patient outcomes. PBM relies on approaches (pillars) that detect and treat perioperative anaemia and reduce surgical blood loss and perioperative coagulopathy to harness and optimize physiological tolerance of anaemia. After the recent resolution 63.12 of the World Health Assembly, the implementation of PBM is encouraged in all WHO member states. This new standard of care is now established in some centres in the USA and Austria, in Western Australia, and nationally in the Netherlands. However, there is a pressing need for European healthcare providers to integrate PBM strategies into routine care for patients undergoing orthopaedic and other types of surgery in order to reduce the use of unnecessary transfusions and improve the quality of care. After reviewing current PBM practices in Europe, this article offers recommendations supporting its wider implementation, focusing on anaemia management, the first of the three pillars of PBM.
PMCID: PMC3374574  PMID: 22628393
anaemia; outcome; patient blood management; transfusion
4.  Surgical hip dislocation in symptomatic cam femoroacetabular impingement: what matters in early good results? 
In order to assess outcome and possible predictors of early good results, a prospective study on 22 patients who were treated with save surgical hip dislocation for symptomatic isolated cam-type femoroacetabular impingement (FAI) was performed. After a follow-up of 6 and 12 months, standard clinical and radiographic parameters were recorded. A statistically significant improvement of the clinical status according to the Harris hip score could be assessed at six months (p-value = 0.003) and 12 months (p-value = 0.001) post-surgery. By comparing standard clinical and radiographic preoperative parameters with various follow-up outcomes, we revealed no specific parameter with predictive value. These findings are important for centers that have just started to use this surgical technique and are still identifying their learning curve.
PMCID: PMC3352194  PMID: 21719395
hip; FAI; surgery; outcome; predictors
5.  Migration pattern of cementless press fit cups in the presence of stabilizing screws in total hip arthroplasty 
The aim of this study was to evaluate the initial acetabular implant stability and late acetabular implant migration in press fit cups combined with screw fixation of the acetabular component in order to answer the question whether screws are necessary for the fixation of the acetabular component in cementless primary total hip arthroplasty. One hundred and seven hips were available for follow-up after primary THA using a cementless, porous-coated acetabular component. A total of 631 standardized radiographs were analyzed digitally by the "single-film-x-ray-analysis" method (EBRA). One hundred 'and one (94.4%) acetabular components did not show significant migration of more than 1 mm. Six (5.6%) implants showed migration of more than 1 mm. Statistical analysis did not reveal preoperative patterns that would identify predictors for future migration. Our findings suggest that the use of screw fixation for cementless porous- coated acetabular components for primary THA does not prevent cup migration.
PMCID: PMC3352209  PMID: 21486725
cementless; acetabular; fixation; with screws; without screws; EBRA; Total Hip Arthroplasty
6.  Midterm results following revision surgery in clubfeet 
International Orthopaedics  2007;33(2):515-520.
Relapse rates of surgically treated clubfeet are about 25%. We reviewed 43 patients (57 feet) treated for relapsed clubfoot deformity between 1992 and 2001 in our department. The average age of the patients at the time of revision surgery was 5.1 years, the mean follow-up was 6.6 years. Surgical therapy was performed using an algorithm according to age groups. The mean Atar score at follow-up was 77 points, representing a good outcome. Out of 57 feet, 20 (35%) were rated excellent, 24 (42%) good, 5 (9%) fair, and 8 (14%) poor. The number of previous surgical interventions had no influence on the outcome. Using an age related surgical algorithm, good postoperative results could be achieved in most of our patients, thus improving their functional situation. This emphasises the usefulness of the proposed algorithm in the difficult situation of recurrent clubfoot, while thorough analysis of the underlying deformity remains essential.
PMCID: PMC2899066  PMID: 18094969
7.  Spinning around or stagnation - what do osteoblasts and chondroblasts really like? 
The influcence of cytomechanical forces in cellular migration, proliferation and differentation of mesenchymal stem cells (MSCs) is still poorly understood in detail.
Human MSCs were isolated and cultivated onto the surface of a 3 × 3 mm porcine collagen I/III carrier. After incubation, cell cultures were transfered to the different cutures systems: regular static tissue flasks (group I), spinner flasks (group II) and rotating wall vessels (group III). Following standard protocols cells were stimulated lineage specific towards the osteogenic and chondrogenic lines. To evaluate the effects of applied cytomechanical forces towards cellular differentiation distinct parameters were measured (morphology, antigen and antigen expression) after a total cultivation period of 21 days in vitro.
Depending on the cultivation technique we found significant differences in both gen and protein expression.
Cytomechanical forces with rotational components strongly influence the osteogenic and chondrogenic differentiation.
PMCID: PMC3351846  PMID: 20159670
mesenchymal stem cells; cytomechanical forces; differentiation; osteoblast; chondroblast
8.  Clinical outcome after transfixation of the epiphysis with Kirschner wires in unstable slipped capital femoral epiphysis 
International Orthopaedics  2006;30(5):342-347.
Treatment of slipped capital femoral epiphysis (SCFE) is still controversial. Agreement has not yet been reached on the appropriate time to perform surgery, the necessity of repositioning manoeuvres, the type of implants for stabilisation, or the need for prophylactic treatment of the contralateral side. In this retrospective study, we present 29 patients with unstable (acute and acute-on-chronic) SCFE treated by internal fixation of the epiphysis with three or four Kirschner wires both therapeutically on the affected side and prophylactically on the not (yet) affected side. After hardware removal and mean follow-up of 3.5 years, radiological and clinical examination of hip function was carried out. X-ray in two planes showed no incidence of any slip progression. Applying the score used by Heyman and Herndon, 18 results (62.1%) were classified as excellent, nine (31.1%) as good, one (3.4%) as fair, and one (3.4%) as poor. The rate of severe complications such as chondrolysis and avascular necrosis of the femoral head was low in our series (0% and 6.8%, respectively). This form of therapeutic management shows good clinical results with low complication rates. The slip can be efficiently stabilised, progression is reliably prevented, and remodelling of the joint gives the patient good overall hip function. We see no indication for emergency surgery.
PMCID: PMC3172781  PMID: 16622669
9.  Significance of Nano- and Microtopography for Cell-Surface Interactions in Orthopaedic Implants 
Cell-surface interactions play a crucial role for biomaterial application in orthopaedics. It is evident that not only the chemical composition of solid substances influence cellular adherence, migration, proliferation and differentiation but also the surface topography of a biomaterial. The progressive application of nanostructured surfaces in medicine has gained increasing interest to improve the cytocompatibility and osteointegration of orthopaedic implants. Therefore, the understanding of cell-surface interactions is of major interest for these substances. In this review, we elucidate the principle mechanisms of nano- and microscale cell-surface interactions in vitro for different cell types onto typical orthopaedic biomaterials such as titanium (Ti), cobalt-chrome-molybdenum (CoCrMo) alloys, stainless steel (SS), as well as synthetic polymers (UHMWPE, XLPE, PEEK, PLLA). In addition, effects of nano- and microscaled particles and their significance in orthopaedics were reviewed. The significance for the cytocompatibility of nanobiomaterials is discussed critically.
PMCID: PMC2233875  PMID: 18274618
10.  Saving Implants BMP-2 Application in Revision Total Hip Surgery 
Besides others, there are two major problems in total hip replacement surgery which result in implant failure. First there is aseptic loosening due to a lack of implant biocompatibility or micromovements and second periimplant wear debris induced osteolysis which limits the survival rate of an implant. Regarding to recent data there are only limited therapeutic strategies to heal these bony defects without arthroplasty revision surgery. Since the investigation and characterization of adult mesenchymal stem cells (MSCs) from bone marrow, a cell and tissue engineering based therapy might be a promising solution to heal endoprosthesis associated bony defects. Moreover the application of growth factors in bone reconstructive surgery is another treatment concept to promote local bone regeneration.
Patient and Methods:
We report about a 73-year old patient with a painful weight bearing and a large, wear debris induced pelvic osteolysis after total hip arthroplasty. To prevent from salvage surgical procedures and preserve bone, a healing attempted was performed by filling the critical bony defect zone with a BMP-2/MSC composit.
Clinical and radiological follow-ups showed a progressive bony healing of the critical size defect area without any complications. Fifteen months after application the patient is still pain free, has no limitations in daily life or sport activities.
The case embarks on a strategy of non-embryonic stem cell and growth factor application to heal bony defects at patients with total hip endoprosthesis.
PMCID: PMC3614591  PMID: 23674982
arthroplasty; BMP; bone defect; stem cells; total hip replacement

Results 1-10 (10)