Identifying Disparities in the Management of Hip Fractures Within Europe: A Comparison of 3 Health-Care Systems.

INTRODUCTION: This study investigates the management of hip fractures in a German maximum care hospital and compares these data to evidence-based standard and practice in 180 hospitals participating in the UK National Hip Fracture Database (NHFD) and 16 hospitals participating in the Irish Hip Fracture Database (IHFD). This is the first study directly comparing the management of hip fractures between 3 separate health-care systems within Europe. METHODS: Electronic medical data were collected retrospectively describing the care pathway of elderly patients with a hip fracture admitted to a large trauma unit in the south of Germany "University Hospital Freiburg" (UHF). The audit evaluated demographics, postoperative outcome, and the adherence to the 6 "Blue Book" standards of care. These data were directly compared with the data from the UK NHFD and the IHFD acquired from 180 and 16 hospitals, respectively. RESULTS: At 36 hours, 95.8% of patients had received surgery in UHF, compared to 71.5% in the NHFD and 58% of patients in the IHFD. The rate of in-hospital mortality was 4.7% compared to 7.1% in the NHFD and 5% in the IHFD. The mean average acute length of stay was 13.4 days compared to 16.4 days in the NHFD and 20 days in the IHFD. Reoperation rates are 3.3% compared to 1% in the NHFD and 1.1% in the IHFD; 50.5% of patients were discharged on bone protection medication, compared to 47% in the IHFD and 79.3% in the UK NHFD. DISCUSSION: Despite uniformly acknowledged evidence-based treatment guidelines, the management of hip fractures remains heterogeneous within Europe. CONCLUSION: These data show that different areas of the hip fracture care pathway in Germany, England, and Ireland, respectively, show room for improvement in light of the growing socioeconomic burden these countries are expected to face.

Dural ectasia associated with Mounier-Kuhn syndrome: a novel association in the context of spinal stenosis.

We present the case of a patient undergoing lumbar spine decompression for stenosis with a history of Mounier-Kuhn syndrome. The patient presented with axial lumbar spine pain over 6 months with progressive radicular pain to the left L3 dermatome. MRI confirmed spinal stenosis at L3/4 level with associated dural ectasia. The patient had an uneventful spinal decompression with resolution of radicular symptoms and axial spine pain. Dural ectasia poses a significant risk when operating on the lumbosacral spine. Larger cerebrospinal fluid volumes and a capacious dural canal can result in anaesthetic and orthopaedic complications such as inadequate spinal anaesthesia, complicated epidural analgesia, intraoperative dural tears and difficult pedicle screw insertion due to narrow pedicles. This is the first case in the literature detailing the association between dural ectasia and Mounier-Kuhn syndrome. We recommend adequate spinal imaging in patients with Mounier-Kuhn syndrome to exclude dural ectasia prior to undergoing lumbosacral spinal procedures.

The Challenge in Using Mesenchymal Stromal Cells for Recellularization of Decellularized Cartilage.

Some decellularized musculoskeletal extracellular matrices (ECM)s derived from tissues such as bone, tendon and fibrocartilaginous meniscus have already been clinical use for tissue reconstruction. Repair of articular cartilage with its unique zonal ECM architecture and composition is still an unsolved problem, and the question is whether allogenic or xenogeneic decellularized cartilage ECM could serve as a biomimetic scaffold for this purpose.Hence, this survey outlines the present state of preparing decellularized cartilage ECM-derived scaffolds or composites for reconstruction of different cartilage types and of reseeding it particularly with mesenchymal stromal cells (MSCs).The preparation of natural decellularized cartilage ECM scaffolds hampers from the high density of the cartilage ECM and lacking interconnectivity of the rather small natural pores within it: the chondrocytes lacunae. Nevertheless, the reseeding of decellularized ECM scaffolds before implantation provided superior results compared with simply implanting cell-free constructs in several other tissues, but cartilage recellularization remains still challenging. Induced by cartilage ECM-derived scaffolds MSCs underwent chondrogenesis.Major problems to be addressed for the application of cell-free cartilage were discussed such as to maintain ECM structure, natural chemistry, biomechanics and to achieve a homogenous and stable cell recolonization, promote chondrogenic and prevent terminal differentiation (hypertrophy) and induce the deposition of a novel functional ECM. Some promising approaches were proposed including further processing of the decellularized ECM before recellularization of the ECM with MSCs, co-culturing of MSCs with chondrocytes and establishing bioreactor culture e.g. with mechanostimulation, flow perfusion pressure and lowered oxygen tension. Graphical Abstract Synopsis of tissue engineering approaches based on cartilage-derived ECM.

Correction to "Macroscopical, Histological, and In Vitro Characterization of Nonosteoarthritic Versus Osteoarthritic Hip Joint Cartilage".

[This corrects the article DOI: 10.4137/CMAMD.S29844.].

Macroscopical, Histological, and In Vitro Characterization of Nonosteoarthritic Versus Osteoarthritic Hip Joint Cartilage.

Osteoarthritis (OA) might affect chondrocyte culture characteristics and complement expression. Therefore, this study addressed the interrelation between macroscopical and microscopical structure, complement expression, and chondrocyte culture characteristics in non-OA and OA cartilage. Femoral head cartilage samples harvested from patients with femoral neck fractures (FNFs) and OA were analyzed for macroscopical alterations using an in-house scoring system, graded histologically (Mankin score), and immunolabeled for complement regulatory proteins (CRPs) and receptors. Morphology of monolayer cultured chondrocytes isolated from a subset of samples was assessed. The macroscopical score distinguished the FNF and OA cartilage samples and correlated significantly with the histological results. Chondrocyte phenotype from FNF or OA cartilage differed. Complement receptor C5aR, CRPs CD55 and CD59, and weakly receptor C3AR were detected in the investigated FNF and OA cartilage, except for CD46, which was detected in only two of the five investigated donors. The in-house score also allows inexperienced observers to distinguish non-OA and OA cartilage for experimental purposes.

Chondrogenesis of human bone marrow mesenchymal stromal cells in highly porous alginate-foams supplemented with chondroitin sulfate.

To overcome the limited intrinsic cartilage repair, autologous chondrocyte or bone-marrow-derived mesenchymal stromal cell (BM-MSC) was implanted into cartilage defects. For this purpose suitable biocompatible scaffolds are needed to provide cell retention, chondrogenesis and initial mechanical stability. The present study should indicate whether a recently developed highly porous alginate (Alg) foam scaffold supplemented with chondroitin sulfate (CS) allows the attachment, survival and chondrogenesis of BM-MSCs and articular chondrocytes. The foams were prepared using a freeze-drying method; some of them were supplemented with CS and subsequently characterized for porosity, biodegradation and mechanical profile. BM-MSCs were cultured for 1-2 weeks on the scaffold either under chondrogenic or maintenance conditions. Cell vitality assays, histology, glycosaminoglycan (sGAG) assay, and type II and I collagen immunolabelings were performed to monitor cell growth and extracellular matrix (ECM) synthesis in the scaffolds. Scaffolds had a high porosity ~93-95% with a mean pore sizes of 237±48 µm (Alg) and 197±61 µm (Alg/CS). Incorporation of CS increased mechanical strength of the foams providing gradually CS release over 7 days. Most of the cells survived in the scaffolds. BM-MSCs and articular chondrocytes formed rounded clusters within the scaffold pores. The BM-MSCs, irrespective of whether cultured under non/chondrogenic conditions and chondrocytes produced an ECM containing sGAGs, and types II and I collagen. Total collagen and sGAG contents were higher in differentiated BM-MSC cultures supplemented with CS than in CS-free foams after 14 days. The cell cluster formation induced by the scaffolds might stimulate chondrogenesis via initial intense cell-cell contacts.

The influence of IL-10 and TNFα on chondrogenesis of human mesenchymal stromal cells in three-dimensional cultures.

Chondrogenic differentiated mesenchymal stromal cells (MSCs) are a promising cell source for articular cartilage repair. This study was undertaken to determine the effectiveness of two three-dimensional (3D) culture systems for chondrogenic MSC differentiation in comparison to primary chondrocytes and to assess the effect of Interleukin (IL)-10 and Tumor Necrosis Factor (TNF)α on chondrogenesis by MSCs in 3D high-density (H-D) culture. MSCs were isolated from femur spongiosa, characterized using a set of typical markers and introduced in scaffold-free H-D cultures or non-woven polyglycolic acid (PGA) scaffolds for chondrogenic differentiation. H-D cultures were stimulated with recombinant IL-10, TNFα, TNFα + IL-10 or remained untreated. Gene and protein expression of type II collagen, aggrecan, sox9 and TNFα were examined. MSCs expressed typical cell surface markers and revealed multipotency. Chondrogenic differentiated cells expressed cartilage-specific markers in both culture systems but to a lower extent when compared with articular chondrocytes. Chondrogenesis was more pronounced in PGA compared with H-D culture. IL-10 and/or TNFα did not impair the chondrogenic differentiation of MSCs. Moreover, in most of the investigated samples, despite not reaching significance level, IL-10 had a stimulatory effect on the type II collagen, aggrecan and TNFα expression when compared with the respective controls.

Tenocyte activation and regulation of complement factors in response to in vitro cell injury.

Inferior tendon healing can lead to scarring and tendinopathy. The role of complement in tendon healing is still unclear. The aim of this study was to understand tenocytes response to mechanical injury and whether complement is regulated by injury. Tenocytes were injured using an optimized automated scratch assay model. Using a self-assembled plotter system, 50 parallel lines of injury were created in a 6 cm diameter tenocyte cell layer. Tenocytes mitotic activity and survival post injury was assessed using FDA/ethidiumbromide assay. Furthermore, this injury model was combined with stimulation of the tenocytes with the complement split fragment C3a. Gene expression of C3aR, C5aR (CD88), CD46, CD55, tumor necrosis factor (TNF)α, interleukin (IL)-1ß, matrix metalloproteinase (MMP)-1 was analyzed. Immunolabeling for C5aR and CD55 was performed. An enhanced mitotic activity and some dead cells were detected in the vicinity of the scratches. Gene expression of the C3aR was suppressed after 4 h but induced after 24 h post injury. C5aR was down-regulated at 24 h, CD46 and CD55 were induced at 24 h in response to injury and CD55 was also elevated at 4 h. MMP-1 was upregulated by injury but both proinflammatory cytokines remained mainly unaffected. Combination of injury with C3a stimulation led to an enhanced C3aR, CD55 and TNFα gene expression. According to the gene expression data, the protein expression of C5aR was reduced and that of CD55 induced. In summary, a specific response of complement regulation was found in mechanically injured tenocytes which may be involved in healing responses.