[Periprosthetic joint infections : Latest developments, strategies and treatment algorithms]. / Periprothetische Früh- und Spätinfektionen : Neuste Entwicklungen, Strategien und Behandlungsalgorithmen.

BACKGROUND: Due to their multidimensional consequences, periprosthetic joint infections are a serious complication in arthroplasty. There are disagreements in the literature regarding their classification. At the same time, a consequence for the practical procedure cannot always be derived. THERAPEUTIC PROCEDURES: In addition to debridement with antibiotics and implant retention, there are options for a one or two-stage change in the therapeutic procedure. Although the preservation of implants is only possible in the case of acute infections with a short duration of symptoms, prosthesis changes are indicated with a longer symptom duration. For both procedures, there are interinstitutional deviating indication criteria, weighing pros and cons. Both have specific problems, such as, in particular, the duration of the antibiotics course, the question of anchoring the prosthesis and, in the case of a two-stage procedure, the shape of the spacer.

[Specific intraoperative and secondary complications of biological reconstructions following extralesional tumour resections of malignant bone tumours]. / Operationstypische und sekundäre Komplikationen biologischer Rekonstruktionsverfahren nach extraläsionaler Tumorresektion bei malignen Knochentumoren.

BACKGROUND: The treatment of primary malignant bone tumours is interdisciplinary and individually adapted to the patient. Nowadays, limb salvage surgery is usually possible, and the subsequent reconstruction is carried out either by implantation of modular tumour megaprostheses or by biological reconstruction procedures. Special surgical and secondary complications have to be considered. OBJECTIVES: Indication and explanation of various biological reconstruction procedures and presentation of specific peri- and postoperative complications. MATERIALS AND METHODS: An adapted literature review and the contribution of our own therapy experiences and case studies for the presentation of biological reconstructions and their complication management was performed. RESULTS: In biological reconstructions, autografts, allografts or a combination of autografts and allografts are used. Stabilization is achieved with screw and plate osteosyntheses. The most common secondary complications are pseudarthrosis, interponate fracture, graft necrosis and secondary malpositions. CONCLUSION: In selected cases, particularly at the upper extremities and in dia- or metaphyseal tumour sites, biological reconstruction after extralesional tumor resection is the surgical therapy of choice. The rate of long-term revision interventions is significantly lower compared to modular tumour megaprostheses. Biological reconstructions and the treatment of specific complications have to be performed in specialized centres for musculoskeletal surgical oncology/tumor orthopedics.

Disc cell therapy with bone-marrow-derived autologous mesenchymal stromal cells in a large porcine disc degeneration model.

PURPOSE: Disc regeneration through matrix-assisted autologous mesenchymal stromal cell therapy seems promising against disc degeneration with convincing results in small animal models. Whether these positive results can be transferred to larger animal models or humans is unclear. METHODS: Fibrin matrix-assisted autologous bone-marrow-derived mesenchymal stromal cell therapy was compared to acellular fibrin matrix therapy in a porcine in vivo model. First, disc degeneration was induced by annular puncture and partial nucleotomy with a large 16G-needle, and 12 weeks later, disc therapy was performed in a second surgery with a thinner 26G needle. Seventy-two lumbar discs from 12 aged adult pigs were evaluated by histology, micro-CT, and gene expression analysis 13 and 24 weeks after nucleotomy and 1 and 12 weeks after treatment, respectively. RESULTS: Radiologic disc height was not significantly different in both treatment groups. In the semi-quantitative histologic degeneration score, significant disc degeneration was still evident 1 week after treatment both in the mesenchymal stromal cell group and in the acellular fibrin matrix group. 12 weeks after treatment, degeneration was, however, not further increased and mesenchymal-stromal-cell-treated discs showed significantly less disc degeneration in the annulus fibrosus (p = 0.02), whereas reduction in the nucleus pulposus did not reach statistical significance. Cell treatment compared to matrix alone found less Col1 gene expression as a marker for fibrosis and more expression of the trophic factor BMP2 in the nucleus pulposus, whereas the inflammation marker IL1ß was reduced in the annulus fibrosus. CONCLUSIONS: Disc treatment with fibrin matrix-assisted autologous mesenchymal stromal cells reduced degenerative findings compared to acellular fibrin matrix alone. Regenerative changes, however, were not significant for all parameters showing limitations in a large biomechanically demanding model with aged discs. These slides can be retrieved under Electronic Supplementary Material.

[Diagnostics and treatment of benign spinal tumors]. / Diagnostik und Therapie benigner Tumoren der Wirbelsäule.

Benign tumors of the spine are rare and may lead to unspecific back pain. The classification of the lesion is typically achieved with a combination of imaging techniques (MRI and CT scans) and, in some cases, a histological sampling to allow differentiation from malignant processes. Both open and interventional (CT guided) biopsies are possible, depending on the localization of the tumor. Treatment strategies are diverse, require an interdisciplinary approach, and include operative and interventional procedures. The following article gives an overview of the most important benign tumors of the spine, the typical features in imaging, and treatment strategies.

Loss of notochordal cell phenotype in 3D-cell cultures: implications for disc physiology and disc repair.

INTRODUCTION: Embryonic notochordal disc nucleus cells (NC) have been identified to protect disc tissue against disc degeneration but in human beings NC phenotype gets lost with aging and the pathophysiological mechanisms are poorly understood. NC may stimulate other cells via soluble factors, and NC-conditioned medium can be used to stimulate matrix production of other disc cells and mesenchymal stem cells and thus may be of special interest for biological disc repair. As this stimulatory effect is associated with the NC phenotype, we investigated how cell morphology and gene-expression of the NC phenotype changes with time in 3D-cell culture. MATERIALS AND METHODS: NC and inner annulus chondrocyte-like cells (CLC) from immature pigtails (freshly isolated cells/tissue, 3D-alginate beads, 3D-clusters) were cultured for up to 16 days under normoxia and hypoxia. Protein-expression was analysed by immunohistology and gene-expression analysis was carried out on freshly isolated cells and cultured cells. Cell morphology and proliferation were analysed by two-photon-laser-microscopy. RESULTS: Two-photon-laser-microscopy showed a homogenous and small CLC population in the inner annulus, which differed from the large vacuole-containing NC in the nucleus. Immunohistology found 93 % KRT8 positive cells in the nucleus and intracellular and pericellular Col2, IL6, and IL12 staining while CLC were KRT8 negative. Freshly isolated NC showed significantly higher KRT8 and CAIII but lower Col2 gene-expression than CLC. NC in 3D-cultures demonstrated significant size reduction and loss of vacuoles with culture time, all indicating a loss of the characteristic NC morphology. Hypoxia reduced the rate of decrease in NC size and vacuoles. Gene-expression of KRT8 and CAIII in NC fell significantly early in culture while Col2 did not decrease significantly within the culture period. In CLC, KRT8 and CAIII gene-expression was low and did not change noticeably in culture, whereas Col2 expression fell with time in culture. CONCLUSIONS: 3D-culture caused a rapid loss of NC phenotype towards a CLC phenotype with disappearance of vacuoles, reduced cell size, increased proliferation, and gene-expression changes. These findings may be related to NC nutritional demands and support the latest hypothesis of NC maturation into CLC opposing the idea that NC get lost in human discs by cell death or apoptosis to be replaced by CLC from the inner annulus.

Short-term follow-up of disc cell therapy in a porcine nucleotomy model with an albumin-hyaluronan hydrogel: in vivo and in vitro results of metabolic disc cell activity and implant distribution.

PURPOSE: Cell therapy would be favorably performed immediately after nucleotomy, to restore intervertebral disc functionality and to slow down disc degeneration. Promising results were reported from small animal models but remaining problems, especially in larger animals, include loss of vital cells due to annular damage at the injection site and detrimental intradiscal conditions. The aim of the present study was to optimize cell-based disc therapy using a new albumin-hyaluronan hydrogel together with bone marrow-derived mesenchymal stem cells in a large porcine disc model. METHODS: Luciferase cell labeling was evaluated to follow-up stem cells metabolically up to 7 days in 3D cell cultures mimicking the harsh disc environment with low oxygen and glucose concentrations. As a pilot in vivo study, the implant was injected into porcine discs after removal of ~10% of nucleus volume and animals were killed immediately after surgery (n = 6) and 3 days later (n = 6). 24 discs were analyzed. Implant persistence and cell activity (luciferase + WST assay) were observed simultaneously. RESULTS: In vitro cell culture with reduction of glucose (20, 5, 0.5, 0 mM) and oxygen (21, 5, 2%) significantly decreased metabolic cell activity and luciferase activity after 3 days, with no recovery and a further decrease after 7 days, establishing luciferase activity as a metabolic sensor. During 3 days of 3D culture with disc-like conditions, luciferase activity decreased to 8%. In vivo, initial implant volume shrank to 61% at day 3 with evidence for hydrogel compression. Luciferase activity in vivo at day 3 was 2% without referencing but 23% after referencing to in vitro cell adaptation, and 38% after additional consideration of detected implant volume loss. CONCLUSION: In vitro analysis up to 7 days established for the first time luciferase activity as a metabolic sensor for mesenchymal stem cells used in regenerative disc therapy. Under the present protocol, short-term in vivo analysis after 3 days suggests improved implant retainment inside the disc and persistence of metabolically active cells; however, further studies will have to prove long-term in vivo outcome.

In vivo serum titanium ion levels following modular neck total hip arthroplasty--10 year results in 67 patients.

The objective of the present cross-sectional study was to determine in vivo titanium ion levels following cementless total hip arthroplasty (THA) using a modular stem system with different shapes for femoral canal fit and multiple neck options. A consecutive series of 173 patients (190 hips) who underwent cementless modular neck THA and a ceramic on polyethylene bearing with a median follow-up of 9 (7-13) years was evaluated retrospectively. According to a standardized protocol, titanium ion measurements were performed on 67 patients using high-resolution inductively coupled plasma-mass spectrometry. Ion levels were compared to a control group comprising patients with non-modular titanium implants (n=11) and to individuals without implants (n=23). Modular neck THA did not result in elevated titanium ion levels compared to non-modular THA. Compared to individuals without implants, both modular THA and non-modular THA showed elevated titanium ion levels. Absolute titanium ion levels, however, were comparatively low for both implants. The data suggest that the present modular stem system does not result in elevated systemic titanium ion levels in the medium term when compared to non-modular stems. Further longitudinal studies are needed to evaluate the use of systemic titanium ion levels as an objective diagnostic tool to identify THA failure and to monitor patients following revision surgery.

[Standards of microbiological diagnostics of spondylodiscitis]. / Standards der mikrobiologische Diagnostik der Spondylodiszitis.

In most cases spondylodiscitis is due to a monomicrobial infection caused by hematogenous dissemination of Staphylococcus aureus. There are, however, many other possible pathogens causing spondylodiscitis and the pathogen responsible can only be identified in approximately 50% of cases. This leads to delayed diagnosis and therapy and an increased morbidity and mortality rate. Failures in planning and performing material recovery are often the reason. As pathogen-specific antimicrobial treatment according to the results of susceptibility testing is the main component of interdisciplinary therapy, all available methods for identification of the pathogen, such as blood cultures, intraoperative and computed tomography (CT) guided biopsies of inflammatory fluids and tissues as well as molecular biological methods should be performed to optimize antimicrobial therapy.

[Radiofrequency ablation in spinal osteoid osteoma. Options and limits]. / Radiofrequenzablation bei Osteoidosteomen der Wirbelsäule. Möglichkeiten und Grenzen.

Osteoid osteoma was first described by Jaffe in 1935 as a benign bone neoplasm mainly located in the diaphyseal areas of long bones: 10% are located in the spine, mainly in the lumbar and thoracic posterior elements. Therapy is required due to nocturnal pain independent of the physical load and responds especially well to anti-inflammatory drugs due to the excessive production of prostaglandins in the nidus. Diagnosis is confirmed by multi-slice computed tomography (CT), magnetic resonance imaging (MRI) and skeletal scintigraphy scans. In cases with typical symptoms and imaging, open biopsies are rarely needed. Although CT-guided radiofrequency ablation is accepted as the gold standard treatment option for osteoid osteoma in the extremities, this technique is limited in spinal applications due to the risk of thermal damage to adjacent neurovascular structures. Technical advances in the administration of radiofrequency ablation have, however, resulted in new and expanded indications in the spine so that the necessity for open surgical excision of spinal osteoid osteoma is becoming less.

Injection of a polymerized hyaluronic acid/collagen hydrogel matrix in an in vivo porcine disc degeneration model.

INTRODUCTION: Disc degeneration and re-herniation after nucleotomy procedures are common problems. Simultaneous application of hyaluronic acid (HA)-based matrix has been proposed to limit disc degeneration. This, however, is hampered by loss of the substituted matrix out of the disc. Hence, in situ polymerization of the injected matrix with ultraviolet light (UVL) directly used after injection may be useful. Therefore, this study evaluates a new HA/collagen hydrogel matrix with in situ polymerization after implantation in an established porcine nucleotomy model. MATERIALS AND METHODS: 12 mature minipigs were used. A total of 60 lumbar discs were analyzed. 36 discs underwent partial nucleotomy with a 16G biopsy needle. Of those, 24 discs received matrix (porcine nucleus pulposus collagenous scaffold component and chemically modified HA) which was in situ polymerized using UVL immediately after transplantation. 12 nucleotomized discs and 24 non-nucleotomized discs served as controls. After 24 weeks, animals were killed. X-rays, MRIs, histology, and gene expression analysis were done. RESULTS: Disc height was reduced equally after sole nucleotomy and nucleotomy with HA treatment and in MRIs signal intensity decreased. For both nucleotomy groups, the nucleus histo-degeneration score showed a significant increase compared to controls. In histology, HA treatment resulted in more scarring and inflammation in the annulus. Gene expression of catabolic MMPs was up-regulated, whereas IFN-gamma, IL-6, and IL-1b were unchanged. CONCLUSION: Although nucleotomy and administration of the implant material did not cause generalized inflammation of the disc, localized annular damage with annulus inflammation and scarring resulted in detrimental degenerative disc changes. As a result, therapeutic strategies should strongly focus on the prevention of annular damage or techniques for annular repair to remain disc integrity.

Methods to monitor distribution and metabolic activity of mesenchymal stem cells following in vivo injection into nucleotomized porcine intervertebral discs.

Intervertebral disc (IVD) degeneration involves a series of biochemical and morphological changes leading to loss of spinal stability and flexibility. Cell therapy is promising to reconstitute IVDs with new cells, however, sustained metabolic activity seems crucial for an active contribution to regeneration. The aim of the present study was to establish methods for separate follow up of persistence and activity of autologous porcine mesenchymal stem cells (pMSC) after implantation into IVDs of Goettingen minipigs in vivo in order to conclude about the potential of such an intervention strategy. For quantitative follow up, the transfer matrix was supplemented with Al(2)O(3) particles and pMSC which were retrovirally labeled with firefly luciferase (pMSC-Luc). Six mature Goettingen minipigs underwent matrix based cell transfer after partial nucleotomy of lumbar IVDs (n = 24). Day 0 and day 3 segments were analyzed for retained volume of Al(2)O(3) particles by micro-computed-tomography (muCT) and for cell activity by luciferase enzyme assessment. Three days after injection a reduction of Al(2)O(3) particles (P = 0.028) to about 9% and of pMSC-Luc activity to about 7% of initial values (P = 0.003) was detected, which suggests loss of 90% of the implant material under in vivo conditions without evidence for reduced pMSC-Luc metabolic activity (P = 0.887). In conclusion, separate follow up of implant material and cell activity was possible and unravels problems with in vivo implant persistence after annular puncture rather than quick loss of cell activity. Therefore, IVD-regeneration-strategies should increasingly focus on annulus reconstruction in order to reduce implant loss due to annular failure.