Prof. Dr. Marcus Jäger

Orthopaedic and Trauma Department
University of Duisburg-Essen

Author IDs

  • Accurate determination of hip implant wear, cup anteversion and inclination through AI automated 2D-3D registration
    Klebingat, S. and Bien, T. and Hürtgen, J. and Grover, P. and Dreischarf, M. and Alkhateeb, S. and Jäger, M. and Rose, G.
    Journal of Orthopaedic Research (2023)
    view abstract10.1002/jor.25538
  • Femoral neck fractures [Schenkelhalsfrakturen]
    Jäger, M. and Portegys, E. and Busch, A. and Wegner, A.
    Orthopadie 52 (2023)
    view abstract10.1007/s00132-023-04364-8
  • Injuries in the First German Inline Skater Hockey League [Verletzungen in der 1. Inline-Skaterhockey-Bundesliga]
    Breves, F. and Wegner, A. and Jäger, M. and Mayer, C.
    Sportverletzung-Sportschaden 37 (2023)
    view abstract10.1055/a-2017-6166
  • Bioaktivierung von Scaffolds bei Osteonekrose [Bioactivation of scaffolds in osteonecrosis]
    Jäger, M. and Busch, A. and Sowislok, A.
    Orthopadie (Heidelberg, Germany) 51 (2022)
    view abstract10.1007/s00132-022-04303-z
  • Cup positioning and its effect on polyethylene wear of vitamin E- and non-vitamin E-supplemented liners in total hip arthroplasty: radiographic outcome at 5-year follow-up
    Baghdadi, J. and Alkhateeb, S. and Roth, A. and Jäger, M. and Busch, A. and Alkhateeb, S. and Landgraeber, S. and Serong, S. and Haversath, M. and vonWasen, A. and Windhagen, H. and Flörkemeier, T. and Budde, S. and Kubilay, J. and Noll, Y. and Delank, K. and Baghdadi, J. and Willburger, R. and Dücker, M. and Wilke, A. and Hütter, F. and Jäger, M. and VITAS-Group
    Archives of Orthopaedic and Trauma Surgery (2022)
    view abstract10.1007/s00402-022-04424-2
  • Influence of a Calcium Phosphate Coating (BONIT®) on the Proliferation and Differentiation Potential of Human Mesenchymal Stroma Cells in the Early Phase of Bone Healing
    Eggert, A. and Buhren, B.A. and Schrumpf, H. and Haversath, M. and Ruppert, M. and Jäger, M. and Krauspe, R. and Zilkens, C.
    Journal of Functional Biomaterials 13 (2022)
    view abstract10.3390/jfb13040176
  • Major surgical trauma impairs the function of natural killer cells but does not affect monocyte cytokine synthesis
    Müller-Heck, R.M. and Bösken, B. and Michiels, I. and Dudda, M. and Jäger, M. and Flohé, S.B.
    Life 12 (2022)
    Major traumatic and surgical injury increase the risk for infectious complications due to immune dysregulation. Upon stimulation with interleukin (IL) 12 by monocyte/macrophages, natural killer (NK) cells release interferon (IFN) γ that supports the elimination of the pathogen. In the present study, we investigated the impact of invasive spine surgery on the relationship between monocytes and NK cells upon exposure to Staphylococcus aureus. Mononuclear cells and serum were isolated from peripheral blood of patients before and up to 8 d after surgery and stimulated with inactivated S. aureus bacteria. NK cell and monocyte function were determined by flow cytometry. NK cells continuously lost their ability to produce IFN-γ during the first week after surgery independently from monocyte-derived IL-12 secretion. IFN-γ synthesis was minimal on day 8 and was associated with decreased expression of the IL-12 receptor and activation of transcription factors required for IFNG gene transcription. Addition of recombinant IL-12 could at least partially restore NK cell function. Pre-operative levels of growth/differentiation factor (GDF) 15 in the serum corre-lated with the extent of NK cell suppression and with hospitalization. Thus, NK cell suppression after major surgery might represent a therapeutic target to improve the immune defense against opportunistic infections. © 2021 by the authors. Li-censee MDPI, Basel, Switzerland.
    view abstract10.3390/life12010013
  • Metal Artefact Reduction Sequences (MARS) in Magnetic Resonance Imaging (MRI) after Total Hip Arthroplasty (THA): A non-invasive approach for preoperative differentiation between periprosthetic joint infection (PJI) and aseptic complications?
    Busch, A. and Jäger, M. and Beck, S. and Wegner, A. and Portegys, E. and Wassenaar, D. and Theysohn, J. and Haubold, J.
    BMC Musculoskeletal Disorders 23 (2022)
    view abstract10.1186/s12891-022-05560-x
  • Post-traumatic necrosis of the humeral head-Endoprosthesis or joint preservation [Posttraumatische Humeruskopfnekrose – Endoprothese oder Gelenkerhalt]
    Wegner, A. and Wassenaar, D. and Busch, A. and Stanjek, M. and Mayer, C. and Jäger, M.
    Orthopadie (Heidelberg, Germany) 51 (2022)
    view abstract10.1007/s00132-022-04307-9
  • The Implant Proteome—The Right Surgical Glue to Fix Titanium Implants In Situ
    Jäger, M. and Latosinska, A. and Herten, M. and Busch, A. and Grupp, T. and Sowislok, A.
    Journal of Functional Biomaterials 13 (2022)
    view abstract10.3390/jfb13020044
  • A bicentric approach evaluating the combination of a hemispheric cup with a novel ceramic head in total hip arthroplasty
    Busch, A. and Wassenaar, D. and Zinser, W. and Jäger, M.
    Orthopedic Reviews 13 (2021)
    Medical ceramics are frequently used biomaterials as a liner in total hip arthroplasty. Strong efforts have been made to improve material properties over the last decades. Alumina toughened zirconia ceramics seem to be promising alternatives to further reduce fracture rates and squeaking phenomena. To answer the question if alumina toughened zirconia ceramic liners in combination with a cementless, hemispheric cup are able to reduce squeaking phenomena and fracture rates, we initiated a bicentric, mid-term trial. Noise phenomena will be recorded using MONA Score (Melbourne Orthopaedic Noise Assessment). Functional outcome (Harris Hip Score, University of California-Los Angeles, Forgotten Joint Score, EQ-5D Score, Visual Analogue Scale) and radiographic parameters will serve as secondary parameters. The study has been set up for 5 years, with follow-ups after 6-14 weeks, 12, 24 and 60 months. © the Author(s), 2021.
    view abstract10.4081/or.2021.8794
  • A Retrospective Single-Center Study of 23 Patients to Compare Gait before and after Total Hip Arthroplasty Using the S-ROM Modular Hip System
    Bahr, J. and Rosental, D. and Classen, T. and Krebs, S. and Jäger, M.
    Medical Science Monitor 28 (2021)
    Background: This retrospective study used the Harris hip score (HHS) and range of motion (ROM) to compare gait before and after total hip arthroplasty using the modular S-ROM® hip prosthesis in 23 patients treated at a single center. Material/Methods: For this study, 23 patients with severe hip deformity, who were treated with a total hip replacement using the S-ROM® modular hip system by DePuy® in the period from 2003 until 2008, underwent a 3-dimensional gait analysis before and after surgery. Values were compared with a validated data set of healthy subjects. Gait analysis took place using 8 infrared cameras (50 Hz), 2 force platforms of Advanced Medical Technology, Inc. (AMTI)®, and the Vicon® 512 system. The HHS and ROM of the hip joint were determined preoperatively and postoperatively. The follow-up period was 16.7±15.2 months. Results: A healthy gait pattern is characterized by an even stride length of both legs in relation to body height and relative symmetry of certain gait phases. These characteristics are influenced by the range of motion of the hip joint and by pelvic tilt. Symmetry could be achieved postoperatively in the stance phase and in the single-leg stance phase. However, the gait phases could not normalize. HHS and ROM improved postoperatively. Conclusions: The findings from this retrospective study showed that ROM and HHS significantly improved following THA with the S-ROM® hip prosthesis, but that gait did not completely return to normal. © Med Sci Monit, 2021.
    view abstract10.12659/MSM.934558
  • Bone Substitutes in Orthopaedic Surgery: Current Status and Future Perspectives
    Busch, A. and Wegner, A. and Haversath, M. and Jäger, M.
    Zeitschrift fur Orthopadie und Unfallchirurgie 159 (2021)
    Bone replacement materials have been successfully supplied for a long time. But there are cases, especially in critical sized bone defects, in which the therapy is not sufficient. Nowadays, there are multiple bone substitutes available. Autologous bone grafts remain the gold standard in bone regeneration. Yet, donor-site morbidity and the available amount of sufficient material are limitations for autologous bone grafting. This study aimed to provide information about the current status in research regarding bone substitutes. We report on the advantages and drawbacks of several bone substitutes. At the end, we discuss the current developments of combining ceramic substitutes with osteoinductive substances. © 2020. Thieme. All rights reserved.
    view abstract10.1055/a-1073-8473
  • Does needle design affect the regenerative potential of bone marrow aspirate? An in vitro study
    Feddahi, N. and Herten, M. and Tassemeier, T. and Rekasi, H. and Hackel, A. and Haversath, M. and Jäger, M.
    Life 11 (2021)
    While autologous bone is still the gold standard for treatment of bone defects, its availability is limited. Sufficient numbers of mesenchymal stroma cells (MSC) may be an alternative. Small volumes of bone marrow aspirate (BMA) were harvested with two different needle systems comparing the yield and regenerative potency of the MSCs. BMA (10 mL) was aspirated from the posterior iliac crest of 12 patients with degenerative spinal disc disease using both needle systems in each patient: the Jamshidi needle (JAM) and on the contralateral side the Marrow Cellution® Needle (AMC). Number of mononuclear cells (MNCs) and regeneration capacity (colony-forming unit/CFU) were determined. MSCs were characterized for surface markers and their differentiation into trilineages. There was no significant difference between the two harvesting needles regarding the quantity of MNCs in BMA: 5.2 ± 1.8 × 109 MNC/mL for AMC vs. 4.8 ± 2.5 × 109 MNC/mL for JAM, p = 0.182. The quantity of CFUs per ml BMA was similar for both groups: 3717 ± 5556 for AMC and 4305 ± 5507 for JAM (p = 0.695). The potency of MSCs expressed as colony-forming potential per 106 MNC resulted in 0.98 ± 1.51 for AMC and 1.00 ± 0.96 for JAM (p = 0.666). Regardless of the needle design, 10 mL bone marrow aspirate contains a sufficient number of about 40,000 MSCs that can be used to enhance bone healing. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
    view abstract10.3390/life11080748
  • Functionalization of synthetic bone substitutes
    Busch, A. and Jäger, M. and Mayer, C. and Sowislok, A.
    International Journal of Molecular Sciences 22 (2021)
    Bone substitutes have been applied to treat osseous defects for a long time. To prevent implant related infection (IRI) and enhance bone healing functionalized biomaterials, antibiotics and osteoinductive substances have been introduced. This study gives an overview of the current available surface-coated bone substitutes and provides an outlook for future perspectives. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
    view abstract10.3390/ijms22094412
  • Long-Term Radiographic Changes in Stemless Press-Fit Total Shoulder Arthroplasty
    Beck, S. and Patsalis, T. and Busch, A. and Dittrich, F. and Wegner, A. and Landgraeber, S. and Jäger, M.
    Zeitschrift fur Orthopadie und Unfallchirurgie 159 (2021)
    Introduction Stemmed humeral implants have represented the gold standard in total shoulder arthroplasty (TSA) for decades. Like many other joints, the latest trends in TSA designs aim at bone preservation. Current studies have demonstrated that native proximal humeral bone stresses are most closely mimicked by stemless implants. Nevertheless, there are concerns about the long-term performance of stemless designs. The aim of the present study was to evaluate the long-term radiographic changes at the proximal humerus in anatomical stemless press-fit TSA. Materials and Methods Between 2008 and 2010, 48 shoulders in 43 patients were resurfaced using an anatomic stemless shoulder prosthesis (TESS, Biomet). Thirty shoulders in twenty-five patients who were aged 65.7 ± 9.9 (34 to 82) years were available for clinical and radiographic review at a mean follow-up of 94.0 ± 8.9 (78 to 110) months. Results Radiographic changes of the proximal humerus due to stress shielding were found in 38.4% of the stemless TESS implants. Mild stress shielding accounted for 80% of the observed radiographic changes. Radiographs exhibited stable fixation of the stemless humeral press-fit implant at early and late follow-up. In contrast, radiolucent lines at the glenoid implant were found in 96.1% of the cases. Irrespective of the degree of radiographic changes, clinical scores (VAS, Quick-DASH, Constant score) significantly improved at follow-up. Conclusions The anatomic stemless press-fit implant seems to be favorable in terms of implant-related stress shielding. Clinical outcome was not affected by radiographic changes, demonstrating an 8-year clinical performance that seems to be comparable to conventional stemmed TSA. © 2020. Thieme. All rights reserved.
    view abstract10.1055/a-1079-6549
  • Osteonecrosis [Osteonekrosen]
    Jäger, M.
    Orthopade 50 (2021)
    view abstract10.1007/s00132-021-04147-z
  • Shoulder arthroplasty [Schulterendoprothetik]
    Wassenaar, D. and Busch, A. and Wegner, A. and Jäger, M.
    Orthopade 50 (2021)
    Arthroplasty of the shoulder joint leads to excellent clinical results if the indications are valid and the implantation is technically correct. Taking anatomical requirements and mechanical functions as well as material properties and developments in surgical techniques into account, articulations and anchoring systems have been developed which, as modular systems enable successful restoration of the biomechanics and consider the importance of the surrounding soft tissues. Scientific data show promising medium-term and long-term results in terms of functionality and pain reduction. Nevertheless, due to the limited bone stock for implant anchoring, especially loosening of the prosthesis or instability of the glenoid joint component, revision arthroplasty remains challenging. This review article summarizes the relevant aspects of shoulder arthroplasty. © 2021, Springer Medizin Verlag GmbH, ein Teil von Springer Nature.
    view abstract10.1007/s00132-020-04065-6
  • Synovial alpha-defensin at reimplantation in two-stage revision arthroplasty to rule out persistent infection
    Bielefeld, C. and Engler, H. and Jäger, M. and Wegner, A. and Wassenaar, D. and Busch, A.
    In Vivo 35 (2021)
    Background/Aim: Owing to the lack of a diagnostic gold standard, ruling out persistent periprosthetic joint infection (PJI) before second-stage surgery in the setting of two-stage revision arthroplasty constitutes a major challenge. We evaluated if the alpha-defensin-1 (AD-1) test could predict successful infection eradication before reimplantation of a new prosthesis. Patients and Methods: Our prospective study included 20 patients who underwent two-stage revision arthroplasty for treatment of PJI. A standard quantitative enzyme AD-1 immunoassay of synovial fluid, the synovial leukocyte esterase test and routine laboratory blood testing were performed prior to explantation and reimplantation. Treatment failure was defined according to the Delphi-based consensus criteria after a minimum follow-up of 1 year. Results: A 15% of our patients met the Delphi Criteria within 1 year. None of the markers investigated were significantly different in patients with and without reinfection. Conclusion: Further research is necessary to identify biomarkers more suitable for indicating persistent infection before reimplantation. © 2021 International Institute of Anticancer Research. All rights reserved.
    view abstract10.21873/INVIVO.12352
  • A novel multiple-cue observational clinical scale for functional evaluation of gait after stroke - The stroke mobility score (SMS)
    Raab, D. and Diószeghy-Léránt, B. and Wünnemann, M. and Zumfelde, C. and Cramer, E. and Rühlemann, A. and Wagener, J. and Gegenbauer, S. and Flores, F.G. and Jäger, M. and Zietz, D. and Hefter, H. and Kecskeméthy, A. and Siebler, M.
    Medical Science Monitor 26 (2020)
    Background: For future development of machine learning tools for gait impairment assessment after stroke, simple observational whole-body clinical scales are required. Current observational scales regard either only leg movement or discrete overall parameters, neglecting dysfunctions in the trunk and arms. The purpose of this study was to introduce a new multiple-cue observational scale, called the stroke mobility score (SMS). Material/Methods: In a group of 131 patients, we developed a 1-page manual involving 6 subscores by Delphi method using the video-based SMS: trunk posture, leg movement of the most affected side, arm movement of the most affected side, walking speed, gait fluency and stability/risk of falling. Six medical raters then validated the SMS on a sample of 60 additional stroke patients. Conventional scales (NIHSS, Timed-Up-And-Go-Test, 10-Meter-Walk-Test, Berg Balance Scale, FIM-Item L, Barthel Index) were also applied. Results: (1) High consistency and excellent inter-rater reliability of the SMS were verified (Cronbach's alpha >0.9). (2) The SMS subscores are non-redundant and reveal much more nuanced whole-body dysfunction details than conventional scores, although evident correlations as e.g. between 10-Meter-Walk-Test and subscore “gait speed” are verified. (3) The analysis of cross-correlations between SMS subscores unveils new functional interrelationships for stroke profiling. Conclusions: The SMS proves to be an easy-to-use, tele-applicable, robust, consistent, reliable, and nuanced functional scale of gait impairments after stroke. Due to its sensitivity to whole-body motion criteria, it is ideally suited for machine learning algorithms and for development of new therapy strategies based on instrumented gait analysis. © Med Sci Monit
    view abstract10.12659/MSM.923147
  • A possible mobile health solution in orthopedics and trauma surgery: Development protocol and user evaluation of the ankle joint app
    Dittrich, F. and Back, D.A. and Harren, A.K. and Jäger, M. and Landgraeber, S. and Reinecke, F. and Beck, S.
    JMIR mHealth and uHealth 8 (2020)
    Background: Ankle sprains are one of the most frequent sports injuries. With respect to the high prevalence of ankle ligament injuries and patients' young age, optimizing treatment and rehabilitation is mandatory to prevent future complications such as chronic ankle instability or osteoarthritis. Objective: In modern times, an increasing amount of smartphone usage in patient care is evident. Studies investigating mobile health (mHealth)-based rehabilitation programs after ankle sprains are rare. The aim of this study was to expose any issues present in the development process of a medical app as well as associated risks and chances. Methods: The development process of the Ankle Joint App was defined in chronological order using a protocol. The app's quality was evaluated using the (user) German Mobile App Rating Scale (MARS-G) by voluntary foot and ankle surgeons (n=20) and voluntary athletes (n=20). Results: A multidisciplinary development team built a hybrid app with a corresponding backend structure. The app's content provides actual medical literature, training videos, and a log function. Excellent interrater reliability (interrater reliability=0.92; 95% CI 0.86-0.96) was obtained. The mean overall score for the Ankle Joint App was 4.4 (SD 0.5). The mean subjective quality scores were 3.6 (surgeons: SD 0.7) and 3.8 (athletes: SD 0.5). Behavioral change had mean scores of 4.1 (surgeons: SD 0.7) and 4.3 (athletes: SD 0.7). The medical gain value, rated by the surgeons only, was 3.9 (SD 0.6). Conclusions: The data obtained demonstrate that mHealth-based rehabilitation programs might be a useful tool for patient education and collection of personal data. The achieved (user) MARS-G scores support a high quality of the tested app. Medical app development with an a priori defined target group and a precisely intended purpose, in a multidisciplinary team, is highly promising. Follow-up studies are required to obtain funded evidence for the ankle joints app's effects on economical and medical aspects in comparison with established nondigital therapy paths. © 2020 JMIR Publications. All rights reserved.
    view abstract10.2196/16403
  • Ceramic scaffolds in a vacuum suction handle for intraoperative stromal cell enrichment
    Busch, A. and Herten, M. and Haversath, M. and Kaiser, C. and Brandau, S. and Jäger, M.
    International Journal of Molecular Sciences 21 (2020)
    During total joint replacement, high concentrations of mesenchymal stromal cells (MSCs) are released at the implantation site. They can be found in cell–tissue composites (CTC) that are regularly removed by surgical suction. A surgical vacuum suction handle was filled with bone substitute granules, acting as a filter allowing us to harvest CTC. The purpose of this study was to investigate the osteopromotive potential of CTC trapped in the bone substitute filter material during surgical suction. In the course of 10 elective total hip and knee replacement surgeries, β-tricalcium-phosphate (TCP) and cancellous allograft (Allo) were enriched with CTC by vacuum suction. Mononuclear cells (MNC) were isolated from the CTC and investigated towards cell proliferation and colony forming unit (CFU) formation. Furthermore, MSC surface markers, trilineage differentiation potential and the presence of defined cytokines were examined. Comparable amounts of MNC and CFUs were detected in both CTCs and characterized as MSC ‰ of MNC with 9.8 ± 10.7‰ for the TCP and 12.8 ± 10.2‰ for the Allo (p = 0.550). CTCs in both filter materials contain cytokines for stimulation of cell proliferation and differentiation (EGF, PDGF-AA, angiogenin, osteopontin). CTC trapped in synthetic (TCP) and natural (Allo) bone substitute filters during surgical suction in the course of a joint replacement procedure include relevant numbers of MSCs and cytokines qualified for bone regeneration. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
    view abstract10.3390/ijms21176393
  • Diagnostic Accuracy of Synovial Neopterin, TNF-α and Presepsin in Periprosthetic Joint Infection: A Prospective Study
    Busch, A. and Jäger, M. and Engler, H. and Wasssenaar, D. and Bielefeld, C. and Wegner, A.
    Zeitschrift fur Orthopadie und Unfallchirurgie (2020)
    Background Due to the lack of specificity of conventional diagnostic tools, the prediction of periprosthetic joint infections (PJI) remains challenging. The purpose of this study was to evaluate the accuracy of synovial fluid neopterin, presepsin, and TNF-α as diagnostic parameters and to compare it to the biomarkers recommended in the 2018 definition of periprosthetic hip and knee infection. Methods Between August 2018 and July 2019, a prospective cohort study was conducted in 80 patients with painful hip, shoulder, and knee arthroplasty. In addition to medical history, clinical and laboratory data were gathered. PJI was diagnosed based on the 2018 definition of periprosthetic hip and knee infection. Synovial joint fluid was analyzed for biomarker measurement using standard quantitative enzyme immunoassay kits. Results Fifty-three patients (66%) were classified as the aseptic group and twenty-seven patients (34%) as the PJI group. The mean levels of synovial fluid neopterin were significantly higher (p < 0.01) in the PJI group than those in the aseptic group (aseptic 8.3 ± 6.9 vs. PJI 20.9 ± 21.4 nmol/L). The average values of synovial fluid TNF-α and presepsin were not significantly higher in the PJI group than those in the aseptic group (presepsin: Aseptic 0.13 ± 0.19 vs. PJI 0.11 ± 0.32 ng/mL, p = 0.08; TNF-α: Aseptic 6.6 ± 7.3 vs. PJI 46.3 ± 123.2 pg/mL, p = 0.17). Synovial fluid neopterin was 59% specific and 74% sensitive with a cut-off value of 7.2 nmol/L. The sensitivity and specificity of synovial fluid TNF-α were 63 and 51% with a cut-off value of 3.9 pg/mL. Synovial fluid presepsin was 51% specific and 29% sensitive with a cut-off value above 0.06 ng/mL. Conclusion Synovial fluid neopterin appears to a reliable diagnostic marker for detection of PJI. In contrast, synovial fluid TNF-α and presepsin are not suitable to exclude or diagnose PJI. © 2020 Cambridge University Press. All rights reserved.
    view abstract10.1055/a-1303-5105
  • Equivalent Mid-Term Results of Open vs Endoscopic Gluteal Tendon Tear Repair Using Suture Anchors in Forty-Five Patients
    Maslaris, A. and Vail, T.P. and Zhang, A.L. and Patel, R. and Jäger, M. and Bini, S.A.
    Journal of Arthroplasty 35 (2020)
    Background: Little is known about the relative efficacy of open (OGR) vs endoscopic (EGR) gluteal tendon repair of gluteal tendon tears in minimizing pain and restoring function. Our aim is to compare these 2 surgical techniques and quantify their impact on clinical outcomes. Methods: All patients undergoing gluteal tendon tear repair at our institution between 2015 and 2018 were retrospectively reviewed. Pain scores, limp, hip abduction strength, and the use of analgesics were recorded preoperatively and at last follow-up. The Hip disability and Osteoarthritis Outcome Score Junior and Harris Hip Score Section1 were obtained at last follow-up. Fatty degeneration was quantified using the Goutallier-Fuchs Classification (GFC). Statistical analysis was conducted using one-way analysis of variance and t-tests. Results: Forty-five patients (mean age 66, 87% females) met inclusion criteria. Average follow-up was 20.3 months. None of the 10 patients (22%) undergoing EGR had prior surgery. Of 35 patients (78%) undergoing OGR, 12 (27%) had prior hip replacement (75% via lateral approach). The OGRs had more patients with GFC ≥2 (50% vs 11%, P = .02) and used more anchors (P = .03). Both groups showed statistical improvement (P ≤ .01) for all outcomes measured. GFC >2 was independently associated with a worst limp and Harris Hip Score Section 1 score (P = .05). EGR had a statistically higher opioid use reduction (P < .05) than OGR. Other comparisons between EGR and OGR did not reach statistical significance. Conclusion: In this series, open vs endoscopic operative approach did not impact clinical outcomes. More complex tears were treated open and with more anchors. Fatty degeneration adversely impacted outcomes. Although further evaluation of the efficacy of EGR in complex tears is indicated, both approaches can be used successfully. © 2020 Elsevier Inc.
    view abstract10.1016/j.arth.2020.03.013
  • Evaluation of intra- and interobserver reliability in the assessment of the ‘critical trochanter angle’
    Serong, S. and Schutzbach, M. and Zovko, I. and Jäger, M. and Landgraeber, S. and Haversath, M.
    European Journal of Medical Research 25 (2020)
    Background: The recently described ‘critical trochanter angle’ (CTA) is a novel parameter in the preoperative risk assessment of stem malalignment in total hip arthroplasty. As its reproducibility needs to be evaluated, the given study aims to investigate intra- and interobserver reliability. It is hypothesized that both analyses justify the clinical use of the CTA. Methods: A total of 100 pelvic radiographs obtained prior to total hip arthroplasty were retrospectively reviewed by four observers with different levels of clinical experience. The CTA was measured twice by each observer at different occasions in the previously described technique. Intra- and interobserver reliability was evaluated using intraclass correlation coefficients (ICC) with confidence intervals (CI) and the Bland–Altman approach. Results: The mean CTA in both measuring sequences was 20.58° and 20.78°. The observers’ means ranged from 17.76° to 25.23°. Intraobserver reliability showed a mean difference of less than 0.5° for all four observers (95% limit of agreement: − 7.70–6.70). Intraobserver ICCs ranged from 0.92 to 0.99 (CI 0.88–0.99). For interobserver variation analysis, ICCs of 0.83 (CI 0.67–0.90) and 0.85 (CI 0.68–0.92) were calculated. Conclusion: Analyses concerning intra- and interobserver reliability in the assessment of the CTA showed ‘very good’ and ‘good’ results, respectively. In view of these findings, the use of the CTA as an additional preoperative parameter to assess the risk of intraoperative stem malalignment seems to be justified. © 2020, The Author(s).
    view abstract10.1186/s40001-020-00469-4
  • First ray alignment in Lapidus arthrodesis – Effect on plantar pressure distribution and the occurrence of metatarsalgia
    Busch, A. and Wegner, A. and Haversath, M. and Brandenburger, D. and Jäger, M. and Beck, S.
    Foot 45 (2020)
    Background: Lapidus arthrodesis is an established treatment option for severe hallux valgus deformity especially in patients suffering from instability of the first tarsometatarsal joint. Surgery related metatarsalgia is known to be associated with persistent elevation of the first ray after realignment surgery. Nevertheless, detailed information on ideal positioning of the first ray in Lapidus surgery is missing so far. This study was designed to determine any correlations between radiographic and pedobarographic outcome following the Lapidus procedure with regard to clinical outcome and the occurrence of metatarsalgia. Methods: Thirty feet (28 patients) after Lapidus surgery were available for follow-up at 42.5 ± 21.0 months. All subjects had radiographic and pedobarographic evaluation of the operated foot and patient satisfaction was recorded using questionnaires. Results: Metatarsalgia was associated with a poorer outcome in FADI and AOFAS scores (p < 0.005). A lateral shift of plantar pressure distribution to the third metatarsal head in these cases could be observed. Although Lapidus surgery resulted in significant shortening of the first metatarsal, no correlation to the occurrence of metatarsalgia was detectable. Likewise, axial plane malalignment showed no influence, whereas elevation of the first ray was highly correlated to surgery related metatarsalgia (p = 0.007). Subjects suffering from metatarsalgia had a higher BMI (body mass index), but its effect on metatarsalgia turned out not to be significant (p = 0.090). Conclusion: In Lapidus surgery realignment of the first metatarsal in the sagittal plane seems to be decisive for good clinical outcome. Failing to plantarflex the arthrodesis resulted in a lateral shift of plantar loading with overload of the lesser metatarsals and the occurrence of metatarsalgia. © 2020
    view abstract10.1016/j.foot.2020.101686
  • Functional Knee Performance Differences in Handball are Depending on Playing Class
    Rühlemann, A. and Mayer, C. and Haversath, M. and Jäger, M.
    International Journal of Sports Medicine 41 (2020)
    Handball is one of the most traumatic sports. The knee is the most commonly injured joint. To prevent knee injuries, optimal functional knee stability is of great importance. Nevertheless, there is still no consensus about objective criteria for knee function. Depending on playing class, injury rates seem to differ. The purpose of this study was to evaluate knee function in handball depending on playing class and to establish reference data for functional knee stability. 261 handball players (25.1±5.8 years) performed a functional test including two-A nd one-legged stability assessments, jump tests, speed and agility analysis. Except for balance, differences between playing classes were detected in all tests with superior performance of high-class players (Germany's 1st (Oberliga) and 2nd (Verbandsliga) non-elite playing class). High-class players achieved significant better results in jumping height (p≤0.011-0.029), relative power per body weight in the two-legged counter movement jump (p≤0.023) and speed and agility tests (p≤0.001). This study illustrates the relevance of playing class specific screening. Sports and playing class-specific databases will help to identify individual deficits and strengths in order to prevent injury and increase performance. Moreover, objective criteria for return to sports can be established. © 2020 EDP Sciences. All rights reserved.
    view abstract10.1055/a-1121-7635
  • Functional knee stability in non-elite handball: balance and jump performance differ based on players’ position
    Rühlemann, A. and Mayer, C. and Albrecht, T. and Jäger, M.
    Knee Surgery, Sports Traumatology, Arthroscopy 28 (2020)
    Purpose: Despite the great evolvement of sports medicine, there is still a lack of consensus among sports physicians regarding the decision of return to sports after knee injury, especially in non-elite sports. Currently, no sport-specific reference data for an objective reliable evaluation of functional knee stability exist. The purpose of this study was to assess objective measures on knee joint stability from an established test battery in non-elite handball. It was assumed that players’ knee stability differs depending on their field position. Methods: One-hundred and sixty-five non-elite handball players with a mean age of 24.3 ± 5.5 years underwent a test battery including two-legged and one-legged stability tests, two-legged and one-legged counter movement jumps, two-legged plyometric jumps, one-legged speedy jumps, and a quick feed test. Results: Athletes’ physical performance differs in terms of field position. Significant differences between handball players of different positions were found in regard to two-legged stability (p < 0.036) and one-legged stability in the dominant leg (p < 0.009). Players of different positions differed in ground contact time of the plyometric jumps (p < 0.017), whereas the other functional tests did not show significant differences. Conclusion: This study is first to report differences in functional knee stability of non-elite handball players on the basis of objective data. Significant differences of functional performance were noted, which were in congruence with position-specific demands. These findings demonstrate the importance of position-specific screening and training to prevent injuries. Level of evidence: II. © 2019, European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).
    view abstract10.1007/s00167-019-05693-y
  • Injuries and Overuse Syndromes in Rink Hockey Players
    Husen, M. and Burgsmüller, L. and Burggraf, M. and Jager, M. and Dudda, M. and Kauther, M.
    International Journal of Sports Medicine (2020)
    Rink Hockey is a high-speed low-contact sport with a widely recognized injury potential. Played with a hard ball by players wearing little or no protective gear, the rates of concussions and head injuries are of high interest. In this study, we reviewed and investigated injuries sustained by 108 German National League rink hockey players. We conducted an epidemiological cross-sectional study to determine sport-specific injuries and injury patterns in female and male rink hockey players. Data were collected by a standardized questionnaire. A total of 108 players participated in the study. The combined rate of injuries were 9.4/1000 athlete exposures. There was no significant difference between injury rates during games and practice. A sex-specific difference was not detected. Head injuries were the most frequent type (20.8% of all injuries). Concussions made up 7% of all head injuries with a rate of 0.76/1000 athlete exposure. Ball contact was the cause for 31% of injuries, while player contact generated 26.2% of all injuries. High rates of ball-contact-related injuries resulted in time loss and medical consultations. Head injuries were frequent, however did not result in significant time loss as compared to other injuries. The use of protective gear should be recommended. © 2020 Cambridge University Press. All rights reserved.
    view abstract10.1055/a-1212-0780
  • Is Procalcitonin (PCT) a reliable biomarker for preoperative diagnosing of low grade periprosthetic joint infection? A prospective study
    Busch, A. and Jäger, M. and Engler, H. and Haversath, M. and Bielefeld, C. and Landgraeber, S. and Wegner, A.
    BMC Musculoskeletal Disorders 21 (2020)
    Background: Since a "gold-standard" is missing, diagnosing periprosthetic joint infection (PJI) remains a challenge in orthopedic surgery. The purpose of this study was to evaluate the accuracy of serum and synovial fluid Procalcitonin (S-PCT and SF-PCT) as a diagnostic parameter and to compare it to the biomarkers recommended in the 2018 Definition of periprosthetic hip and knee infection. Methods: Between August 2018 and July 2019, a prospective cohort study was conducted in 70 patients with painful hip, shoulder and knee arthroplasty. Besides medical history, clinical and laboratory data was gathered. PJI was diagnosed based on the 2018 Definition of periprosthetic hip and knee infection. Preoperative blood and synovial joint fluid were taken for PCT measurement. S-PCT and SF-PCT levels were measured using standard quantitative PCT enzyme immunoassays. Results: Twenty three patients (33%) were classified as the PJI group and fourty seven patient (67%) as the aseptic group. The mean levels of S-PCT were significantly (p < 0.001) higher in the PJI group than those in the aseptic group (PJI 0.05 ± 0.21 ng/mL (0.0-1.03) vs. aseptic 0.02 ± 0.03 ng/mL (0.0-0.18)). In synovial fluid, the mean PCT values in the aseptic group were significantly higher (p < 0.001) than those of PJI group (PJI 2.7 ± 1.4 ng/mL (0.53-9.7) vs. aseptic 8.7 ± 2.5 ng/mL (0.25-87.9)). S- PCT, with a cut-off level of 0.5 ng/mL, had a sensitivity of 13.0% and a specificity of 91.0%. SF-PCT, with a cut-off level of 5.0 ng/mL, had a sensitivity of 13.0% and a specificity of 52.0%. Conclusion: S-PCT and SF-PCT appeared to be no reliable biomarkers in the differential diagnosis of PJI from aseptic loosening in total joint arthroplasty. © 2020 The Author(s).
    view abstract10.1186/s12891-020-03266-6
  • Modified advanced core decompression (mACD) [Modifizierte „advanced core decompression“ (mACD)]
    Landgraeber, S. and Jäger, M.
    Operative Orthopadie und Traumatologie 32 (2020)
    Objective: The modified advanced core decompression (mACD) combines the advantages of a low invasive core decompression with maximal removal of osteonecrotic bone and a biologic reconstruction of the resulting bone defect. Indications: Avascular (atraumatic) osteonecrosis of the femoral head (ARCO stage II). Contraindications: Subchondral fractures (ARCO stage III); advanced osteoarthritis (e.g., ACRO stage IV); persisting risk factors such as high-dose corticoid therapy, chemotherapy, alcohol abuse; open growth plates; history of side effects or intolerance to components of the applied bone substitute; lack of patient compliance; osteomyelitis or other septic conditions. Surgical technique: Supine positioning on the operation table, skin disinfection, and sterile draping. Skin incision and core decompression using a 3.2 mm guide wire. Removal of a bone cylinder from a nonaffected area of the femoral neck using a hollow trephine. Drilling of the osteonecrotic area over the applied wire up to 5 mm to the subchondral bone under fluoroscopy, insertion of an expandable bone knife and removal of the osteonecrotic bone supported by a curette. Bone grafting of the autologous bone into the subchondral defect zone and filling of the drill canal by resorbable bone substitute. Postoperative management: Bed rest for 24 h, then partial weight bearing (20 kg) on crutches for 2–6 weeks depending on the bone quality in the defect zone and the applied bone substitute. Results: Midterm superiority (2 years) in hip survival of the mACD over advanced core depression and core depression, especially in ARCO stage II. © 2020, Springer Medizin Verlag GmbH, ein Teil von Springer Nature.
    view abstract10.1007/s00064-020-00653-z
  • Multitask-learning for the extraction of avascular necrosis of the femoral head in MRI
    Pham, D.D. and Dovletov, G. and Serong, S. and Landgraeber, S. and Jäger, M. and Pauli, J.
    Informatik aktuell (2020)
    In this paper, we present a 2D deep multitask learning approach for the segmentation of small structures on the example of avascular necrosis of the femoral head (AVNFH) in MRI. It consists of one joint encoder and three separate decoder branches, each assigned to its own objective. We propose using a reconstruction task to initially pre-train the encoder and shift the objective towards a second necrosis segmentation task in a reconstruction-dependent loss adaptation manner. The third branch deals with the rough localization of the topographical neighborhood of possible femoral necrosis areas. Its output is used to emphasize the roughly approximated location of the segmentation branch’s output. The evaluation of the segmentation performance of our architecture on coronal T1-weighted MRI volumes shows promising improvements compared to a standard U-Net implementation. © Springer Fachmedien Wiesbaden GmbH, ein Teil von Springer Nature 2020.
    view abstract10.1007/978-3-658-29267-6_31
  • Pseudarthroses [Pseudarthrosen]
    Jäger, M. and Wassenaar, D. and Busch, A. and Haversath, M.
    Orthopade 49 (2020)
    Fractures and osteotomies are characterized by a structural discontinuity of the affected bone with formation of a gap. If bone healing does not lead to an osseous bridging of the fragments within a time period of 6 months a nonunion (pseudarthrosis) occurs. In this stage spontaneous bone healing is unlikely in the future without any intervention. Pseudarthrosis is classified into hypertrophic and atrophic types. Moreover, the differentiation between aseptic and septic conditions, the size of the defect, the local blood supply and the mechanical stability are crucial for treatment planning. The type of pseudarthrosis and the accompanying comorbidities can be classified in scoring systems and influence the selection of the treatment procedure. The operative principles aim at the vitalization of atrophic bone parts, achieving sufficient stabilization and cures the infection, whereas nonoperative measures are primarily supportive measures. The foundation of successful treatment is the minimization of individual risk profiles and sufficient patient compliance. © 2020, Springer Medizin Verlag GmbH, ein Teil von Springer Nature.
    view abstract10.1007/s00132-020-03920-w
  • Synovial bone sialoprotein indicates aseptic failure in total joint arthroplasty
    Busch, A. and Jäger, M. and Dittrich, F. and Wegner, A. and Landgraeber, S. and Haversath, M.
    Journal of Orthopaedic Surgery and Research 15 (2020)
    Background: Until today, a reliable diagnostic discrimination between periprosthetic joint infections (PJI) and aseptic failure (AF) after total joint arthroplasty (TJA) remains challenging. Nearly all recent research focused on synovial markers to be elevated in PJI rather than in AF patients. In this study, synovial bone sialoprotein (sBSP) was investigated in PJI and AF arthroplasty patients before revision surgery. Methods: sBSP and C-reactive protein (CRP) were determined in synovial fluid samples of PJI (n = 13) patients fulfilling the MSIS criteria and AF (n = 25) patients. Beside descriptive analysis and comparison, computed statistics determined the area under the receiver operating characteristics curve (AUC) to evaluate the discrimination ability of the tested synovial markers. Results: In patients with PJI according to the MSIS criteria, mean sBSP was significantly lower: 14.8 ng/ml (95% CI 5.5-24.1) vs. 38.2 ng/ml in the AF group (95% CI 31.1-45.3), p ≤ 0.001. Conversely, mean sCRP was significantly higher in PJI patients: 8.4 μg/ml (95% CI 0-17.2) vs. 1.8 μg/ml in the AF group (95% CI 0.9-2.8), p = 0.032. The AUC of sCRP in PJI patients was 0.71. The AUC of sBSP in AF revision arthroplasty patients was 0.83. The detection of osteolyses was not associated with higher sBSP concentrations. Conclusions: Considering the MSIS criteria, significantly higher sBSP concentrations were found in synovial fluid samples of AF compared to PJI patients. sCRP showed only fair, sBSP good discrimination potential. If it is not clear whether PJI is present or not, sBSP may be considered as an add-on synovial marker. © 2020 The Author(s).
    view abstract10.1186/s13018-020-01718-2
  • The direct anterior approach provokes varus stem alignment when using a collarless straight tapered stem
    Haversath, M. and Lichetzki, M. and Serong, S. and Busch, A. and Landgraeber, S. and Jäger, M. and Tassemeier, T.
    Archives of Orthopaedic and Trauma Surgery (2020)
    Introduction: Inaccurate stem implantation can cause unsatisfactory offset reconstruction and may result in insufficient gluteal muscle function or aseptic loosening. In this study, stem alignment of a collarless straight tapered HA-coated stem was retrospectively analyzed during the learning phase of the direct anterior approach (DAA) for primary total hip arthroplasty (THA). Material and methods: From Jan 2013 to Jun 2015, a total of 93 cementless THA were implanted in patients with unilateral coxarthrosis via the DAA in a two surgeon setting using the Corail® or Trendhip® stem (DePuy Synthes or Aesculap). Varus(+)/Valgus(−) stem alignment was analyzed in postoperative anteroposterior pelvic radiographs. Effects on femoral offset reconstruction and correlation to patient’s individual clinical and radiological parameters were evaluated. Results: 55 stems were implanted in varus (59%), 32 in neutral (34%) and 6 in valgus alignment (7%). Mean stem alignment in varus position was + 2.2° (SD ± 1.4°). Varus alignment was associated with male gender and preoperative coxa vara deformity: low CCD, high femoral offset and long thigh neck (p ≤ 0.001). Alignment was not correlated to femoral offset restoration, BMI or leg length difference. Mean cup inclination was 44° (SD ± 4.7°) and 90% matched the coronal Lewinnek safe zone. Conclusion: In the learning curve, the DAA can be associated with a high incidence of varus stem alignment when using a straight tapered stem, especially in men with coxa vara deformity: low CCD, high femoral offset and long thigh neck. An insufficient capsule release makes femur exposure more difficult and might be an additional factor for this finding. We recommend intraoperative X-ray in the learning phase of the DAA to verify correct implant positioning and to adjust offset options. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
    view abstract10.1007/s00402-020-03457-9
  • The learning curve of patient-specific unikondylar arthroplasty may be advantageous to off-the-shelf implants: A preliminary study
    Mayer, C. and Bittersohl, B. and Haversath, M. and Franz, A. and Krauspe, R. and Jäger, M. and Zilkens, C.
    Journal of Orthopaedics 22 (2020)
    Introduction: Introducing a new arthroplasty system into clinical routine is challenging and could have an effect on early results. Since UKA are known to have failure mechanisms related to technical factors, reliable results and easy adoption are ideal. The question remains whether there are differences in objective procedure parameters in the early learning curve of different UKA systems. Methods: two different UKA implants (Biomet Oxford[BO] followed by Conformis iuni[CI]) were introduced consecutively into clinical routine. We retrospectively analyzed the first 20 cases of each implant for one arthroplasty surgeon regarding operating time, correction of the mechanical axis, learning curve parameters, and revision rate of implants for 1.5 years postoperatively. Results: Operating time (BO:98.3 ± 26.3min, CI:83.85 ± 21.8min (p < 0.078)), and tourniquet time differed in favor of the CI implant (BO:97.5 ± 29.5min; CI:73.5 ± 33.2 min; p < 0.017)). Mechanical alignment was restored in boths (preop:BO:mean 2.9°varus, CI:2.7°varus, postop:BOmean1.3°varus, CI:1°varus), while one BO patient and two CI patients were overcorrected. Operating time decreased from the first five implants to implants 16–20 for CI (95.2 ± 18.5min to 69 ± 21.5min, p < 0.076) and BO (130.6 ± 27.6min to 78 ± 17.3min, p < 0.009). Within 18 months of follow-up, 2 BO and 1 CI implants were revised. Conclusion: The introduction of an UKA implant was associated with longer surgery in both implants. Procedure time seems to differ between implants, while a learning curve was observed regarding instrumentation. CI implants seem to be reliable and adaptable in a medium-volume practice. The early results of this retrospective single-surgeon study were in favor of the individualized implant. Certainly, further studies encompassing larger cohorts with various implants are needed. © 2020 Professor P K Surendran Memorial Education Foundation
    view abstract10.1016/j.jor.2020.05.005
  • U-net in constraint few-shot settings: enforcing few-sample-fitting for faster convergence of u-net for femur segmentation in X-ray
    Pham, D.D. and Lausen, M. and Dovletov, G. and Serong, S. and Landgraeber, S. and Jäger, M. and Pauli, J.
    Informatik aktuell (2020)
    In this paper, we investigate the feasibility of using a standard U-Net for Few-Shot segmentation tasks in very constraint settings. We demonstrate on the example of femur segmentation in X-ray images, that a U-Net architecture only needs few samples to generate accurate segmentations, if the images and the structure of interest only show little variance in appearance and perspective. This is often the case in medical imaging. We also present a novel training strategy for the UNet, leveraging U-Net’s Few-Shot capability for inter-patient consistent protocols. We propose repeatedly enforcing Few-Sample-Fitting the network for faster convergence. The results of our experiments indicate that incrementally fitting the network to an increasing sample set can lead to faster network convergence in constraint few-shot settings. © Springer Fachmedien Wiesbaden GmbH, ein Teil von Springer Nature 2020.
    view abstract10.1007/978-3-658-29267-6_62
  • Vitamin E-blended highly cross-linked polyethylene liners in total hip arthroplasty: a randomized, multicenter trial using virtual CAD-based wear analysis at 5-year follow-up
    Busch, A. and Jäger, M. and Klebingat, S. and Baghdadi, J. and Flörkemeier, T. and Hütter, F. and Grupp, T.M. and Haversath, M. and VITAS-Group
    Archives of Orthopaedic and Trauma Surgery 140 (2020)
    Background: Progressive oxidation of highly cross-linked ultra-high molecular weight (UHMPWE-X) liners is considered to be a risk factor for material failure in THA. Antioxidants such as vitamin E (alpha-tocopherol) (UHMWPE-XE) were supplemented into the latest generation of polyethylene liners. To prevent inhomogenous vitamin E distribution within the polymer, blending was established as an alternative manufacturing process to diffusion. The purpose of the present study was to investigate the in vivo wear behavior of UHMWPE-XE in comparison with conventional UHMWPE-X liners using virtual CAD-based radiographs. Methods: Until now, 94 patients from a prospective, randomized, controlled, multicenter study were reviewed at 5-year follow-up. Of these, 51 (54%) received UHMWPE-XE and 43 (46%) UHMWPE-X liners. Anteroposterior pelvic radiographs were made immediately after surgery and at 1 and 5 years postoperatively. The radiographs were analyzed using the observer-independent analysis software RayMatch® (Raylytic GmbH, Leipzig, Germany). Results: The mean wear rate was measured to be 23.6 μm/year (SD 13.7; range 0.7–71.8 μm). There were no significant differences between the two cohorts (UHMWPE-X: 23.2 μm/year vs. UHMWPE-XE: 24.0 μm/year, p = 0.73). Cup anteversion significantly changed within the 1st year after implantation independent from the type of polyethylene liner [UHMWPE-X: 18.2–23.9° (p = 0.0001); UHMWPE-XE: 21.0–25.5° (p = 0.002)]. No further significant changes of cup anteversion in both groups were found between year 1 and 5 after implantation [UHMWPE-X (p = 0.46); UHMWPE-XE (p = 0.56)]. Conclusion: The present study demonstrates that the addition of vitamin E does not adversely affect the midterm wear behavior of UHMWPE-X. The antioxidative benefit of vitamin E is expected to become evident in long-term follow-up. Cup anteversion increment by 5° within the 1st year is likely a result of the released hip flexion contracture resulting in an enhanced posterior pelvic tilt. Therefore, a reassessment of target values in acetabular cup placement might be considered. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
    view abstract10.1007/s00402-020-03358-x
  • Vitamin E-blended versus conventional polyethylene liners in prostheses: Prospective, randomized trial with 3-year follow-up [Vitamin-E-vermischte vs. konventionelle Polyethyleninlays in der Prothetik: Prospektive, randomisierte Studie mit 3-Jahres-Follow-up]
    Busch, A. and Jäger, M. and Jäger, M. and Landgraeber, S. and Serong, S. and Haversath, M. and vonWasen, A. and Windhagen, H. and Flörkemeier, T. and Budde, S. and Kubilay, J. and Noll, Y. and Delank, K.S. and Baghdadi, J. and Willburger, R. and Dücker, M. and Wilke, A. and Hütter, F. and Wegner, A. and Haversath, M. and VITAS group
    Orthopade 49 (2020)
    Background: Despite continuous technical improvements, polyethylene wear debris induced periprosthetic osteolysis remains the main cause for failure of hip arthroplasty. Progressive oxidation of polyethylene was identified as another risk factor for material failure. To overcome this problem, antioxidants such as vitamin E (alpha-tocopherol) were supplemented by diffusion into the latest generation of polyethylene liners. Objective: The purpose of the present study was to investigate the clinical outcome of patients treated with vitamin E blended highly cross-linked ultra-high molecular weight polyethylene liners (UHMWPE-XE) in comparison with conventional UHMWPE‑X liners by evaluating patient-reported outcome measures (PROM’s) at 3‑year follow-up. Methods: A total of 143 patients were recruited into this prospective, randomized trial in our academic center. Three years after implantation, 101 patients were examined in the outpatient clinic for follow-up. Of these, 51 (50.5%) received UHMWPE-XE and 50 (49.5%) UHMWPE‑X liners. Clinical outcome was evaluated using Harris-Hip-Score (HHS) UCLA-Score and Hip Disability and Osteoarthritis Outcome Score (HOOS). Results: There was a significant improvement in all PROM’s at one- and three-year follow-up compared to the status before implantation. PROM’s did not differ significantly between the first and third year follow-up. Both liner groups showed an equal clinical outcome. Conclusion: The present study demonstrates that the supplementation of vitamin E to polyethylene liners is reliable and safe without showing higher complication rates compared with conventional polyethylene liners. The shortterm clinical outcome of vitamin E-blended (UHMWPE‑XE) is equivalent to those of conventional highly cross-linked polyethylene liners. © 2019, Springer Medizin Verlag GmbH, ein Teil von Springer Nature.
    view abstract10.1007/s00132-019-03830-6
  • A network of trans-cortical capillaries as mainstay for blood circulation in long bones
    Grüneboom, A. and Hawwari, I. and Weidner, D. and Culemann, S. and Müller, S. and Henneberg, S. and Brenzel, A. and Merz, S. and Bornemann, L. and Zec, K. and Wuelling, M. and Kling, L. and Hasenberg, M. and Voortmann, S. and Lang, S. and Baum, W. and Ohs, A. and Kraff, O. and Quick, H.H. and Jäger, M. and Landgraeber, S. and Dudda, M. and Danuser, R. and Stein, J.V. and Rohde, M. and Gelse, K. and Garbe, A.I. and Adamczyk, A. and Westendorf, A.M. and Hoffmann, D. and Christiansen, S. and Engel, D.R. and Vortkamp, A. and Krönke, G. and Herrmann, M. and Kamradt, T. and Schett, G. and Hasenberg, A. and Gunzer, M.
    Nature Metabolism 1 (2019)
    Closed circulatory systems underlie the function of vertebrate organs, but in long bones their structure is unclear although they constitute the exit route for bone marrow (BM) leukocytes. To understand neutrophil migration from BM, we studied the vascular system of murine long bones. Here, in a mouse model, we show that hundreds of capillaries originate in BM, traverse cortical bone perpendicularly along the shaft and connect to the periosteal circulation. Structures similar to these trans-cortical vessels (TCVs) also exist in human limb bones. TCVs express arterial or venous markers and transport neutrophils. Furthermore, over 80% of arterial and 59% of venous blood passes through TCVs. Genetic and drug-mediated modulation of osteoclast count and activity leads to substantial changes in TCV numbers. In a murine model of chronic arthritic bone inflammation, new TCVs develop within weeks. Our data indicate that TCVs are a central component of the closed circulatory system in long bones and may represent an important route for immune cell export from BM. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.
    view abstract10.1038/s42255-018-0016-5
  • Apps in clinical use in orthopedics and trauma surgery: The status quo in Germany [Klinischer Einsatz mobiler Applikationen in der Orthopädie und Unfallchirurgie in Deutschland: Eine Bestandsaufnahme]
    Dittrich, F. and Busch, A. and Harren, K. and Jäger, M. and Landgraeber, S. and Reinecke, F. and Beck, S.
    Unfallchirurg 122 (2019)
    In the course of digitalization the smartphone is penetrating more and more areas of life giving the user mobile and almost ubiquitous access to the internet and other web applications. The advantages of mHealth are an integral part in some areas of patient care but in contrast to other disciplines, routine integration of mobile devices into orthopedics and trauma surgery is still in its infancy. A survey among German orthopedists and trauma surgeons revealed which kind of apps have become established in everyday clinical practice to date. Apps published by representative institutions such as the AO Foundation demonstrated the highest usage rates. In summary, the number of regularly used apps is low; however, the causes of this lack of acceptance have not yet been conclusively clarified. The authors of this study proclaim a significant increase in the use of mHealth and mobile devices in daily clinical practice in the future. © 2019, Springer Medizin Verlag GmbH, ein Teil von Springer Nature.
    view abstract10.1007/s00113-019-0675-z
  • Atraumatic fractures of the spine: Current strategies for diagnosis and treatment [Atraumatische Frakturen der Wirbelsäule: Aktuelle Strategien zur Diagnose und Therapie]
    Tassemeier, T. and Haversath, M. and Brandenburger, D. and Schutzbach, M. and Serong, S. and Jäger, M.
    Orthopade 48 (2019)
    Atraumatic fractures of the spine are a common orthopedic disease condition that can be asymptomatic or associated with complaints of varying intensity and quality. The risk factors for such fracture forms are often metabolic and genetic diseases, which have a direct or indirect effect on bone metabolism and therefore secondarily affect the stability of the spinal vertebrae. Furthermore, benign and malignant tumors as well as infectious diseases can also be causative for atraumatic spinal fractures; however, those factors that are attributable to lifestyle habits should also not be underestimated. The treatment of affected patients is complex and nearly always interdisciplinary. In addition to purely symptom-oriented treatment concepts, orthoses in particular and when indicated surgical treatment procedures can be implemented. This article summarizes the important clinical, diagnostic and therapeutic aspects of atraumatic spinal fractures. © 2019, Springer Medizin Verlag GmbH, ein Teil von Springer Nature.
    view abstract10.1007/s00132-019-03804-8
  • Biomechanical stability and osteogenesis in a tibial bone defect treated by autologous ovine cord blood cells—a pilot study
    Herten, M. and Zilkens, C. and Thorey, F. and Tassemeier, T. and Lensing-Höhn, S. and Fischer, J.C. and Sager, M. and Krauspe, R. and Jäger, M.
    Molecules 24 (2019)
    The aim of this study was to elucidate the impact of autologous umbilical cord blood cells (USSC) on bone regeneration and biomechanical stability in an ovine tibial bone defect. Ovine USSC were harvested and characterized. After 12 months, full-size 2.0 cm mid-diaphyseal bone defects were created and stabilized by an external fixateur containing a rigidity measuring device. Defects were filled with (i) autologous USSC on hydroxyapatite (HA) scaffold (test group), (ii) HA scaffold without cells (HA group), or (iii) left empty (control group). Biomechanical measures, standardized X-rays, and systemic response controls were performed regularly. After six months, bone regeneration was evaluated histomorphometrically and labeled USSC were tracked. In all groups, the torsion distance decreased over time, and radiographies showed comparable bone regeneration. The area of newly formed bone was 82.5 ± 5.5% in the control compared to 59.2 ± 13.0% in the test and 48.6 ± 2.9% in the HA group. Labeled cells could be detected in lymph nodes, liver and pancreas without any signs of tumor formation. Although biomechanical stability was reached earliest in the test group with autologous USSC on HA scaffold, the density of newly formed bone was superior in the control group without any bovine HA. © 2019 by the authors.
    view abstract10.3390/molecules24020295
  • Circulating growth/differentiation factor 15 is associated with human CD56bright natural killer cell dysfunction and nosocomial infection in severe systemic inflammation
    Kleinertz, H. and Hepner-Schefczyk, M. and Ehnert, S. and Claus, M. and Halbgebauer, R. and Boller, L. and Huber-Lang, M. and Cinelli, P. and Kirschning, C. and Flohé, S. and Sander, A. and Waydhas, C. and Vonderhagen, S. and Jäger, M. and Dudda, M. and Watzl, C. and Flohé, S.B.
    EBioMedicine 43 (2019)
    Background: Systemic inflammation induced by sterile or infectious insults is associated with an enhanced susceptibility to life-threatening opportunistic, mostly bacterial, infections due to unknown pathogenesis. Natural killer (NK) cells contribute to the defence against bacterial infections through the release of Interferon (IFN) γ in response to Interleukin (IL) 12. Considering the relevance of NK cells in the immune defence we investigated whether the function of NK cells is disturbed in patients suffering from serious systemic inflammation. Methods: NK cells from severely injured patients were analysed from the first day after the initial inflammatory insult until the day of discharge in terms of IL-12 receptor signalling and IFN-γ synthesis. Findings: During systemic inflammation, the expression of the IL-12 receptor β2 chain, phosphorylation of signal transducer and activation 4, and IFN-γ production on/in NK cells was impaired upon exposure to Staphylococcus aureus. The profound suppression of NK cells developed within 24 h after the initial insult and persisted for several weeks. NK cells displayed signs of exhaustion. Extrinsic changes were mediated by the early and long-lasting presence of growth/differentiation factor (GDF) 15 in the circulation that signalled through the transforming growth factor β receptor I and activated Smad1/5. Moreover, the concentration of GDF-15 in the serum inversely correlated with the IL-12 receptor β2 expression on NK cells and was enhanced in patients who later acquired septic complications. Interpretation: GDF-15 is associated with the development of NK cell dysfunction during systemic inflammation and might represent a novel target to prevent nosocomial infections. Fund: The study was supported by the Department of Orthopaedics and Trauma Surgery, University Hospital Essen. © 2019 The Authors
    view abstract10.1016/j.ebiom.2019.04.018
  • Computed-tomography-guided biopsy in suspected spondylodiscitis: Single-center experience including 201 biopsy procedures
    Özmen, D. and Özkan, N. and Guberina, N. and Fliessbach, K. and Suntharalingam, S. and Theysohn, J. and Büchter, M. and Forsting, M. and Buer, J. and Dudda, M. and Jäger, M. and Wetter, A.
    Orthopedic Reviews 11 (2019)
    Our propose is to evaluate CT-guided biopsies in suspected spondylodiscitis with respect to puncture site, microbiology findings, histopathology findings and impact on antibiotic therapy. 86 CT-guided spine interventions in suspected spondylodiscitis comprising 201 biopsy procedures were analyzed. Medical records of all patients were screened for microbiology and histopathology reports as well as date, duration and kind of antibiotic therapy. Statistical analyses included calculation of Chi2-tests and logistic regression analyses. Locations of biopsies were intervertebral disc (48.3%), paravertebral soft-tissue (38.3%) and vertebral body (10.9%). Positive microbiological findings were found altogether in 33.8% of cases, positive histopathological findings in 53.6%. Significant associations between positive microbiological findings, positive histopathological findings and antibiotic therapy, respectively, were found. Location of biopsies did not significantly influence rate of positive findings. From the variables age, white blood cell count, serum creatinine and puncture site, none were found to be an independent predictor for a positive microbiological result. We concluded that CT-guided biopsy of intervertebral disc and paravertebral soft tissue yields positive microbiologic findings in a significant proportion of cases. Puncture site is not associated with positive results of microbiology or histopathology. © D. Özmen et al., 2019.
    view abstract10.4081/or.2019.7793
  • Current trends and injuries in cycling: faster, further, e-bike? [Trends und Verletzungen im Radsport: schneller, weiter, E‑Bike?]
    Hinder, J. and Jäger, M.
    Orthopade 48 (2019)
    During the past decade, technical innovations (e.g., carbon as a new material, disk brakes, hydraulic shock absorbers, electric transmissions) and lifestyle changes have significantly influenced recreational and professional cycling. In contrast to the past, where ambitious leisure cyclists were primarily interested in the recreational value of nature and landscape, cyclists of all ages are nowadays increasingly focused on performance and self-optimization. Simultaneously, manufacturers have adapted to differing customer requirements: besides the traditional extremities of road and mountain bikes, many specialized models have been designed for special applications: trekking, cyclocross, gravel, full-suspension, single-track, hardtail, downhill, fatbike, etc. For biking fans who are no longer able to meet their own demands due to individual physical restrictions or defined health problems, electric-assist bikes (pedelecs or “e-bikes”) were recently introduced. While these are becoming increasingly popular, they have also increased the number of accidents and injuries. The current work provides an update on relevant sport medical and orthopaedic challenges brought on by these developments in cycling. © 2019, Springer Medizin Verlag GmbH, ein Teil von Springer Nature.
    view abstract10.1007/s00132-019-03824-4
  • Deep learning with anatomical priors: Imitating enhanced autoencoders in latent space for improved pelvic bone segmentation in MRI
    Pham, D.D. and Dovletov, G. and Warwas, S. and Landgraeber, S. and Jager, M. and Pauli, J.
    Proceedings - International Symposium on Biomedical Imaging 2019-April (2019)
    We propose a 2D Encoder-Decoder based deep learning architecture for semantic segmentation, that incorporates anatomical priors by imitating the encoder component of an autoencoder in latent space. The autoencoder is additionally enhanced by means of hierarchical features, extracted by an UNet module. Our suggested architecture is trained in an end-to-end manner and is evaluated on the example of pelvic bone segmentation in MRI. A comparison to the standard U-Net architecture shows promising improvements. © 2019 IEEE.
    view abstract10.1109/ISBI.2019.8759221
  • Deep segmentation refinement with result-dependent learning: A double U-net for hip joint segmentation in MRI
    Pham, D.D. and Dovletov, G. and Warwas, S. and Landgraeber, S. and Jäger, M. and Pauli, J.
    Informatik aktuell (2019)
    In this contribution, we propose a 2D deep segmentation refinement approach, that is inspired by the U-Net architecture and incorporates result-dependent loss adaptation. The performance of our method regarding segmentation quality is evaluated on the example of hip joint segmentation in T1-weighted MRI data sets. The results are compared to an ordinary U-Net implementation. While the segmentation quality of the proximal femur does not significantly change, our proposed method shows promising improvements for the segmentation of the pelvic bone complex, which shows more shape variability in the 2D image slices along the longitudinal axis. © 2019, Springer Berlin Heidelberg. All rights reserved.
    view abstract10.1007/978-3-658-25326-4_14
  • Doping in elite and popular sport: What orthopedic and trauma surgeons should know [Doping im Spitzen- und Breitensport: Was der Orthopäde und Unfallchirurg wissen sollten]
    Husen, M. and Jäger, M.
    Orthopade 48 (2019)
    The spectacular doping raid during the Nordic World Ski Championships in Seefeld in winter this year is not the first time that illegal performance enhancement by taking drugs is in the spotlight of public interest. Kicked off by the so-called Festina scandal of the 1998 Tour de France, the serial exposure of further doping offences continues up to the present day. Less well-known to the general public is the high prevalence of doping under hobby and amateur athletes. Physicians are confronted by this group of patients in the practice much more frequently than by elite athletes, who are mostly treated in closed medical networks. The aim of the article is to provide an overview of the medical aspects including the most frequent substance classes and the current legal foundations of the anti-doping movement. Furthermore, the official definition of doping and the structure of the anti-doping agencies are presented. © 2019, Springer Medizin Verlag GmbH, ein Teil von Springer Nature.
    view abstract10.1007/s00132-019-03780-z
  • Functional knee stability in handball: An indispensable criterion for safe sport [Funktionelle Kniestabilität im Handball: Ein unverzichtbares Kriterium für sicheren Sport]
    Rühlemann, A. and Mayer, C.U. and Götte, L. and Behringer, M. and Jäger, M.
    Sportverletzung-Sportschaden 33 (2019)
    Various studies in recent years have shown that, within ball sports, handball players have a high risk of accidents and injuries. The knee joint is the most frequently injured body region, and ruptures of the anterior cruciate ligament the most common injury to the knee. To prevent consequential damage or recurrent knee injury, good functional stability of the knee is of high importance. Stability not only prevents injuries, but is also crucial for optimising handball-specific movements. Although there are numerous studies on injuries in handball-mostly performed on professional athletes-the field of research focusing on functional knee stability is deficient. This article provides an overview of the current state of research and discusses existing prevention approaches. © 2019 Georg Thieme Verlag KG, Stuttgart • New York.
    view abstract10.1055/a-0753-2285
  • Gradient-Based Expanding Spherical Appearance Models for Femoral Model Initialization in MRI
    Pham, D.D. and Dovletov, G. and Warwas, S. and Landgraeber, S. and Jäger, M. and Pauli, J.
    Informatik aktuell (2019)
    While deep learning strategies for semantic segmentation increasingly take center stage, traditional approaches seem to take a backseat. However, in the domain of medical image processing, labeled training data is rare and expensive to acquire. Thus, traditional methods may still be preferable to deep learning approaches. Many of these conventional approaches often require initial localization of the structure of interest (SOI) to provide satisfactory results. In this work we present a fully automatic model initialization approach in MRI, that is applicable for anatomical structures that contain a near-spherical component. We propose a model, that encapsulates the difference between intensity distribution within the SOI�s spherical component and its proximity. We present our approach on the example of femoral model initialization and compare our initialization results to a diffeomorphic demons registration approach. © 2019, Springer Berlin Heidelberg. All rights reserved.
    view abstract10.1007/978-3-658-25326-4_13
  • Handball injuries and their prevention [Verletzungen und deren Prävention beim Handball]
    Mayer, C. and Rühlemann, A. and Jäger, M.
    Orthopade 48 (2019)
    Background: Handball is one of the most popular team sports in Germany, as well as one of the most dangerous ones. Injury rates in Germany are higher amongst handball professionals than in soccer, with the knee being the most commonly injured joint. To prevent injuries, a functional inert stability is necessary, but definitions and objective measures are lacking. Objectives: Establishing valid reference data of functional knee stability in amateur handball players with use of an established test battery giving objective measures Methods: 261 athletes (f:130; m:131), mean age 25.1 ± 5.8 y were screened during the preseason. The test battery consisted of double and single-leg counter movement jumps, balance tests, agility, parkour, quick feet test and plyometric jumps. Results: Significant differences between males and females were noted in regard to balance scores (favour for females p ≤ 0.001), as well as jump height, agility and speed tests (favour for males [p ≤ 0.002–0.001]). Conclusion: The noted differences once again bring focus to the interindividual presence of risk factors, because female and male handball athletes have gender-specific ground levels. These attributes have to be considered in further screening and prevention programs, as well as in the context of the return-to-sports decision after injury. The given data may serve as objective reference measures. © 2019, Springer Medizin Verlag GmbH, ein Teil von Springer Nature.
    view abstract10.1007/s00132-019-03822-6
  • Intrasurgical Protein Layer on Titanium Arthroplasty Explants: From the Big Twelve to the Implant Proteome
    Jäger, M. and Jennissen, H.P. and Haversath, M. and Busch, A. and Grupp, T. and Sowislok, A. and Herten, M.
    Proteomics - Clinical Applications 13 (2019)
    Purpose: Aseptic loosening in total joint replacement due to insufficient osteointegration is an unsolved problem in orthopaedics. The purpose of the study is to obtain a picture of the initial protein adsorption layer on femoral endoprosthetic surfaces as the key to the initiation of osseointegration. Experimental design: The paper describes the first study of femoral stem explants from patients for proteome analysis of the primary protein layer. After 2 min in situ, the stems are explanted and frozen in liquid nitrogen. Proteins are eluted under reducing conditions and analyzed by LC-MS/MS. Results: After exclusion of proteins identified by a single peptide, the implant proteome is found to consist of 2802 unique proteins. Of these, 77% are of intracellular origin, 9% are derived from the plasma proteome, 8% from the bone proteome, and four proteins with highest specificity score could be assigned to the bone marrow proteome (transcriptome). The most abundant protein in the adsorbed total protein layer is hemoglobin (8–11%) followed by serum albumin (3.6–6%). Conclusions: A detailed knowledge of the initial protein film deposited onto the implants, as demonstrated here for the first time, may help to understand and predict the response of the osseous microenvironment to implant surfaces. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
    view abstract10.1002/prca.201800168
  • Long-term results of the reverse Total Evolutive Shoulder System (TESS)
    Beck, S. and Patsalis, T. and Busch, A. and Dittrich, F. and Dudda, M. and Jäger, M. and Wegner, A.
    Archives of Orthopaedic and Trauma Surgery 139 (2019)
    Introduction: Latest trends in shoulder replacement aim at bone stock preservation. Long-term results of stemless anatomical total shoulder implants compare favourably with stemmed designs in terms of function and survivorship. The Total Evolutive Shoulder System (TESS) has been one of the first designs offering a stemless implant not only for anatomical but also for reverse total shoulder arthroplasty with optional short stem attachment in cases with poor bone quality. The aim of the present study was to evaluate long-term results of the reverse Total Evolutive Shoulder System (TESS). Materials and methods: Between 2006 and 2009, 49 shoulders in 47 patients were replaced using the Biomet reverse Total Evolutive Shoulder System (TESS). 29 shoulders in 27 patients who were aged 72.4 ± 6.7 (53–88) years were available for review at a mean follow-up of 101.6 ± 24.6 (75–142) months. Results: The implant survival rate was 93.1% at 101 months (8.4 years). The overall revision rate of the TESS implant was 17.2%. No implant associated complications to the reverse corolla implant could be observed. All reverse corolla implants showed solid fixation at follow-up. Scapular notching was found in 72.3% of the shoulders. Clinical scores significantly improved at long-term follow-up (VAS from 7.5 ± 1.2 to 1.4 ± 1.5, p < 0.001; quick-DASH from 70.9 ± 12.0 to 28.9 ± 22.9, p < 0.001 and Constant score from 13.0 ± 3.7 to 60.5 ± 16.8, p < 0.001). Conclusions: In terms of clinical scores, radiographic loosening, complication rates and implant survivorship the reverse Total Evolutive Shoulder System provides results comparable to those of conventional stemmed reverse shoulder arthroplasty. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
    view abstract10.1007/s00402-019-03135-5
  • Prevalence of CAM deformity and its influence on therapy success in patients with osteonecrosis of the femoral head
    Serong, S. and Haversath, M. and Jäger, M. and Landgraeber, S.
    Journal of Tissue Engineering and Regenerative Medicine 13 (2019)
    Osteonecrosis of the femoral head (ONFH) and CAM-type femoroacetabular impingement (FAI) present two different pathologies of the hip joint. The aim of this study is to describe the prevalence of CAM-FAI in a collective of ONFH hips and to evaluate its influence on ONFH therapy outcome. A cohort of 86 ONFH hips with a mean follow-up of 46.7 months (±20.5) after advanced core decompression (ACD) was evaluated regarding CAM deformity by measuring the alpha angle (α) and head–neck offset. The influence of CAM-type FAI was investigated using the Kaplan–Meier estimator and the Cox regression model. The mean α was 60.4° (±13.8) with 41 hips (47.7%) being ≥60°. The mean head–neck offset was 4.5 mm (±3.2), with 78 hips (90.7%) being ≤9 mm. Survival analysis indicated noticeably better ACD results for α < 60° versus α ≥ 60° (p = 0.07). Treatment failure within the first 2 years was statistically estimated as 27.7% for α < 60° versus 40.7% for α ≥ 60°: The hazard ratio for α ≥ 60° was 1.94. Head–neck offset-dependent survival showed better, though not significant, results for offset >9 mm (p = 0.38, hazard ratio 1.89 for offsets ≤9 mm). The prevalence of CAM-type deformity is greatly increased in patients with concomitant ONFH. There is a strong indication that CAM-type FAI has a negative influence on ONFH therapy outcome. The risk that ONFH treatment will fail seems to be twice as high for α ≥ 60° as for α < 60°. We recommend cotreatment of pathological head–neck offset in patients with ONFH. © 2019 John Wiley & Sons, Ltd.
    view abstract10.1002/term.2794
  • Slow as Compared to Rapid Rewarming After Mild Hypothermia Improves Survival in Experimental Shock
    Burggraf, M. and Lendemans, S. and Waack, I.N. and Teloh, J.K. and Effenberger-Neidnicht, K. and Jäger, M. and Rohrig, R.
    Journal of Surgical Research 236 (2019)
    Background: Accidental hypothermia following trauma is an independent risk factor for mortality. However, in most experimental studies, hypothermia clearly improves outcome. We hypothesized that slow rewarming is beneficial over rapid rewarming following mild hypothermia in a rodent model of hemorrhagic shock. Materials and methods: We subjected 32 male Wistar rats to severe hemorrhagic shock (25–30 mmHg for 30 min). Rats were assigned to four experimental groups (normothermia, hypothermia, rapid rewarming [RW], and slow RW). During induction of severe shock, all but the normothermia group were cooled to 34°C. After 60 min of shock, rats were resuscitated with Ringer's solution. The two RW groups were rewarmed at differing rates (6°C/h versus 2°C/h). Results: Slow RW animals exhibit a significantly prolonged survival compared with the rapid RW animals (P < 0.05). Nevertheless, hypothermic animals show a significant survival benefit as compared to all other experimental groups. Whereas seven animals of the hypothermia group survived to the end of the experiment, none of the other animals did (P < 0.001). No significant differences were found regarding acid base status, metabolism, parameters of organ injury, and coagulation. Conclusions: The results indicate that even slow RW with 2°C/h may be still too fast in the setting of experimental hemorrhage. Too rapid rewarming may result in a loss of the protective effects of hypothermia. As rewarming is ultimately inevitable in patients with trauma, potential effects of rewarming on patient outcome should be further investigated in clinical studies. © 2018 Elsevier Inc.
    view abstract10.1016/j.jss.2018.11.057
  • Sport: higher, faster, further … [Sport: Höher, schneller, weiter …]
    Jäger, M.
    Der Orthopade 48 (2019)
    view abstract10.1007/s00132-019-03828-0
  • Surgical vacuum filter-derived stromal cells are superior in proliferation to human bone marrow aspirate
    Henze, K. and Herten, M. and Haversath, M. and Busch, A. and Brandau, S. and Hackel, A. and Flohé, S.B. and Jäger, M.
    Stem Cell Research and Therapy 10 (2019)
    Background: During joint replacement, surgical vacuum suction guarantees a sufficient overview on the situs. We assume high concentrations of mesenchymal stromal cells (MSCs) on surgical vacuum filters. We compared the in vitro proliferative and differentiation potency of cells from the following: (i) bone marrow (BM), (ii) cancellous bone (CB), (iii) vacuum filter (VF), and (iv) cell saver filtrate reservoir (SF) in 32 patients undergoing elective total hip replacement. Methods: Mononuclear cells (MNC) were isolated, and cell proliferation and colony-forming units (CFU) were measured. Adherent cells were characterized by flow cytometry for MSC surface markers. Cells were incubated with osteogenic, adipogenic, and chondrogenic stimuli. Cells were cytochemically stained and osteoblastic expression (RUNX-2, ALP, and BMP-2) investigated via qPCR. Results: Dependent on the source, initial MNC amount as well as CFU number was significantly different whereas generation time did not vary significantly. CFU numbers from VF were superior to those from SR, BM, and CB. The resulting amount of MSC from the respective source was highest in the vacuum filter followed by reservoir, aspirate, and cancellous bone. Cells from all groups could be differentiated into the three mesenchymal lines demonstrating their stemness nature. However, gene expression of osteoblastic markers did not differ significantly between the groups. Conclusion: We conclude that surgical vacuum filters are able to concentrate tissue with relevant amounts of MSCs. A new potent source of autologous regeneration material with clinical significance is identified. Further clinical studies have to elucidate the regenerative potential of this material in an autologous setting. © 2019 The Author(s).
    view abstract10.1186/s13287-019-1461-0
  • The 'critical trochanter angle': A predictor for stem alignment in total hip arthroplasty
    Haversath, M. and Busch, A. and Jäger, M. and Tassemeier, T. and Brandenburger, D. and Serong, S.
    Journal of Orthopaedic Surgery and Research 14 (2019)
    Introduction: Stem malalignment can affect offset reconstruction and may result in gluteal muscle insufficiency. In this retrospective study, a novel geometric angle named 'critical trochanter angle' (CTA) is described and investigated towards the risk of malposition of a collarless straight tapered hydroxyapatite-coated stem in primary total hip arthroplasty (THA). Material and methods: A total of 100 cementless THA were implanted in patients with unilateral coxarthrosis via the direct anterior (n = 50) or direct lateral Hardinge approach (n = 50) in a two surgeon setting using the Corail® or Trendhip® stem (DePuy Synthes or Aesculap). Stem alignment was analysed in postoperative AP pelvic radiographs and correlated to the CTA: the angle crest was defined by the intersection of the femoral shaft and neck axis and the angle was measured between the shaft axis and a leg intersecting the vertex between the lateral and superoposterior facet of the trochanter. Results: Forty-seven stems were implanted in varus (≥ + 1°), 42 in neutral (< + 1°/> - 1°) and 11 in valgus position (≤ - 1°). The mean critical trochanter angle was 25.0° (SD ± 7.5°), and there was a negative and statistically significant correlation to stem alignment (r = - 0.52; p ≤ 0.001) independent from the surgical approach. For stem malposition of 2° and above (n = 23), mean CTA was 17.2° for varus (n = 20) and 31.6° for valgus (n = 3). A CTA lesser or equal to 22.75° had a sensitivity of 90% and specificity of 80% for varus stem position of 2° or greater. Specificity raised to 100% with a cutoff CTA of 12.5° or lesser. Conclusion: Varus stem alignment in THA is associated with coxa vara deformity and a radiological low CTA. In preoperative planning, the critical trochanter angle can help to evaluate the risk for intraoperative stem malpositioning. If navigation or robotic assistance is not available when using this stem design, we recommend an intraoperative x-ray to verify correct implant positioning in patients with a CTA under 20° or above 30°. © 2019 The Author(s).
    view abstract10.1186/s13018-019-1206-x
  • The influence of ABO blood group on mortality in major trauma
    Hamsen, U. and Nohl, A. and Baumann, A. and Lefering, R. and Boutakmant, L. and Waydhas, C. and Dudda, M. and Schildhauer, T.A. and Jäger, M. and Wegner, A.
    Orthopedic Reviews 11 (2019)
    ABO blood group has a profound influence on hemostasis as it is a major determinant of plasma levels of von Willebrand Factor. In vitro studies suggest that blood group O is a risk factor for increased severe bleeding while blood group non-O is a risk factor for thromboembolic events. Yet, the impact of ABO blood group outcome after multiple trauma is unknown. Retrospective multicenter case-control study from three level-1 trauma centers in Germany from 2012-2015. Inclusion criteria were severe trauma with an Injury severity score ≥9 and admission to an intensive care unit. 1281 patients (69.5% male) were included. Mean Injury Severity Score (ISS) was 21.1±12.4; mean age was 50.2±22.4 years. Distribution of blood groups was: O: 37.4%; A: 44%, B: 12.7 and AB: 5.8%. Hospital mortality depending on blood group was 9.7 (A), 10.4 (B), 6.8 (AB) and 12.7 (O) %. Multivariant logistic regression for mortality revealed an Odds ratio of 0.79 (A), 0.60 (B) and 0.54 (AB) without statistical significance (P=0.35 (A), 0.17 (B), 0.33 (AB)). Thromboembolic events (blood group O vs. others) occurred in 2.8 (O) vs. 3.3 (others) %, P=0.619. Non In this retrospective study on 1281 multiple injured patients, no relevant influence of ABO blood group on hemorrhage, thromboembolic events and mortality could be found. © the Author(s), 2019 Licensee PAGEPress, Italy.
    view abstract10.4081/or.2019.8214
  • The influence of chronic kidney disease on the duration of hospitalisation and transfusion rate after elective hip and knee arthroplasty
    Kaiser, C. and Tillmann, F.P. and Löchter, J. and Landgraeber, S. and Jäger, M.
    International Urology and Nephrology 51 (2019)
    Purpose: Elective hip or knee replacement is an optimal, standardised orthopaedic surgical procedure. The influence of chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) of 15–45 ml/min/1.73 m 2 body surface area (BSA) (KDIGO stage G3a-G4), on the duration of hospitalisation, perioperative decrease in haemoglobin (Hb) levels, and transfusion rates after orthopaedic procedures has not been fully clarified. Our study, therefore, aimed to evaluate the impact of chronic kidney disease on the previously mentioned variables. Methods: We conducted a retrospective multicentre analysis involving two orthopaedic centres. Patients who underwent elective total hip and knee replacement between 2010 and 2015 were included. We used descriptive methods and multivariate linear and binary regression analyses for our statistical evaluations. Results: We evaluated 3301 datasets (1120 men [33.9%], 2181 women [66.1%], 2043 [61.9%], and 1258 [38.1%]) elective total hip and knee replacements, respectively. The following variables were identified as risk factors for a prolonged hospital stay: patient age, admission Hb and potassium levels, perioperative Hb level decrease, year of surgery, blood transfusion, and a preoperative eGFR of 15–45 ml/min/m 2 BSA. Patients with an eGFR of &gt; 45 ml/min/m 2 BSA were discharged within 11.7 ± 3.0 days, while patients with an eGFR of 15–45 ml/min/1.73 m 2 BSA remained inpatient for 13.5 ± 5.0 days (p &lt; 0.001). Identified risk factors for postoperative blood transfusions included age, initial Hb level, perioperative Hb decrease, prosthetic hip replacement, and the presence of allergic diathesis. Blood transfusions were performed in 7.5% of patients with an eGFR of &gt; 45 ml/min/m 2 BSA compared to 24.1% of patients with an eGFR of 15–45 ml/min/1.73 m 2 BSA (p &lt; 0.001). An eGFR level of 15–45 ml/min/m 2 BSA was identified as a risk factor for a postoperative decrease in Hb levels. Conclusion: Chronic kidney disease, defined as an eGFR level of 15–45 ml/min/1.73 m 2 BSA, was a risk factor for a prolonged hospital stay after elective hip and knee arthroplasty. Further studies are necessary to better define the effect of reduced kidney function on relevant clinical and socioeconomic outcome parameters. © 2018, Springer Nature B.V.
    view abstract10.1007/s11255-018-2008-5
  • Unilateral swelling and functional impairment of unknown origin in the right arm [Unklare unilaterale Schwellung und Funktionseinschränkung des rechten Armes]
    Reinecke, F.C. and Becker, L. and Jäger, M.
    Deutsches Arzteblatt International 116 (2019)
    view abstract10.3238/arztebl.2019.0143
  • Long-term survivorship of stemless anatomical shoulder replacement
    Beck, S. and Beck, V. and Wegner, A. and Dudda, M. and Patsalis, T. and Jäger, M.
    International Orthopaedics 42 (2018)
    Purpose: Like in many other joints, current shoulder replacement designs aim at bone preservation. According to the literature available, stemless total shoulder arthroplasty (TSA) compares favourably with stemmed designs in terms of function and survivorship of the implant. However, long-term results of stemless shoulder arthroplasty are still missing. Therefore, the aim of the present study was to evaluate long-term results of stemless anatomical TSA. Methods: Between 2006 and 2009, 51 shoulders in 46 patients were resurfaced using the Biomet Total Evolutive Shoulder System (TESS). Thirty-one shoulders in 26 patients who were aged 66.7 ± 10.0 (range 34–82) years were available for review at a mean follow-up of 94.7 ± 11.3 (76–124) months. Results: The implant survival rate was 93.5% at eight years. The overall revision rate of the TESS implant was 9.7%. Radiolucent lines were found on the glenoid side of the TESS arthroplasty in 90.9% of the cases. All stemless humeral corolla implants showed solid fixation at follow-up. Clinical scores significantly improved at long-term follow-up (VAS from 8.1 ± 0.9 to 1.0 ± 1.2, p < 0.001; Quick-DASH from 67.9 ± 13.5 to 18.7 ± 16.5, p < 0.001 and Constant score from 14.7 ± 6.1 to 68.8 ± 13.2, p < 0.001). Conclusions: Stemless TSA has stood the test of time at eight years in terms of clinical scores, radiographic loosening, complication rates and implant survivorship. © 2018, SICOT aisbl.
    view abstract10.1007/s00264-018-3779-0
  • Polar appearance models: A fully automatic approach for femoral model initialization in MRI
    Pham, D.D. and Morariu, C.A. and Terheiden, T. and Warwas, S. and Landgraeber, S. and Jager, M. and Pauli, J.
    Proceedings - International Symposium on Biomedical Imaging 2018-April (2018)
    Various segmentation approaches in medical image processing, such as Level Sets, Active Shape Models, and Active Appearance Models require initial localization of the structure of interest (SOI). In this work we present a novel fully automatic model initialization approach in MRI, that is applicable for structures that are mostly convex in the axial plane. We propose a training model, namely the Polar Appearance Model, that encapsulates both the transition from the structure of interest to its vicinity in polar space and the intensity distribution within the structure in euclidean space. We present our approach on the example of femoral model initialization in MRI and compare our results to a standard voxel-based registration approach that allows similarity transformations. © 2018 IEEE.
    view abstract10.1109/ISBI.2018.8363740
  • Surface modifications of implants. Part 1: Material technical and biological principles [Oberflächenmodifikationen von Implantaten. Teil 1: Werkstofftechnische und biologische Grundlagen]
    Jäger, M.
    Orthopade 47 (2018)
    The biological effects of implants in vivo are not only dependent on the implantation site and patient-specific factors but are also influenced by the physicochemical composition and the surface topography of the biomaterial. In cases of permanent implants applied to bone, primary stability, the promotion of rapid osteointegration and antimicrobial properties of the implant are strived for; however, surface modifications are also found on biomaterials which only temporarily come into contact with tissue. These include not only osteosynthesis materials, jig or implant templates but also surgical instruments. This article summarizes the relevant technical principles of materials for the assessment of implant surfaces. Besides technical material-specific and biological principles, different surface modifications for targeted clinical applications are presented. Furthermore, current developmental strategies are outlined. © 2018, Springer Medizin Verlag GmbH, ein Teil von Springer Nature.
    view abstract10.1007/s00132-018-3548-1
  • Surface modifications of implants. Part 2: Clinical application [Oberflächenmodifikationen von Implantaten. Teil 2: Klinische Anwendung]
    Jäger, M.
    Orthopade 47 (2018)
    The chemical composition, surface structure and topography of a biomaterial have an essential influence on the effects of an implant in the human body. In orthopedic and trauma surgery they make a relevant contribution to solve the current and future challenges. Particularly high are the requirements of permanent implants in bone. Besides material aging due to oxidation, implants are subjected to cyclic loading that leads to relevant biomechanical wear and abrasion. To date significant efforts have been made to minimize adverse implant-associated immunoreactions as well as the risk of periprosthetic infections. This review gives an overview of surface modifications of implants designed for clinical application and their effects in vivo. Beside material-specific and biological principles, different surface modifications for distinct clinical applications are presented. Furthermore, current developmental strategies for the targeted clinical application of implant surfaces are outlined. © 2018, Springer Medizin Verlag GmbH, ein Teil von Springer Nature.
    view abstract10.1007/s00132-018-3560-5
  • Wear Kinetics of Highly Cross-Linked and Conventional Polyethylene Are Similar at Medium-term Follow-Up After Primary Total Hip Arthroplasty
    Mayer, C. and Rommelmann, M. and Behringer, M. and Jäger, M. and Krauspe, R. and Zilkens, C.
    Journal of Arthroplasty 33 (2018)
    Background: Wear debris is a major factor in aseptic loosening of total hip arthroplasty. Ultra high molecular weight polyethylene inlays are known for significant wear, and the following generation, highly cross-linked polyethylene (HCLPE), has shown promising in vitro and short-term in vivo results. This study aimed to investigate wear debris of HCLPE liners with ceramic heads after 9 years to reveal the in vivo wear kinetics of this common bearing combination. Methods: Fifty-seven patients (72 hips; 46.5 ± 15.5 years; range 16-76 years) who underwent hip arthroplasty with an HCLPE liner (28- or 32-mm Biolox forte ceramic head) were followed up (mean 9.1 ± 2.4 years; range 3.9-13.8 years). Conventional anteroposterior X-rays were analyzed using Hip Analysis Suite software. Results: Volumetric wear had a mean of 38.67 ± 22.09 mm3/year, 333.08 ± 183.93 mm3 overall, and linear wear was 0.063 ± 0.03 mm/year and 0.546 ± 0.27 mm overall. Male patients had a significantly higher wear rate (46.42 ± 27.68 mm3/year) and total wear (400.71 ± 235.21 mm3). Larger femoral heads had a significantly higher wear rate (43.10 ± 23.93 mm3/year) and total wear (364.23 ± 203.68 mm3). Regression analysis showed a significant cubic relationship (R2 = 0.307) with increasing yearly wear after approximately 108 months postoperatively. Conclusions: HCLPE liners show significant in vivo wear after 9 years. While the total wear compared to ultra high molecular weight polyethylene liners was decreased, the wear kinetics show a comparable course. The increase in wear rate after only 108 months postoperatively is especially alarming. Longer term follow-up is needed to distinguish the long-term superiority of HCLPE liners in polyethylene-ceramic paired hip arthroplasty. © 2018 Elsevier Inc.
    view abstract10.1016/j.arth.2018.03.027
  • A single intraperitoneal injection of bovine fetuin-A attenuates bone resorption in a murine calvarial model of particle-induced osteolysis
    Jablonski, H. and Polan, C. and Wedemeyer, C. and Hilken, G. and Schlepper, R. and Bachmann, H.S. and Grabellus, F. and Dudda, M. and Jäger, M. and Kauther, M.D.
    Bone 105 (2017)
    Particle-induced osteolysis, which by definition is an aseptic inflammatory reaction to implant-derived wear debris eventually leading to local bone destruction, remains the major reason for long-term failure of orthopedic endoprostheses. Fetuin-A, a 66 kDa glycoprotein with diverse functions, is found to be enriched in bone. Besides being an important inhibitor of ectopic calcification, it has been described to influence the production of mediators of inflammation. Furthermore, a regulatory role in bone metabolism has been assigned. In the present study, the influence of a single dose of bovine fetuin-A, intraperitoneally injected in mice subjected to particle-induced osteolysis of the calvaria, was analyzed. Twenty-eight male C57BL/6 mice, twelve weeks of age, were randomly divided into four groups. Groups 2 and 4 were subjected to ultra-high molecular weight polyethylene (UHMWPE) particles placed on their calvariae while groups 1 and 3 were sham-operated. Furthermore, groups 3 and 4 received a single intraperitoneal injection of 20 mg bovine fetuin-A while groups 1 and 2 were treated with physiologic saline. After 14 days calvarial bone was qualitatively and quantitatively assessed using microcomputed tomography (μCT) and histomorphometrical approaches. Application of fetuin-A led to a reduction of particle-induced osteolysis in terms of visible osteolytic lesions and eroded bone surface. The reduction of bone thickness and bone volume, as elicited by UHMWPE, was alleviated by fetuin-A. In conclusion, fetuin-A was found to exert an anti-resorptive effect on particle-induced osteolysis in-vivo. Thus, fetuin-A could play a potentially osteoprotective role in the treatment of bone metabolic disorders. © 2017 Elsevier Inc.
    view abstract10.1016/j.bone.2017.09.006
  • Antimicrobial and osseointegration properties of nanostructured titanium orthopaedic implans
    Jäger, M. and Jennissen, H.P. and Dittrich, F. and Fischer, A. and Köhling, H.L.
    Materials 10 (2017)
    The surface design of titanium implants influences not only the local biological reactions but also affects at least the clinical result in orthopaedic application. During the last decades, strong efforts have been made to improve osteointegration and prevent bacterial adhesion to these surfaces. Following the rule of "smaller, faster, cheaper", nanotechnology has encountered clinical application. It is evident that the hierarchical implant surface micro- and nanotopography orchestrate the biological cascades of early peri-implant endosseous healing or implant loosening. This review of the literature gives a brief overview of nanostructured titanium-base biomaterials designed to improve osteointegration and prevent from bacterial infection. © 2017 by the authors.
    view abstract10.3390/ma10111302
  • Cartilage regeneration surgery on the hip: What is feasible? [Knorpelregenerative Eingriffe am Hüftgelenk: Was ist machbar?]
    Landgraeber, S. and Jäger, M. and Fickert, S.
    Orthopade 46 (2017)
    Localized cartilage defects at the hip are mainly caused by pre-arthritic deformities, particularly by cam-type femoroacetabular impingement (FAI). Timely elimination of symptomatic deformities can prevent further progression such as cartilage defects. As the defects mostly occur in the anterolateral part of the acetabulum, they can be easily treated either by open surgery or by arthroscopy. To date the most effective methods of treatment are bone marrow stimulation, with or without a covering of biomaterials, and autologous chondrocyte transplantation. In selected cases, readaptation of the damaged cartilage can be attempted by biological procedures. In the present article, the findings reported in current studies on these procedures are summarized and discussed in detail. An outlook is given regarding possible future treatment concepts. © 2017, Springer Medizin Verlag GmbH.
    view abstract10.1007/s00132-017-3491-6
  • Characteristics of elective hip replacement in the elderly
    Claßen, T. and Scheid, C. and Landgraeber, S. and Jäger, M.
    Orthopade 46 (2017)
    Due to demographic changes the number of elderly patients undergoing hip replacement surgery is increasing. In order to ensure safe treatment of elderly patients, age-specific medical factors must be taken into consideration. This article presents an overview of these factors. Furthermore, we evaluated our own patients treated between 2010 and 2015 regarding age-related treatment strategies and complication rates. Out of 3166 patients a total of 439 were over 80 years old (average age 84 years). It can be concluded from the scientific literature and from own data that elective hip replacement surgery in elderly patients is a technically safe procedure; however, the risk profile of each patient must be thoroughly analyzed so that in the event of even minor signs of potential complications countermeasures can be taken in good time. © 2016, Springer Medizin Verlag Berlin.
    view abstract10.1007/s00132-016-3364-4
  • Cost-effectiveness of timely versus delayed primary total hip replacement in Germany: A social health insurance perspective
    Mujica-Mota, R.E. and Watson, L.K. and Tarricone, R. and Jäger, M.
    Orthopedic Reviews 9 (2017)
    Without clinical guideline on the optimal timing for primary total hip replacement (THR), patients often receive the operation with delay. Delaying THR may negatively affect long-term health-related quality of life, but its economic effects are unclear. We evaluated the costs and health benefits of timely primary THR for functionally independent adult patients with end-stage osteoarthritis (OA) compared to non-surgical therapy followed by THR after progression to functional dependence (delayed THR), and non-surgical therapy alone (Medical Therapy), from a German Social Health Insurance (SHI) perspective. Data from hip arthroplasty registers and a systematic review of the published literature were used to populate a tunnel-state modified Markov lifetime model of OA treatment in Germany. A 5% annual discount rate was applied to costs (2013 prices) and health outcomes (Quality Adjusted Life Years, QALY). The expected future average cost of timely THR, delayed THR and medical therapy in women at age 55 were €27,474, €27,083 and €28,263, and QALYs were 20.7, 16.7, and 10.3, respectively. QALY differences were entirely due to health-related quality of life differences. The discounted cost per QALY gained by timely over delayed (median delay of 11 years) THR was €1270 and €1338 in women treated at age 55 and age 65, respectively, and slightly higher than this for men. Timely THR is cost-effective, generating large quality of life benefits for patients at low additional cost to the SHI. With declining healthcare budgets, research is needed to identify the characteristics of those able to benefit the most from timely THR. © R.E. Mujica-Mota et al., 2017.
    view abstract10.4081/or.2017.7161
  • Endoprostheses in the elderly: Biomaterials, implant selection and fixation technique
    Morlock, M.M. and Jäger, M.
    Orthopade 46 (2017)
    The replacement of hip and knee joints is one of the greatest success stories in orthopedics. Due to continuous improvement of biomaterials and implant design, patient-associated problems are now mostly multifactorial and only rarely caused by the implant. Abrasion was significantly reduced by the introduction of highly cross-linked polyethylene (PE), antioxidant stabilized PE, new ceramics and the development of ceramic and protective surfaces. It is assumed that further reduction of frictional resistance will not lead to a significantly better clinical result: however, the problem of periprosthetic infections and implant-related incompatibility is still unsolved and remains challenging for biomaterial research. For the knee joint PE will be irreplaceable for joint articulation even in the future due to the contact situation. Mobile bearings and fixed bearings are two established successful philosophies, which have shown comparably good clinical results. For the hip joint, it is forecasted that ceramic-on-ceramic will be the system of the future if the correct positioning and mounting of the components can be solved so that the problems, such as development of noise and breakage can be reduced to a minimum. An in-depth understanding and detailed knowledge of the biomaterials by the surgeon can prevent implant-related problems. For elderly patients it is assumed that the economic burden on the public healthcare system will have the strongest impact on implant selection. © 2016, Springer Medizin Verlag Berlin.
    view abstract10.1007/s00132-016-3361-7
  • Geometric analysis and clinical outcome of two cemented stems for primary total hip replacement with and without modular necks
    Haversath, M. and Wendelborn, C. and Jäger, M. and Schmidt, B. and Kowalczyk, W. and Landgraeber, S.
    Archives of Orthopaedic and Trauma Surgery 137 (2017)
    Introduction: Restoration of the physiological biomechanical principles of the hip is crucial in total hip replacement. The aim of this study was to compare an arthroplasty system with different offset options (a: Exeter®) with a dual-modular stem (b: Profemur Xm®). Materials and methods: A local and an inertial coordinate system were used to assist the description of the components’ assembly in the prosthesis. A resection line of the femoral head in standard position was added to the arthroplasties and geometric parameters were measured. The outcomes of 93 patients were clinically evaluated (a: n = 50, b: n = 43). Preoperative planning was compared to postoperative radiographs (femoral offset, leg-length), and clinical scores (HHS, WOMAC, total range of motion) were assessed preoperatively, and then 1 and 2 years after surgery. Results: The Exeter® offers an offset range from 32.1 to 56.9 mm and the Profemur Xm® a range from 29.3 to 55.3 mm. The leg-length variability of the Profemur Xm® has a range of 25.9 mm, the Exeter® a range of 13.7 mm. The Profemur Xm® offers more possible combinations of offset and leg-length reconstruction. The neck–stem angles of the Exeter® range from 125.2° to 126.3°, of the Profemur Xm® from 127.2° to 142.6°. There was no statistically significant difference in clinical outcome and radiological parameters. Conclusions: We conclude that both stems offer a wide range of options for anatomical reconstruction of the hip resulting in similarly good clinical results. The Profemur Xm® stem has advantages for the reconstruction of hips that deviate from standard anatomy but has the drawback of additional corrosive wear at the stem/neck interface. © 2017, Springer-Verlag GmbH Germany.
    view abstract10.1007/s00402-017-2785-9
  • Identification of hospitalized elderly patients at risk for adverse in-hospital outcomes in a university orthopedics and trauma surgery environment
    Gronewold, J. and Dahlmann, C. and Jäger, M. and Hermann, D.M.
    PLoS ONE 12 (2017)
    Background: As a consequence of demographic changes, hospitals are confronted with increasing numbers of elderly patients, who are at high risk of adverse events during hospitalization. Geriatric risk screening followed by comprehensive geriatric assessment (CGA) and treatment has been requested by geriatric societies and task forces to identify patients at risk. Since empirical evidence on factors predisposing to adverse hospital events is scarce, we now prospectively evaluated implications of geriatric risk screening followed by CGA in a university hospital department of orthopedics and trauma surgery. Methods: Three hundred and eighty-one patients 75 years admitted to the Department of Orthopedics and Trauma Surgery of the University Hospital Essen received Identification of Seniors at Risk (ISAR) Screening followed by CGA via a geriatric liaison service in case of positive screening results. Associations between ISAR, CGA, comorbid risk factors and diseases, length of hospital stay, number of nursing and physiotherapy hours, and falls during hospital stay were analyzed. Results: Of 381 ISAR screenings, 327 (85.8%) were positive, confirming a high percentage of patients at risk of adverse events. Of these, 300 CGAs revealed 82.7% abnormal results, indicating activities of daily living impairment combined with cognitive, emotional or mobility disturbances. Abnormal CGA resulted in a longer hospital stay (14.0±10.3 days in ISAR +/CGA abnormal compared with 7.6±7.0 days in ISAR+/CGA normal and 8.1±5.4 days in ISAR-, both p<0.001), increased nursing hours (3.4±1.1 hours/day in ISAR+/CGA abnormal compared with 2.5±1.0 hours/day in ISAR+/CGA normal and 2.2±0.8 hours/day in ISAR-, both p<0.001), and increased falls (7.3% in ISAR+/CGA abnormal, 0% in ISAR+/CGA normal, 1.9% in ISAR-). Physiotherapy hours were only significantly increased in ISAR +/CGA abnormal (3.0±2.7 hours) compared with in ISAR+/CGA normal (1.6±1.4 hours, p<0.001) whereas the comparison with ISAR- (2.4±2.4 hours) did not reach significance (p = 0.368). In multivariable regressions, the CGA domains activities of daily living impairment (assessed by Barthel-Index) and signs of depression (assessed by geriatric depression scale) predicted longer length of hospital stay. High ISAR score, and impairment in activities of daily living and cognition (assessed by mini-mental state examination and clock-drawing test) predicted increased nursing hours, and impairment in activities of daily living and mobility predicted increased physiotherapy hours. Conclusions: An abnormal geriatric screening and assessment is associated with longer hospital stay, more nursing and physiotherapy hours, and more falls. © 2017 Gronewold et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
    view abstract10.1371/journal.pone.0187801
  • Modifications to advanced Core decompression for treatment of Avascular necrosis of the femoral head
    Landgraeber, S. and Warwas, S. and Claßen, T. and Jäger, M.
    BMC Musculoskeletal Disorders 18 (2017)
    Background: "Advanced Core Decompression" (ACD) is a new technique for treatment of osteonecrosis of the femoral head (ONFH) that includes removal of the necrotic tissue using a percutaneous expandable reamer followed by refilling of the drill hole and the defect with an injectable, hard-setting, composite calcium sulphate (CaSO4)-calcium phosphate (CaPO4) bone graft substitute. As autologous bone has been shown to be superior to all other types of bone grafts, the aim of the study is to present and evaluate a modified technique of ACD with impaction of autologous bone derived from the femoral neck into the necrotic defect. Methods: A cohort of patients with an average follow-up of 30.06 months (minimum 12 months) was evaluated for potential collapse of the femoral head and any reasons that led to replacement of the operated hip. Only patients in stages 2a to 2c according to the Steinberg classification were included in the study. Results: In 75.9% the treatment was successful with no collapse of the femoral head or conversion to a total hip replacement. Analysis of the results of the different subgroups showed that the success rate was 100% for stage 2a lesions and 84.6% respectively 61.5% for stages 2b and 2c lesions. Conclusions: Previous studies with a comparable follow-up reported less favourable results for ACD without autologous bone. Especially in stages 2b and 2c the additional use of autologous bone has a positive effect. In comparison to other hip-preserving techniques, the modified ACD technique is a very promising and minimally invasive method for treatment of ONFH. Trial registration: German clinical trials register (DRKS00011269, retrospectively registered). © 2017 The Author(s).
    view abstract10.1186/s12891-017-1811-y
  • Relationship between GNAS1 T393C polymorphism and aseptic loosening after total hip arthroplasty
    Stelmach, P. and Kauther, M.D. and Fuest, L. and Kurscheid, G. and Gehrke, T. and Klenke, S. and Jäger, M. and Wedemeyer, C. and Bachmann, H.S.
    European Journal of Medical Research 22 (2017)
    Background: Aseptic loosening is a main cause for revision surgery after total hip arthroplasty (THA) and there is no reliable marker for the early detection of patients at high risk. This study has been performed to validate association of the T393C polymorphism (rs7121) in the GNAS1 gene, encoding for the alpha-subunit of heterotrimeric G-protein Gs, with risk for and time to aseptic loosening after THA, which has been demonstrated in our previous study. Methods: 231 patients with primary THA and 234 patients suffering from aseptic loosening were genotyped for dependency on GNAS1 genotypes and analyzed. Results: Genotyping revealed almost similar minor allele frequencies of 0.49 and 0.46, respectively. Consistently, genotype distributions of both groups were not significantly different (p = 0.572). Neither gender nor GNAS1 genotype showed a statistically significant association with time to loosening (p = 0.501 and p = 0.840). Stratification by gender, as performed in our previous study, was not able to show a significant genotype-dependent difference in time (female p = 0.313; male p = 0.584) as well as median time to aseptic loosening (female p = 0.353; male p = 0.868). Conclusion: This study was not able to confirm the results of our preliminary study. An association of the GNAS1 T393C polymorphisms with risk for and time to aseptic loosening after THA is unlikely. © 2017 The Author(s).
    view abstract10.1186/s40001-017-0271-z
  • Sex differences in the pro-inflammatory cytokine response to endotoxin unfold in vivo but not ex vivo in healthy humans
    Wegner, A. and Benson, S. and Rebernik, L. and Spreitzer, I. and Jäger, M. and Schedlowski, M. and Elsenbruch, S. and Engler, H.
    Innate Immunity 23 (2017)
    Clinical data indicate that inflammatory responses differ across sexes, but the mechanisms remain elusive. Herein, we assessed in vivo and ex vivo cytokine responses to bacterial endotoxin in healthy men and women to elucidate the role of systemic and cellular factors underlying sex differences in inflammatory responses. Participants received an i.v. injection of low-dose endotoxin (0.4 ng/kg body mass), and plasma TNF-α and IL-6 responses were analyzed over a period of 6 h. In parallel, ex vivo cytokine production was measured in endotoxin-stimulated blood samples obtained immediately before in vivo endotoxin administration. As glucocorticoids (GCs) play an important role in the negative feedback regulation of the inflammatory response, we additionally analyzed plasma cortisol concentrations and ex vivo GC sensitivity of cytokine production. Results revealed greater in vivo pro-inflammatory responses in women compared with men, with significantly higher increases in plasma TNF-α and IL-6 concentrations. In addition, the endotoxin-induced rise in plasma cortisol was more pronounced in women. In contrast, no sex differences in ex vivo cytokine production and GC sensitivity were observed. Together, these findings demonstrate major differences in in vivo and ex vivo responses to endotoxin and underscore the importance of systemic factors underlying sex differences in the inflammatory response. © SAGE Publications.
    view abstract10.1177/1753425917707026
  • Spondylodiscitis: Current strategies for diagnosis and treatment
    Michiels, I. and Jäger, M.
    Orthopade 46 (2017)
    Spondylodiscitis is a severe infectious disease of the intervertebral discs and of the adjacent parts of the vertebral bodies, culminating in destruction of the mobile segment. It is accompanied by a mortality rate of approximately 15%. Severe courses of the disease can also lead to abscess formation and dispersal of sepsis. Malpositioning of the axis organ and deficits in neurological function up to paraplegia are also possible complications. Timely diagnostics and targeted therapy contribute to minimizing the risk of significant health disorders. This review article gives a summary of important algorithms in the diagnostics and treatment and discusses them against the background of currently available literature. According to the current state of knowledge the surgical treatment of spondylodiscitis provides many advantages and is therefore the method choice, even if a conservative approach can be successful in selected cases. The endpoints of treatment are cleansing of the infection with normalization of laboratory parameters of inflammation and the osseous fusion of the mobile segment. © 2017, Springer Medizin Verlag GmbH.
    view abstract10.1007/s00132-017-3436-0
  • The double-transforaminal lumbar interbody fusion: An innovative one-stage surgical technique for posterior kyphosis correction
    Jäger, M. and Tassemeier, T.
    Orthopedic Reviews 9 (2017)
    Posttraumatic deformities after vertebral fractures are challenging for orthopedic surgeons in the non-operative and operative field. Especially osteoporotic fractures may cause a hyperkyphosis resulting in segmental or global sagittal imbalance and chronic back pain. Different vertebral osteotomies are potent to restore sagittal profile but show a very high perioperative risk including neurological and soft tissue complications. In addition, some of these extensive operations require a two-step procedure including posterior and anterior approaches. Therefore, these established techniques may be contraindicated in elderly or multimorbide patients suffering from concomitant diseases. The authors describe the double transforaminal lumbar interbody fusion (TLIF) osteotomy (DTO) as an innovative one-stage and low-invasive surgical technique to correct a fixed posttraumatic kyphosis in the thoracolumbar junction. The procedure includes posterior release (laminectomy, facettectomy, nucleotomy) complication rates, especially in ankylosing tran combined with two expandable TLIF implants (sandwich technique) and posterior instrumentation and is illustrated by a case of a multimorbide 78-year old female. © M. Jäger and T. Tassemeier, 2017.
    view abstract10.4081/or.2017.7107
  • Two-year follow-up after advanced core decompression
    Classen, T. and Warwas, S. and Jäger, M. and Landgraeber, S.
    Journal of Tissue Engineering and Regenerative Medicine 11 (2017)
    The so-called “Advanced Core Decompression” (ACD) is a new option that tries to remove the necrotic tissue in patients with osteonecrosis of the femoral head (AVN) in a minimally invasive way by the use of a percutaneous expandable reamer and refilling with a resorbable and osteoinductive bone-graft substitute. Seventy-two hips of sixty patients with a mean follow-up of 29.14 months after ACD have been included in this study. Patients underwent physical examination preoperatively and six weeks after surgery as well as at two further follow-ups. Certain phases in disease progression and size of the necrotic lesion were differentiated on the basis of the classification of osteonecrosis of the femoral head by Steinberg.The femoral heads had collapsed in 24 cases (33%). Analysis of the survival rates with regard to defect size revealed that the largest defects had a significantly higher rate of femoral head collapse than the smaller defects. Clinical scores were also depending on defect size but also on disease stage. The current ACD technique has not yet achieved any significant improvement in the success rate of core decompression procedures. It can be concluded that the success of ACD depends especially on the defect size. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    view abstract10.1002/term.2056
  • What older patients are worth
    Jäger, M.
    Orthopade 46 (2017)
    view abstract10.1007/s00132-016-3353-7
  • What older patients are worth [Was uns ältere Patienten wert sind]
    Jäger, M.
    Der Orthopade 46 (2017)
    view abstract10.1007/s00132-016-3353-7
  • A Single Dose of the Anti-Resorptive Peptide Human Calcitonin Paradoxically Augments Particle- and Endotoxin-Mediated Pro-Inflammatory Cytokine Production in Vitro
    Jablonski, H. and Wedemeyer, C. and Bachmann, H.S. and Schlagkamp, M. and Bernstein, A. and Jäger, M. and Kauther, M.D.
    Hormone and Metabolic Research 48 (2016)
    The peptide hormone calcitonin (CT) is known to inhibit bone resorption and has previously been shown also to prevent particle-induced osteolysis, the leading cause of revision arthroplasty. In the present study, the influence of human CT on the initial inflammatory response to particulate wear debris or bacterial endotoxins, ultimately leading to osteoclast-mediated bone resorption, was analysed in human THP-1 macrophage-like cells. The cells were activated with either ultra-high molecular weight polyethylene (UHMWPE) particles or bacterial lipopolysaccharides (LPS) in order to simulate an osteolysis-associated inflammatory response. The cells were simultaneously treated with human CT (10-9 M). Cytokine production of tumour necrosis factor (TNF)-α was quantified on both RNA and protein levels while interleukins (IL)-1β and IL-6 were measured as secreted protein only. Stimulation of the cells with either particles or LPS led to a dose- and time-dependent increase of TNF-α mRNA production and protein secretion of TNF-α, IL-1β, and IL-6. Application of CT mostly enhanced cytokine production as elicited by UHMWPE particles while a pronounced transient inhibitory effect on LPS-induced inflammation became evident at 24 h of incubation. Human CT displayed ambivalent effects on the wear- and LPS-induced production of pro-inflammatory cytokines. Thereby, the peptide primarily upregulated particle-induced inflammation while LPS-induced cytokine secretion was temporarily attenuated in a distinct manner. It needs to be evaluated whether the pro- or anti-inflammatory action of CT contributes to its known anti-resorptive effects. Thus, the therapeutic potential of the peptide in the treatment of either particle- or endotoxin-mediated bone resorption could be determined.
    view abstract10.1055/s-0042-108338
  • Antivenom therapy after a black mamba snakebite
    Schutzbach, M. and Vonderhagen, S. and Jäger, M.
    Unfallchirurg 119 (2016)
    A 24-year-old man was bitten on his right forefinger by his black mamba while he was feeding the animal. The primary symptoms caused by a full injection of the snake’s venom therefore presented a life-threating situation. Due to pre-hospital troubleshooting of the emergency medical service and the timely administration of the antivenom further potentially harmful effects caused by the snakes venom were avoided. © 2016, Springer-Verlag Berlin Heidelberg.
    view abstract10.1007/s00113-016-0241-x
  • Arthroscopic three-dimensional autologous chondrocyte transplantation using spheroids for the treatment of full-thickness cartilage defects of the hip joint
    Körsmeier, K. and Claßen, T. and Kamminga, M. and Rekowski, J. and Jäger, M. and Landgraeber, S.
    Knee Surgery, Sports Traumatology, Arthroscopy 24 (2016)
    Purpose: Treatment of full-thickness cartilage defects in the hip is a major issue for orthopaedic surgeons. Autologous matrix-induced three-dimensional chondrocyte transplantation using three-dimensional spheroids (ACT 3D) may be an option for treatment. The aim of the study is to describe the feasibility and first clinical results of ACT 3D with spheroids at the hip. Methods: In this report, the surgical technique was described for the first time, and the outcome of sixteen patients with chondral defects induced by cam-type femoroacetabular impingement (FAI) who were followed up in a prospective study was evaluated. All patients underwent physical examination before the first surgery and again before the second (about 6 weeks later). Further examinations were performed 6 weeks after the second surgery and at an average follow-up period of 16.09 months. At every visit, the non-arthritic hip score (NAHS) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) were obtained. In addition, patient satisfaction was evaluated during the last follow-up examination by means of a questionnaire. Results: The NAHS and WOMAC scores had significantly improved 6 weeks after arthroscopic treatment of the cam-type FAI, and a further significant enhancement was seen 6 weeks after the second surgery with application of the chondrocyte spheroids. In the last follow-up, the mean results were equally as good as the second follow-up examination 12 weeks after surgery. Conclusions: The present study shows that ACT 3D using spheroids is a feasible method that can be easily performed during arthroscopy. As the first results have been encouraging, the ACT 3D with spheroids at the hip should be continued. More studies should be initiated to get an impression of the quality grade of this method in comparison with other treatment options in case of chondral defects at the hip. Level of evidence: III. © 2014, European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).
    view abstract10.1007/s00167-014-3293-x
  • Backside Wear Analysis of Retrieved Acetabular Liners with a Press-Fit Locking Mechanism in Comparison to Wear Simulation in Vitro
    Reyna, A.L.P. and Jäger, M. and Floerkemeier, T. and Frecher, S. and Delank, K.-S. and Schilling, C. and Grupp, T.M.
    BioMed Research International 2016 (2016)
    Backside wear due to micromotion and poor conformity between the liner and its titanium alloy shell may contribute to the high rates of retroacetabular osteolysis and consequent aseptic loosening. The purpose of our study was to understand the wear process on the backside of polyethylene liners from two acetabular cup systems, whose locking mechanism is based on a press-fit cone in combination with a rough titanium conical inner surface on the fixation area. A direct comparison between in vitro wear simulator tests (equivalent to 3 years of use) and retrieved liners (average 13.1 months in situ) was done in order to evaluate the backside wear characteristics and behavior of these systems. Similar wear scores between in vitro tested and retrieved liners were observed. The results showed that this locking mechanism did not significantly produce wear marks at the backside of the polyethylene liners due to micromotion. In all the analyzed liners, the most common wear modes observed were small scratches at the cranial fixation zone directly below the rough titanium inner surface of the shell. It was concluded that most of the wear marks were produced during the insertion and removal of the liner, rather than during its time in situ. © 2016 Ana Laura Puente Reyna et al.
    view abstract10.1155/2016/8687131
  • Bone marrow aspirate concentrate in combination with intravenous iloprost increases bone healing in patients with avascular necrosis of the femoral head: A matched pair analysis
    Pilge, H. and Bittersohl, B. and Schneppendahl, J. and Hesper, T. and Zilkens, C. and Ruppert, M. and Krauspe, R. and Jäger, M.
    Orthopedic Reviews 8 (2016)
    With disease progression, avascular necrosis (AVN) of the femoral head may lead to a collapse of the articular surface. The exact pathophysiology of AVN remains unclear, although several conditions are known that can result in spontaneous cell death, leading to a reduction of trabecular bone and the development of AVN. Hip AVN treatment is stage-dependent in which two main stages of the disease can be distinguished: pre-collapse (ARCO 0-II) and post-collapse stage (ARCO III-IV, crescent sign). In the pre-collapse phase, core decompression (CD), with or without the addition of bone marrow (e.g. bone marrow aspirate concentrate, BMAC) or bone graft, is a common treatment alternative. In the postcollapse phase, THA (total hip arthroplasty) must be performed in most of the patients. In addition to surgical treatment, the intravenous application of Iloprost has been shown to have a curative potential and analgesic effect. From October 2009 to October 2014, 49 patients with AVN (stages I-III) were treated with core decompression at our institution. All patients were divided into group A (CD + BMAC) and group B (CD alone). Of these patients, 20 were included in a matched pair analysis. The patients were matched to age, gender, ARCO-stage, Kerboul combined necrotic angle, the cause of AVN, and whether Iloprost-therapy was performed. The Merle d’Aubigné Score and the Kerboul combined necrotic angle in a-p and lateral radiographs were evaluated pre- and postoperatively. The primary endpoint was a total hip arthroplasty. In group A, two patients needed THA while in group B four patients were treated with THA. In group A, the Merle d’Aubigné Score improved from 13.5 (pre-operatively) to 15.3 (postoperatively). In group B there was no difference between the pre- (14.3) and postoperative (14.1) assessment. The mean of the Kerboul angle showed no difference in both groups compared pre- to postoperatively (group A: pre-op 212°, postop 220°, group B: pre-op 213, postop 222°). Regarding radiographic evaluation, the interobserver variability revealed a moderate agreement between two raters regarding the pre- (ICC 0.594) and postoperative analysis (ICC 0.604).This study demonstrates that CD in combination with the application of autologous bone marrow aspirate concentrate into the femoral head seems to be a safe and efficient treatment alternative in the early stages of AVN of the femoral head when compared to CD alone. © 2016, Page Press Publications. All rights reserved.
    view abstract10.4081/or.2016.6902
  • Effect of the stiffness of bone substitutes on the biomechanical behaviour of femur for core decompression
    Tran, T.N. and Kowalczyk, W. and Hohn, H.P. and Jäger, M. and Landgraeber, S.
    Medical Engineering and Physics 38 (2016)
    Core decompression is the most common procedure for treatment of the early stages of osteonecrosis of the femoral head. The purpose of this study was to compare the biomechanical performance of four different bone graft substitutes combined with core decompression. Subject-specific finite element models generated from computed tomography (CT) scan data were used for a comprehensive analysis. Two different contact conditions were simulated representing states of osseointegration at the interface. Our results showed that the use of a low-stiffness bone substitute did not increase the risk of femoral fracture in the early postoperative phase, but resulted in less micromotion and interfacial stresses than high-stiffness bone substitutes. © 2016 IPEM
    view abstract10.1016/j.medengphy.2016.05.008
  • Human mesenchymal stromal/stem cells acquire immunostimulatory capacity upon cross-talk with natural killer cells and might improve the NK cell function of immunocompromised patients
    Cui, R. and Rekasi, H. and Hepner-Schefczyk, M. and Fessmann, K. and Petri, R.M. and Bruderek, K. and Brandau, S. and Jäger, M. and Flohé, S.B.
    Stem Cell Research and Therapy 7 (2016)
    Background: The suppressive effect of mesenchymal stromal/stem cells (MSCs) on diverse immune cells is well known, but it is unclear whether MSCs additionally possess immunostimulatory properties. We investigated the impact of human MSCs on the responsiveness of primary natural killer (NK) cells in terms of cytokine secretion. Methods: Human MSCs were generated from bone marrow and nasal mucosa. NK cells were isolated from peripheral blood of healthy volunteers or of immunocompromised patients after severe injury. NK cells were cultured with MSCs or with MSC-derived conditioned media in the absence or presence of IL-12 and IL-18. C-C chemokine receptor (CCR) 2, C-C chemokine ligand (CCL) 2, and the interferon (IFN)-γ receptor was blocked by specific inhibitors or antibodies. The synthesis of IFN-γ and CCL2 was determined. Results: In the absence of exogenous cytokines, trace amounts of NK cell-derived IFN-γ licensed MSCs for enhanced synthesis of CCL2. In turn, MSCs primed NK cells for increased release of IFN-γ in response to IL-12 and IL-18. Priming of NK cells by MSCs occurred in a cell-cell contact-independent manner and was impaired by inhibition of the CCR2, the receptor of CCL2, on NK cells. CD56bright NK cells expressed higher levels of CCR2 and were more sensitive to CCL2-mediated priming by MSCs and by recombinant CCR2 ligands than cytotoxic CD56dim NK cells. NK cells from severely injured patients were impaired in cytokine-induced IFN-γ synthesis. Co-culture with MSCs or with conditioned media from MSCs and MSC/NK cell co-cultures from healthy donors improved the IFN-γ production of the patients' NK cells in a CCR2-dependent manner. Conclusions: A positive feedback loop driven by NK cell-derived IFN-γ and MSC-derived CCL2 increases the inflammatory response of cytokine-stimulated NK cells not only from healthy donors but also from immunocompromised patients. Therapeutic application of MSCs or their soluble factors might thus improve the NK function after severe injury. © 2016 The Author(s).
    view abstract10.1186/s13287-016-0353-9
  • Ibandronate in stable renal transplant recipients with low bone mineral density on long-term follow-up
    Tillmann, F.P. and Schmitz, M. and Jäger, M. and Krauspe, R. and Rump, L.C.
    International Urology and Nephrology 48 (2016)
    Background: Bone mineral density (BMD) has been reported to increase without specific treatment in long-term renal transplant recipients. The aim of this study was to evaluate the effect of ibandronate on BMD and kidney function in long-term renal transplant recipients as compared to a control group. Furthermore, we searched for a gender-specific treatment effect of ibandronate on BMD. Methods: In a retrospective, matched case-control study 60 stable renal transplant recipients were included on long-term follow-up. The patient cohort was divided into two groups. The control group (n = 30) comprised patients with close-to-normal bone mineral density who did not receive ibandronate treatment and the treatment group (n = 30) comprised patients with reduced bone mineral density who received ibandronate treatment. The groups were matched for sex, age at the time of renal transplantation, use of steroids, renal transplant function and time lag between the dual-energy X-ray absorptiometry (DEXA) measurements and renal transplantation. Patients of the treatment group were treated with 12.0 ± 6.7 g ibandronate. Treatment cycles lasted 19.3 ± 11.0 months. The first bone mineral density testing was performed 55.3 ± 60.2 months after renal transplantation followed by a second measurement 26.8 ± 12.1 months later. Results: Both groups did not differ in absolute (g/cm2) or relative (%) changes in BMD at the lumbar spine (0.033 ± 0.079 vs. 0.055 ± 0.066 g/cm2, p = 0.217 and 3.6 ± 7.8 vs. 6.4 ± 8.1 %, p = 0.124) or femoral neck (0.013 ± 0.106 vs. 0.025 ± 0.077 g/cm2, p = 0.647 and 3.2 ± 13.6 vs. 5.0 ± 13.1 %, p = 0.544) over the study period. There was no correlation of ibandronate dosages with changes in BMD (LS: r = −0.089; p = 0.639 and FN: r =+0.288; p = 0.445). We could neither determine a negative effect of ibandronate on renal transplant function over the study period, estimated via the CKD-EPI formula (−2.9 ± 7.6 vs. −2.7 ± 10.6 mL/min/1.73 m2, p = 0.900) nor a gender-specific action of ibandronate on bone mass changes. Conclusions: Ibandronate treatment was safe with respect to renal transplant function but did not result in a significant additive improvement in bone mineral density as compared to the untreated control group. A gender-specific action of ibandronate on BMD at the LS or FN could not be determined either. © 2015, Springer Science+Business Media Dordrecht.
    view abstract10.1007/s11255-015-1133-7
  • Is early treatment of cam-type femoroacetabular impingement the key to avoiding associated full thickness isolated chondral defects?
    Claßen, T. and Körsmeier, K. and Kamminga, M. and Beck, S. and Rekowski, J. and Jäger, M. and Landgraeber, S.
    Knee Surgery, Sports Traumatology, Arthroscopy 24 (2016)
    Purpose: Hip arthroscopy is a safe and reproducible method for treating femoroacetabular impingement (FAI) and has evolved greatly in recent years. But little is known about the influences on the outcome after surgery. The aims of the current study were to elucidate (1) which parameters can be used as a marker for the presence of chondral and labral lesions, (2) the postoperative clinical outcome, and (3) at which time after surgery recovery occurs. Methods: A prospective study was performed with 177 patients who underwent hip arthroscopy because of cam-type FAI. The patients were examined preoperatively as well as 6 weeks and 6 months postoperatively, and their condition was rated according to the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and the Non-Arthritic Hip Score (NAHS). Statistical analyses were performed to evaluate the influence of independent factors such as “patient age,” “pain duration before surgery” on the clinical outcome, and the appearance of chondral or labral defects. Results: The NAHS and WOMAC scores showed a significant enhancement 6 weeks after surgery. Only the NAHS showed a further improvement after 6 months. A positive correlation with the dependent variable “chondral lesion” was evaluated for the independent variables “pain duration before surgery,” “preoperative NAHS,” and “labrum lesion”. Using ROC analysis, the optimal cutoff value of “pain duration before surgery” as a predictor was 9.5 months, for the NAHS 42.5 points. For the dependent variable, “6-month postoperative NAHS” significant correlations for the independent variables “age” and “pain duration before surgery” were revealed with a cutoff value of 55.5 years, respectively, 23.5 months. Conclusions: It was concluded from the results that the date of surgery is relevant for the appearance of chondral defects. Patient age is a further relevant factor for clinical outcome. Recovery after hip arthroscopy takes place mainly in the first 6 weeks after surgery. Level of evidence: Therapeutic study, Level III. © 2014, European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).
    view abstract10.1007/s00167-014-3332-7
  • Long-term clinical results after iloprost treatment for bone marrow edema and avascular necrosis
    Classen, T. and Becker, A. and Landgraeber, S. and Haversath, M. and Li, X. N. and Zilkens, C. and Krauspe, R. and Jager, M.
    Orthopedic Reviews 8 (2016)
    The treatments of avascular osteonecrosis (AVN) include both conservative and surgical methods which are dependent on the stage and progression of the disease. The vasoactive-prostaglandin-analogue iloprost (PGI2) has been utilized in several areas of medicine and recently has been used for the treatment of AVN. A total of 108 patients with 136 osteonecrosis of different joints, etiology and severity were treated with iloprost. The mean follow-up was 49.71 months: range 15-96 months, and outcome measurements recorded regarding subjective complaints, visual analog scale (pain), function and survival. The outcome scores used include the Harris Hip Score, Knee Society score, Foot and Ankle Survey, visual analogue scale (VAS) and a separate questionnaire. The location and etiology of AVN in our study demonstrated the typical pattern. All of the observed side effects of the therapy were minor and completely reversible. Most of patients (74.8%) showed a significant improvement of subjective complaints and decrease in VAS pain scores after the treatment with iloprost. However, 20% of the treated joints with the stadium Association for Research on Osseous Circulation (ARCO) grade 2, 71% with ARCO 3 and 100% with ARCO 4 underwent subsequent total joint replacement. The medical treatment of bone marrow edema or avascular osteonecrosis by Iloprost provides an safe and effective alternative strategy in the management of AVN presenting in the early stages (ARCO 1 or 2). For more advanced stages (ARCO 3 or 4), surgical intervention should be prioritized.
    view abstract10.4081/or.2016.6150
  • Necrotizing fasciitis – a clinical diagnosis
    Scheid, C. and Dudda, M. and Jäger, M.
    Orthopade 45 (2016)
    Necrotizing fasciitis is a life-threatening clinical pattern, which may lead to multi-organ failure and death with delayed diagnosis or inadequate treatment. We report on a 68-year old patient who developed necrotizing fasciitis of the right elbow with multiorgan failure and long-term ventilation after an accidental and minor injury. The patient survived as a result of an early diagnosis and surgical intervention. In this case report we want to clarify the diagnosis and treatment of necrotizing fasciitis and give an overview of the recent literature on the topic. © 2016, Springer-Verlag Berlin Heidelberg.
    view abstract10.1007/s00132-016-3318-x
  • Operative technique and clinical outcome in endoscopic core decompression of osteochondral lesions of the talus: A pilot study
    Beck, S. and Claßen, T. and Haversath, M. and Jäger, M. and Landgraeber, S.
    Medical Science Monitor 22 (2016)
    Background: Revitalizing the necrotic subchondral bone and preserving the intact cartilage layer by retrograde drilling is the preferred option for treatment of undetached osteochondral lesions of the talus (OLT). We assessed the effectiveness of Endoscopic Core Decompression (ECD) in treatment of OLT. Material/Methods: Seven patients with an undetached OLT of the medial talar dome underwent surgical treatment using an arthroscopically- guided transtalar drill meatus for core decompression of the lesion. Under endoscopic visualization the OLT was completely debrided while preserving the cartilage layer covering the defect. The drill tunnel and debrided OLT were filled using an injectable bone graft substitute. Various clinical scores, radiographic imaging, and MRI were evaluated after a mean follow-up of 24.1 months. Results: The American Orthopedic Foot and Ankle Society Score significantly improved from 71.0±2.4 to 90.3±5.9, and the Foot and Ankle Disability Index improved from 71.8±11.1 to 91.7±4.8. Radiographically, we observed good bone remodelling of the medial talar dome contour within 3 months. In MRI, an alteration of the bony signal of the drill tunnel and the excised OLT remained for more than 12 months. Conclusions: First follow-up results for the surgical technique described in this study are highly promising for treatment of undetached stable OLT grade II or transitional stage II-III according to the Pritsch classification. Even lesions larger than 150 mm2 showed good clinical scores, with full restoration of the medial talar dome contour in radiographic imaging. © Med Sci Monit, 2016.
    view abstract10.12659/MSM.896522
  • Osteogenic differentiation and proliferation of bone marrow-derived mesenchymal stromal cells on PDLLA + BMP-2-coated titanium alloy surfaces
    Haversath, M. and Hülsen, T. and Böge, C. and Tassemeier, T. and Landgraeber, S. and Herten, M. and Warwas, S. and Krauspe, R. and Jäger, M.
    Journal of Biomedical Materials Research - Part A 104 (2016)
    RhBMP-2 is clinically applied to enhance bone healing and used in combination with titanium fixation implants. The purpose of this in vitro study was to compare the osteogenic differentiation and proliferation of hMSC on native polished versus sandblasted titanium surfaces (TS) and to test their behavior on pure poly-D,L-lactide (PDLLA) coated as well as PDLLA + rhBMP-2 coated TS. Furthermore, the release kinetics of PDLLA + rhBMP-2-coated TS was investigated. Human bone marrow cells were obtained from three different donors (A: male, 16 yrs; B: male, 27 yrs, C: male, 49 yrs) followed by density gradient centrifugation and flow cytometry with defined antigens. The cells were seeded on native polished and sandblasted TS, PDLLA-coated TS and PDLLA + rhBMP-2-coated TS. Osteogenic differentiation (ALP specific activity via ALP and BCA assay) and proliferation (LDH cytotoxicity assay) was examined on day 7 and 14 and release kinetics of rhBMP-2 was investigated on day 3, 7, 10, and 14. We found significant higher ALP specific activity and LDH activity on native polished compared to native sandblasted surfaces. PDLLA led to decreased ALP specific and LDH activity on both surface finishes. Additional rhBMP-2 slightly diminished this effect. RhBMP-2-release from coated TS decreased nearly exponentially with highest concentrations at the beginning of the cultivation period. The results of this in vitro study suggest that native TS stimulate hMSC significantly stronger toward osteogenic differentiation and proliferation than rhBMP-2 + PDLLA-layered TS in the first 14 days of cultivation. The PDLLA-layer seems to inhibit local hMSC differentiation and proliferation. © 2015 Wiley Periodicals, Inc.
    view abstract10.1002/jbm.a.35550
  • S3-Guideline non-traumatic adult femoral head necrosis
    Roth, A. and Beckmann, J. and Bohndorf, K. and Fischer, A. and Heiß, C. and Kenn, W. and Jäger, M. and Maus, U. and Nöth, U. and Peters, K.M. and Rader, C. and Reppenhagen, S. and Smolenski, U. and Tingart, M. and Kopp, I. and Sirotin, I. and Breusch, S.J.
    Archives of Orthopaedic and Trauma Surgery 136 (2016)
    Introduction: The treatment of adult non-traumatic avascular necrosis of the femoral head (AVN; N-ANFH) within an estimated incidence of 5000–7000 cases per annum in Germany remains a challenge. Risk factors include steroids, alcohol abuse, chemotherapy and immunosuppressive medication, but a genetic predisposition has been suggested. Early diagnosis of this often bilateral disease process is essential for successful conservative or joint preserving surgical management. In this review, we present the update German consensus S3 guideline “diagnosis and management for N-ANFH” as a concise summary. Materials and methods: This systematic review is based on the published literature from January 1, 1970 to April 31, 2013 (German and English language). Inclusion criteria were systematic reviews, meta-analyses and relevant peer review publications. We identified a total of 3715 related publications, of which 422 were suitable according to the SIGN criteria, but only 159 fulfilled our inclusion criteria. Results and conclusions: Clinical suspicion of N-ANFH mandates radiographic evaluation. If radiographs are normal MRI scans are recommended, which should be evaluated according to the ARCO-classification. Differential diagnoses include transient osteoporosis, bone bruise, insufficiency fracture and destructive arthropathy. Untreated, subchondral fractures commonly occur within 2 years, during which the risk for contralateral involvement is high—thereafter unlikely. Conservative management with Ilomedin and Alendronat can be tried, but other pharmacological or physical treatments are inappropriate. No specific joint preserving procedure can be recommended, but core decompression should be considered in early stages if necrosis is <30 %. In ARCO stages IIIc or IV total hip arthroplasty (THA) should be contemplated, which offers similar outcome compared to osteoarthritis. Young age is the main risk factor for higher revision rates after THA for N-ANFH. © 2015, Springer-Verlag Berlin Heidelberg.
    view abstract10.1007/s00402-015-2375-7
  • The BCL2-938C>A promoter polymorphism is associated with risk for and time to aseptic loosening of total hip arthroplasty
    Stelmach, P. and Wedemeyer, C. and Fuest, L. and Kurscheid, G. and Gehrke, T. and Klenke, S. and Jäger, M. and Kauther, M.D. and Bachmann, H.S.
    PLoS ONE 11 (2016)
    Aseptic loosening is a major cause of revision surgery of total hip arthroplasty (THA). Only few host factors affecting aseptic loosening have been identified until now, although they are urgently needed to identify and possibly treat those patients at higher risk for aseptic loosening. To determine whether the functional single nucleotide polymorphism (SNP) c.-938C>A (rs2279115), located in the promoter region of the BCL2 gene has an impact on aseptic loosening of THA we genotyped and analyzed 234 patients suffering from aseptic loosening and 231 patients after primary THA. The polymorphism is associated with risk for aseptic loosening with the CC genotype at highest risk for aseptic loosening, Odds Ratio CC vs. AA 1.93, 95%CI 1.15-3.25, p = 0.013. In contrast, low risk AA genotype carriers that still developed aseptic loosening showed a significantly shorter time to aseptic loosening than patients carrying the C allele (p = 0.004). These results indicate that the BCL2-938C>A polymorphism influences the occurrence and course of aseptic loosening and suggests this polymorphism as an interesting candidate for prospective studies and analyses in THA registers. © 2016 Stelmach et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
    view abstract10.1371/journal.pone.0149528
  • The influence of calcitonin gene-related peptide on markers of bone metabolism in MG-63 osteoblast-like cells co-cultured with THP-1 macrophage-like cells under virtually osteolytic conditions
    Jablonski, H. and Rekasi, H. and Jäger, M.
    BMC Musculoskeletal Disorders 17 (2016)
    Background: The neuropeptide calcitonin gene-related peptide (CGRP) has been described to have an inhibitory effect on endotoxin- and wear particle-induced inflammation in the early stages of periprosthetic osteolysis. In the present study, the crosstalk between immune cells and osteoblasts in osteolytic conditions treated with CGRP has been analyzed to evaluate whether the anti-inflammatory properties of the peptide also have a beneficial, i.e. an anti-resorptive and osteo-anabolic impact on bone metabolism. Methods: MG-63 osteoblast-like cells were co-cultured with THP-1 macrophage-like cells stimulated with either ultra-high molecular weight polyethylene (UHMWPE) particles or different concentrations of bacterial lipopolysaccharides (LPS) and simultaneously treated with CGRP. Inflammation was monitored in terms of measuring the levels of tumor necrosis factor (TNF)-α secretion. Furthermore, the production of the osteoblast markers osteoprotegerin (OPG), receptor activator of nuclear factor κB ligand (RANKL), alkaline phosphatase (ALP) and osteopontin (OPN) was quantified. Also, ALP enzymatic activity was measured. Results: Stimulation of co-cultured THP-1 macrophages with either high levels of LPS or UHMWPE induced the secretion of TNF-α which could be inhibited by CGRP to a great extent. However, no remarkable changes in the OPG/RANKL ratio or bone ALP activity were observed. Interestingly, OPN was exclusively produced by THP-1 cells, thus acting as a marker of inflammation. In addition, TNF-α production in THP-1 single cell cultures was found to be considerably higher than in co-cultured cells. Conclusions: In the co-culture system used in the present study, no obvious relation between inflammation, its mitigation by CGRP, and the modulation of bone metabolism became evident. Nonetheless, the results suggest that during the onset of periprosthetic osteolysis the focus might lie on the modulation of inflammatory reactions. Possibly, implant-related inflammation might merely have an impact on osteoclast differentiation rather than on the regulation of osteoblast activity. © 2016 Jablonski et al.
    view abstract10.1186/s12891-016-1044-5
  • The intraarticular osteoid osteoma: A diagnostic and therapeutic challenge
    Husen, M. and Hövel, M. and Jäger, M.
    Orthopade 45 (2016)
    Intra- and, respectively, periarticular osteoid osteoma are accompanied by sympathical arthritis which itself can irreversibly destroy the cartilage of the joint. In contrast to other locations, intra- and periarticular osteoid osteoma are rare. Reactive and symptomatic accompanying arthritis may lead to irreversible cartilage destruction especially in chronic courses. Therefore early diagnosis and therapy is crucial. We present a case report and discuss these rare tumors by reviewing the literature. © 2016, Springer-Verlag Berlin Heidelberg.
    view abstract10.1007/s00132-015-3220-y
  • 3 Tesla high-resolution and delayed gadolinium enhanced MR imaging of cartilage (dGEMRIC) after autologous chondrocyte transplantation in the hip
    Lazik, A. and Körsmeier, K. and Claßen, T. and Jäger, M. and Kamminga, M. and Kraff, O. and Lauenstein, T.C. and Theysohn, J.M. and Landgraeber, S.
    Journal of Magnetic Resonance Imaging 42 (2015)
    Background To evaluate the feasibility of 3 Tesla (T) high-resolution and gadolinium enhanced MRI of cartilage (dGEMRIC) in the thin and rounded hip cartilage of patients after acetabular matrix-based autologous chondrocyte transplantation (MACT). Methods Under general ethics approval, 24 patients were prospectively examined 6-31 months after acetabular MACT at 3T using high-resolution proton-density weighted (PDw) images (bilateral PD SPACE, 0.8 mm isotropic; unilateral PD-TSE coronal/sagittal, 0.8 × 0.8 resp. 0.5 × 0.5 × 2.5 mm) as well as T1 mapping (3D-FLASH, 0.78 mm isotropic) in dGEMRIC technique, and clinically scored. The cartilage transplant was evaluated using an adapted MOCART score (maximum 85 points). T1 relaxation times were measured independently by two radiologists. Here, regions of interest were placed manually in automatically calculated relaxation-maps, both in the transplant and adjacent healthy cartilage regions. Interobserver reliability was estimated by means of intraclass-correlation (ICC). Results The transplant was morphologically definable in the PDw images of 23 patients with a mean MOCART score of 69 points (60-80 points, SD 6.5). T1 maps showed a clear differentiation between acetabular and femoral cartilage, but correlation with PDw images was necessary to identify the transplant. Mean T1 relaxation times of the transplant were 616.3 ms (observer 1) resp. 610.1 ms (observer 2), and of adjacent healthy acetabular cartilage 574.5 ms (observer 1) resp. 604.9 ms (observer 2). Interobserver reliability of the relaxation times in the transplant was excellent (ICC-coefficient 0.88) and in adjacent healthy regions good (0.77). Conclusion High-resolution PDw imaging with adapted MOCART scoring and dGEMRIC is feasible after MACT in the thin and rounded hip cartilage. J. Magn. Reson. Imaging 2015;42:624-633. © 2014 Wiley Periodicals, Inc.
    view abstract10.1002/jmri.24821
  • Calcitonin gene-related peptide modulates the production of pro-inflammatory cytokines associated with periprosthetic osteolysis by THP-1 macrophage-like cells
    Jablonski, H. and Kauther, M.D. and Bachmann, H.S. and Jäger, M. and Wedemeyer, C.
    NeuroImmunoModulation 22 (2015)
    Objective: An anti-resorptive impact of the neuropeptide calcitonin gene-related peptide (CGRP) on periprosthetic osteolysis, the leading cause of early prosthesis loosening, has been shown previously. In this study, the impact of CGRP on pro-inflammatory cytokine production associated with periprosthetic osteolysis was analysed using THP-1 macrophage-like cells. Methods: Cells were stimulated with ultra-high-molecular-weight polyethylene (UHMWPE) particles (cell-to-particle ratios of 1:100 and 1:500) and lipopolysaccharides (LPS; 1 μg/ml) to establish osteolytic conditions, and simultaneously treated with CGRP (10-8M). Receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL) and tumour necrosis factor (TNF)-α mRNA expression were measured by quantitative RT-PCR. RANK protein was detected by Western blot. Secreted protein levels of TNF-α as well as interleukin (IL)-1β and IL-6 were quantified in cell culture supernatants by ELISA and Bio-Plex cytokine assay, respectively. Results: Activation of macrophage-like cells failed to enhance the production of RANK but led to a dose- and time-dependent increase of TNF-α mRNA and secreted protein levels of TNF-α, IL-1β and IL-6. Application of CGRP time-dependently suppressed TNF-α mRNA expression induced by low-particle concentrations and LPS, while both particle- and LPS-induced secretion of TNF-α was inhibited. A pronounced inhibitory effect of CGRP on LPS-induced cytokine production at 24 h of incubation was also observed with IL-1β and IL-6. Conclusions: CGRP shows a time-dependent inhibitory effect on the secretion of osteolysis-associated pro-inflammatory cytokines, indicating an indirect anti-resorptive influence of the neuropeptide on both aseptic prosthesis loosening and bacterially induced bone resorption which might enhance the life time of total joint replacements. © 2014 S. Karger AG, Basel.
    view abstract10.1159/000360988
  • Geometric analysis of an expandable reamer for treatment of avascular necrosis of the femoral head
    Landgraeber, S. and Tran, T.N. and Claßen, T. and Warwas, S. and Theysohn, J. and Lazik, A. and Jäger, M. and Kowalczyk, W.
    Archives of Orthopaedic and Trauma Surgery 135 (2015)
    “Advanced core decompression” (ACD) is a treatment option for osteonecrosis of the femoral head (ONFH) that aims at complete removal of the necrotic tissue using a percutaneous expandable reamer and refilling of the head with an osteoconductive bone-graft substitute. The objective of this study was to evaluate if the success of ACD depends on the amount of necrotic tissue remaining after the procedure and how efficiently the necrotic tissue can be removed with the current reamer. Three-dimensional models of proximal femora including ONFH were generated from the preoperative MRIs of 50 patients who underwent ACD. Best-case removal was calculated by geometrical analysis. In 28 of 50 cases, postoperative MRI was used to determine how much necrotic tissue had been removed. Prognostic values and correlations were evaluated in order to assess success or failure of the treatment. The amount of preoperative and remaining necrosis correlates significantly with treatment failure. The larger both volumes are, the more likely it is that treatment will fail. In patients with remaining necrosis of less than 1000 mm3, no treatment failure was observed. The amount of necrosis actually removed differed significantly from the amount calculated as the best possible result. Simulation of the removal procedure showed that complete removal is not possible. These results led to the conclusion that the success of ACD depends on the amount of necrotic tissue remaining in the femoral head after the procedure. Modifications to the instrument are necessary to increase the amount of necrotic tissue that can be removed. © 2015, Springer-Verlag Berlin Heidelberg.
    view abstract10.1007/s00402-015-2287-6
  • Inflammation-induced pain sensitization in men and women: does sex matter in experimental endotoxemia?
    Wegner, A. and Elsenbruch, S. and Rebernik, L. and Roderigo, T. and Engelbrecht, E. and Jager, M. and Engler, H. and Schedlowski, M. and Benson, S.
    Pain 156 (2015)
    A role of the innate immune system is increasingly recognized as a mechanism contributing to pain sensitization. Experimental administration of the bacterial endotoxin lipopolysaccharide (LPS) constitutes a model to study inflammation-induced pain sensitization, but all existing human evidence comes from male participants. We assessed visceral and musculoskeletal pain sensitivity after low-dose LPS administration in healthy men and women to test the hypothesis that women show greater LPS-induced hyperalgesia compared with men. In this randomized, double-blind, placebo-controlled crossover study, healthy men (n = 20) and healthy women using oral contraceptives (n = 20) received an intravenous injection of 0.4 ng/kg body weight LPS or placebo. Pain sensitivity was assessed with established visceral and musculoskeletal pain models (ie, rectal pain thresholds; pressure pain thresholds for different muscle groups), together with a heartbeat perception (interoceptive accuracy) task. Plasma cytokines (tumor necrosis factor-a and interleukin-6) were measured along with state anxiety at baseline and up to 6-hour postinjection. Lipopolysaccharide application led to significant increases in plasma cytokines and state anxiety and decreased interoceptive awareness in men and women (P < 0.001, condition effects), with more pronounced LPS-induced cytokine increases in women (P < 0.05, interaction effects). Although both rectal and pressure pain thresholds were significantly decreased in the LPS condition (all P < 0.05, condition effect), no sex differences in endotoxin-induced sensitization were observed. In summary, LPS-induced systemic immune activation leads to visceral and musculoskeletal hyperalgesia, irrespective of biological sex. These findings support the broad applicability of experimental endotoxin administration as a translational preclinical model of inflammation-induced pain sensitization in both sexes.
    view abstract10.1097/j.pain.0000000000000256
  • S3 GuidelinePart 1: Diagnosis and Differential Diagnosis of Non-Traumatic Adult Femoral Head Necrosis
    Bohndorf, K. and Beckmann, J. and Jäger, M. and Kenn, W. and Maus, U. and Nöth, U. and Peters, K.M. and Rader, C. and Reppenhagen, S. and Roth, A.
    Zeitschrift fur Orthopadie und Unfallchirurgie 153 (2015)
    Non-traumatic femoral head necrosis (FHN) is primarily a disease of the middle-aged adult. Early diagnosis, at a time with lacking or minimal clinical symptoms, is mandatory to consider conservative therapy or joint preserving operations as a therapeutic option. The new German S3 guideline about diagnosis and therapy of FHN is a cooperative effort of five professional medical societies, overall headed by the Deutsche Gesellschaft für Orthopädie und Orthopädische Chirurgie (DGOOC). This review (part I/III) cites and explains the statements of the S3 guideline as agreed on the use of imaging methods for diagnosis of FHN. A diagnostic algorithm is presented. FHN clinically has to be considered in case of equivocal pain of a hip joint with a minimum of 6 weeks duration, when risk factors can be revealed, groin pain at clinical investigation, limping, pain or limitation of movement in case of load, and no obvious differential diagnoses. Is an FHN clinically suspected, primarily radiographs of the pelvis ap and a Lauenstein projection of the hip involved should be carried out. When the radiographs are normal, an MRI of the hips should follow routinely. MRI allows the diagnosis of FNH with high accuracy. Furthermore, MRI reveals the site and the size of the necrotic area involved and evaluates the integrity of the joint surface and subchondral fractures. When ARCO stage II (ARCO: Association Research Circulation Osseous) is diagnosed and MRI does not allow one to determine the joint surface with certainty, a CT of the hip joints should be performed. The S3 guideline explains and recommends the use of the ARCO classification. Although, this classification of 1993 is still largely based on radiographs, the pragmatic use of an extended version seems reasonable. Today, classical radiographic criteria like impression of the joint surface and subchondral fractures (crescent sign) are better to be evaluated by MRI, in cases of subtle findings MRI is even surpassed by CT. The extent of the necrosis in the femoral head as well as the size of the surface area involved is best revealed with MRI. Additionally, in the era of cross sectional imaging a stage 0 seems obsolete. The guideline also addresses practically important considerations about the differential diagnosis of misleading MRI findings. This especially holds true for bone marrow oedema in the femoral head which may be misinterpreted. The differentiating features between FHN, transient bone marrow oedema and destructive arthropathy are discussed. ©2015 Georg Thieme Verlag KG Stuttgart ·New York.
    view abstract10.1055/s-0035-1545901
  • S3 guidelinePart 2: Non-Traumatic Avascular Femoral Head Necrosis in Adults - Untreated Course and Conservative Treatment
    Roth, A. and Beckmann, J. and Smolenski, U. and Fischer, A. and Jäger, M. and Tingart, M. and Rader, C. and Peters, K.M. and Reppenhagen, S. and Nöth, U. and Heiss, C. and Maus, U.
    Zeitschrift fur Orthopadie und Unfallchirurgie 153 (2015)
    Background: In Germany there are 5000 to 7000 new cases of atraumatic avascular necrosis of the femoral head in adults per year. It occurs mostly in middle age. An increased frequency of idiopathic cases can be observed. Chemotherapy, corticoids and kidney transplants are frequently associated with the disease. In most cases the disease occurs on both sides. Early diagnosis is of particular importance, since in early stages it is most likely to avoid late damage with joint destruction. Whereas previously the temporary operational joint preservation and subsequent joint replacement were often the only option of treatment, conservative and joint-preserving measures today play an increasing role. Material and Methods: After the AWMF guidelines for S3 guideline clinical questions were formulated. Over the period from 01/01/1970 to 31/05/2013 a literature search was conducted. Systematic reviews, metaanalyses, original papers and clinical trials of all designs were evaluated. There were a total of 3715 references, of which 422 for the assessment regarding SIGN were eligible and finally 180 were in accord with the defined inclusion and exclusion criteria. For the untreated course and the assessment of conservative measures, a total of 42 references was suitable. In formulating the recommendations the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system was used, which distinguishes A shall, B should and 0 can. Results and Conclusion: If left untreated, the aFKN within 2 years leads to a subchondral fracture and subsequent collapse. After the diagnosis of femoral head necrosis, the risk of a disease of the opposite side is high within the next 2 years, then unlikely. The sole conservative treatment brings no benefit for the treatment of atraumatic avascular necrosis in the adult. Although it improves function, less pain can be obtained, and surgical intervention can be delayed, the progression is not stopped. Conservative treatment must therefore always be part of the overall treatment. In ARCO stage I to II Iloprost may be considered as a pharmacological approach to reduce the pain and the bone marrow oedema. This also applies to alendronate. Since this is an off-label use, and thus a therapeutic trial, an appropriate patient education must take place. For the use of anticoagulants and statins, there is no recommendation. Also the hyperbaric oxygen therapy, shock waves and pulsating electromagnetic fields or electrical stimulation cannot be recommended. © Georg Thieme Verlag KG Stuttgart New York.
    view abstract10.1055/s-0035-1545903
  • S3 GuidelinePart 3: Non-Traumatic Avascular Necrosis in Adults - Surgical Treatment of Atraumatic Avascular Femoral Head Necrosis in Adults
    Maus, U. and Roth, A. and Tingart, M. and Rader, C. and Jäger, M. and Nöth, U. and Reppenhagen, S. and Heiss, C. and Beckmann, J.
    Zeitschrift fur Orthopadie und Unfallchirurgie 153 (2015)
    The present article describes the guidelines for the surgical treatment of atraumatic avascular necrosis (aFKN). These include joint preserving and joint replacement procedures. As part of the targeted literature, 43 publications were included and evaluated to assess the surgical treatment. According to the GRADE and SIGN criteria level of evidence (LoE), grade of recommendation (EC) and expert consensus (EK) were listed for each statement and question. The analysed studies have shown that up to ARCO stage III, joint-preserving surgery can be performed. A particular joint-preserving surgery currently cannot be recommended as preferred method. The selection of the method depends on the extent of necrosis. Core decompression performed in stage ARCO I (reversible early stage) or stage ARCO II (irreversible early stage) with medial or central necrosis with an area of less than 30 % of the femoral head shows better results than conservative therapy. In ARCO stage III with infraction of the femoral head, the core decompression can be used for a short-term pain relief. For ARCO stage IIIC or stage IV core decompression should not be performed. In these cases, the indication for implantation of a total hip replacement should be checked. Additional therapeutic procedures (e.g., osteotomies) and innovative treatment options (advanced core decompression, autologous bone marrow, bone grafting, etc.) can be discussed in the individual case. In elective hip replacement complications and revision rates have been clearly declining for decades. In the case of an underlying aFKN, however, previous joint-preserving surgery (osteotomies and grafts in particular) can complicate the implantation of a THA significantly. However, the implant life seems to be dependent on the aetiology. Higher revision rates for avascular necrosis are particularly expected in sickle cell disease, Gaucher disease, or kidney transplantation patients. Furthermore, the relatively young age of the patient with avascular necrosis should be seen as the main risk factor for higher revision rate. The results after resurfacing (today with known restricted indications) and cemented as well as cementless THA in aFKN are comparable for the appropriate indication to those in coxarthrosis or other diagnoses. Regardless of the underlying disease endoprosthetic treatment in aFKN leads to good results. Both cemented and cementless fixation techniques can be recommended. © Georg Thieme Verlag KG Stuttgart New York.
    view abstract10.1055/s-0035-1545902
  • The role of calcitonin receptor signalling in polyethylene particle-induced osteolysis
    Neuerburg, C. and Wedemeyer, C. and Goedel, J. and Schlepper, R. and Hilken, G. and Schwindenhammer, B. and Schilling, A.F. and Jäger, M. and Kauther, M.D.
    Acta Biomaterialia 14 (2015)
    The detection of peptides from the calcitonin (CT) family in the periarticular tissue of loosened implants has raised hopes of opening new regenerative therapies in the process of aseptic loosening, which remains the major cause of early implant failure in endoprosthetic surgery. We have previously shown the roles of α-calcitonin gene-related peptide (α-CGRP) and the CALCA gene which encodes α-CGRP/CT in this process. To uncover the role of direct calcitonin receptor (CTR) mediated signalling, we studied particle-induced osteolysis (PIO) in a murine calvaria model with a global deletion of the CTR (CTR-KO) using μCT analysis and histomorphometry. As expected, CTR-KO mice revealed reduced bone volume compared to wild-type (WT) controls (p < 0.05). In CTR-KO mice we found significantly higher RANKL (receptor activator of NF-κB ligand) expression in the particle group than in the control group. The increase in osteoclast numbers by the particles was twice as high as the increase of osteoclasts in the WT mice (400 vs. 200%). Changes in the eroded surface and actual osteolysis due to ultrahigh-molecular-weight polyethylene particles were similar in WTs and CTR-KOs. Taken together, our findings strengthen the relevance of the OPG/RANK/RANKL system in the PIO process. CTR seems to have an effect on osteoclast differentiation in this context. As there were no obvious changes of the amount of PIO in CTR deficiency, regenerative strategies in aseptic loosening of endoprosthetic implants based on peptides arising from the CT family should rather focus on the impact of α-CGRP. © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
    view abstract10.1016/j.actbio.2014.11.051
  • Adiponectin attenuates osteolysis in aseptic loosening of total hip replacements
    Landgraeber, S. and Putz, S. and Schlattjan, M. and Bechmann, L.P. and Totsch, M. and Grabellus, F. and Hilken, G. and Jäger, M. and Canbay, A.
    Acta Biomaterialia 10 (2014)
    Joint replacements have a longer durability in patients with high serum levels of adiponectin (APN) than in patients with low levels. We aimed to characterize the unknown pathophysiological effects of APN on wear particle-induced inflammation, apoptosis and osteolysis. Immunohistochemistry was performed to detect APN, its receptors and apoptosis in patients with and without aseptic loosening. Additionally, APN knockout mouse studies and pharmacological intervention of APN were performed in an established calvarial mouse model. Osteolysis and inflammation were quantified by histomorphometry and microcomputed tomography, apoptosis by immunohistochemistry and TUNEL assay. In a cell culture model, human monocyte-derived macrophages were incubated with or without metal wear debris particles and partially treated with APN. Expression of APN, AdipoR1 and calreticulin in specimens from patients with aseptic loosening were significantly higher than in patients without aseptic loosening. Administration of APN in mice significantly reduced wear particle-induced inflammation, osteolysis and the number of caspase-3-positive macrophages. The cell culture model showed that APN leads to significantly lower values of TNF-α. These findings support a prominent role of APN in the development of particle-induced osteolysis and APN may be therapeutically useful in patients with aseptic loosening. © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
    view abstract10.1016/j.actbio.2013.08.031
  • Biotribology of a vitamin E-stabilized polyethylene for hip arthroplasty - Influence of artificial ageing and third-body particles on wear
    Grupp, T.M. and Holderied, M. and Mulliez, M.A. and Streller, R. and Jäger, M. and Blömer, W. and Utzschneider, S.
    Acta Biomaterialia 10 (2014)
    The objective of our study was to evaluate the influence of prolonged artificial ageing on oxidation resistance and the subsequent wear behaviour of vitamin E-stabilized, in comparison to standard and highly cross-linked remelted polyethylene (XLPE), and the degradation effect of third-body particles on highly cross-linked remelted polyethylene inlays in total hip arthroplasty. Hip wear simulation was performed with three different polyethylene inlay materials (standard: γ-irradiation 30 kGy, N2; highly cross-linked and remelted: γ-irradiation 75 kGy, EO; highly cross-linked and vitamin E (0.1%) blended: electron beam 80 kGy, EO) machined from GUR 1020 in articulation with ceramic and cobalt-chromium heads. All polyethylene inserts beneath the virgin references were subjected to prolonged artificial ageing (70 °C, pure oxygen at 5 bar) with a duration of 2, 4, 5 or 6 weeks. In conclusion, after 2 weeks of artificial ageing, standard polyethylene shows substantially increased wear due to oxidative degradation, whereas highly cross-linked remelted polyethylene has a higher oxidation resistance. However, after enhanced artificial ageing for 5 weeks, remelted XLPE also starts oxidate, in correlation with increased wear. Vitamin E-stabilized polyethylene is effective in preventing oxidation after irradiation cross-linking even under prolonged artificial ageing for up to 6 weeks, resulting in a constant wear behaviour. © 2014 Published by Elsevier Ltd. on behalf of Acta Materialia Inc.
    view abstract10.1016/j.actbio.2014.02.052
  • Direct comparison of intra-articular versus intravenous delayed gadolinium-enhanced MRI of hip joint cartilage
    Zilkens, C. and Miese, F. and Kim, Y.-J. and Jäger, M. and Mamisch, T.C. and Hosalkar, H. and Antoch, G. and Krauspe, R. and Bittersohl, B.
    Journal of Magnetic Resonance Imaging 39 (2014)
    Purpose To investigate the potential of delayed gadolinium-enhanced magnetic resonance imaging in cartilage (dGEMRIC) after intra-articular (ia) contrast agent administration at 3 Tesla (T), a paired study comparing intravenous (iv) dGEMRIC (standard) with ia-dGEMRIC was performed. Materials and Methods Thirty-five symptomatic patients with suspected cartilage damage underwent ia- and iv-dGEMRIC. MRI was performed with a 3T system wherein the interval between both measurements was 2 weeks. For iv-dGEMRIC, FDA approved Gd-DOTA- was injected intravenously 45 min before the MRI scan. For ia-dGEMRIC, 10-20 mL of a 2 mM solution of Gd- DOTA- was injected under fluoroscopic guidance 30 min before the MRI scan. Results Both ia- and iv-dGEMRIC demonstrated the typical T1Gd pattern in hip joint cartilage with increasing values toward the superior regions in acetabular cartilage reflecting the higher glycosaminoglycan (GAG) content in the main weight-bearing area. Correlation analysis revealed a moderate correlation between both techniques (r = 0.439, P-value < 0.001), whereas the T1 Gd values for iv-dGEMRIC were significantly higher than those for ia-dGEMRIC. This corresponds with the Bland-Altman plot analysis, which revealed a systemic bias (higher T1Gd values after iv gadolinium application) of ∼70 ms. Conclusion Ia-dGEMRIC was able to reveal the characteristic T1Gd pattern in hip joint cartilage confirming the sensitivity of ia-dGEMRIC for GAG. In addition, there was a significant correlation between iv-dGEMRIC and ia-dGEMRIC. However, the T1Gd values after ia contrast media application were significantly lower than those after iv application that has to be considered for future studies. J. Magn. Reson. Imaging 2014;39:94-102. © 2013 Wiley Periodicals, Inc. Copyright © 2013 Wiley Periodicals, Inc.
    view abstract10.1002/jmri.24096
  • Experimental and computational studies on the femoral fracture risk for advanced core decompression
    Tran, T.N. and Warwas, S. and Haversath, M. and Classen, T. and Hohn, H.P. and Jäger, M. and Kowalczyk, W. and Landgraeber, S.
    Clinical Biomechanics 29 (2014)
    Background Two questions are often addressed by orthopedists relating to core decompression procedure: 1) Is the core decompression procedure associated with a considerable lack of structural support of the bone? and 2) Is there an optimal region for the surgical entrance point for which the fracture risk would be lowest? As bioresorbable bone substitutes become more and more common and core decompression has been described in combination with them, the current study takes this into account. Methods Finite element model of a femur treated by core decompression with bone substitute was simulated and analyzed. In-vitro compression testing of femora was used to confirm finite element results. Findings The results showed that for core decompression with standard drilling in combination with artificial bone substitute refilling, daily activities (normal walking and walking downstairs) are not risky for femoral fracture. The femoral fracture risk increased successively when the entrance point is located further distal. The critical value of the deviation of the entrance point to a more distal part is about 20 mm. Interpretation The study findings demonstrate that optimal entrance point should locate on the proximal subtrochanteric region in order to reduce the subtrochanteric fracture risk. Furthermore the consistent results of finite element and in-vitro testing imply that the simulations are sufficient. © 2014 Elsevier Ltd.
    view abstract10.1016/j.clinbiomech.2014.02.001
  • Functional interest of an articulating spacer in two-stage infected total knee arthroplasty revision
    Classen, T. and von Knoch, M. and Wernsmann, M. and Landgraeber, S. and Löer, F. and Jäger, M.
    Orthopaedics and Traumatology: Surgery and Research 100 (2014)
    Introduction: Deep periprosthetic infection is one of the most serious complications after total knee replacement. The two-stage procedure with implantation of a temporary cement spacer and later re-implantation of a revision total knee prosthesis is an accepted procedural standard. The use of articulating spacers has been proposed to enhance ease of revision and functional results. Patients and methods: Twenty-three patients treated with an articulating spacer were retrospectively studied. All patients had undergone a two-stage surgery. The infected prosthesis was explanted and the femoral component was sterilized and re-implanted. On the tibial side a block of gentamicin-loaded bone cement was produced intraoperatively using specially manufactured templates. Eighteen total knee arthroplasty revisions and 5 arthrodesis were finally performed. Results: A total of three (13%) re-infections occurred 5-20 months after revision total knee arthroplasty in a mean follow-up period of 47 months. Prior to re-implantation, flexion with the articulating spacer ranged between 15 and 100° (mean 68 ± 28°). The average postoperative flexion after re-implantation of total knee replacement was 105 ± 11°. Conclusion: The articulating spacer used in this study appears to be as effective as the standard procedures in terms of re-infection risk rate and postoperative range of motion recovery. Level of evidence: Level IV. © 2014 Elsevier Masson SAS.
    view abstract10.1016/j.otsr.2014.01.010
  • Functional interest of an articulating spacer in two-stage infected total knee arthroplasty revision
    Classen, T. and von Knoch, M. and Wernsmann, M. and Landgraeber, S. and Löer, F. and Jäger, M.
    Revue de Chirurgie Orthopedique et Traumatologique 100 (2014)
    Deep periprosthetic infection is one of the most serious complications after total knee replacement. The two-stage procedure with implantation of a temporary cement spacer and later re-implantation of revision total knee prosthesis is an accepted procedural standard. The use of articulating spacers has been proposed to enhance ease of revision and functional results. Patients and methods: Twenty-three patients treated with an articulating spacer were retrospectively studied. All patients had undergone a two-stage surgery. The infected prosthesis was explanted and the femoral component was sterilized and re-implanted. On the tibial side, a block of gentamicin-loaded bone cement was produced intraoperatively using specially manufactured templates. Eighteen total knee arthroplasty revisions and 5 arthrodesis were finally performed. Results: A total of three (13%) re-infections occurred 5-20 months after revision of total knee arthroplasty in a mean follow-up period of 47 months. Prior to re-implantation, flexion with the articulating spacer ranged between 15° and 100° (mean 68°. ±. 28°). The average postoperative flexion after re-implantation of TKR was 105°. ±. 11°. Conclusion: The articulating spacer used in this study appears to be as effective as the standard procedures in terms of re-infection risk rate and postoperative range of motion recovery. Level of evidence: Level IV. © 2014 Elsevier Masson SAS.
    view abstract10.1016/j.rcot.2014.03.031
  • Inflammation-induced hyperalgesia: Effects of timing, dosage, and negative affect on somatic pain sensitivity in human experimental endotoxemia
    Wegner, A. and Elsenbruch, S. and Maluck, J. and Grigoleit, J.-S. and Engler, H. and Jäger, M. and Spreitzer, I. and Schedlowski, M. and Benson, S.
    Brain, Behavior, and Immunity 41 (2014)
    Background: Inflammation-induced pain amplification and hypersensitivity play a role in the pathophysiology of numerous clinical conditions. Experimental endotoxemia has recently been implemented as model to analyze immune-mediated processes in human pain. In this study, we aimed to analyze dose- and time-dependent effects of lipopolysaccharide (LPS) on clinically-relevant pain models for musculoskeletal and neuropathic pain as well as the interaction among LPS-induced changes in inflammatory markers, pain sensitivity and negative affect. Methods: In this randomized, double-blind, placebo-controlled study, healthy male subjects received an intravenous injection of either a moderate dose of LPS (0.8. ng/kg Escherichia coli), low-dose LPS (0.4. ng/kg), or saline (placebo control group). Pressure pain thresholds (PPT), mechanical pain sensitivity (MPS), and cold pain sensitivity (CP) were assessed before and 1, 3, and 6. h post injection to assess time-dependent LPS effects on pain sensitivity. Plasma cytokines (TNF-α, IL-6, IL-8, IL-10) and state anxiety were repeatedly measured before, and 1, 2, 3, 4, and 6. h after injection of LPS or placebo. Results: LPS administration induced a systemic immune activation, reflected by significant increases in cytokine levels, body temperature, and negative mood with pronounced effects to the higher LPS dose. Significant decreases of PPTs were observed only 3. h after injection of the moderate dose of LPS (0.8. ng/kg). MPS and CP were not affected by LPS-induced immune activation. Correlation analyses revealed that decreased PPTs were associated with peak IL-6 increases and negative mood. Conclusions: Our results revealed widespread increases in musculoskeletal pain sensitivity in response to a moderate dose of LPS (0.8. ng/kg), which correlate both with changes in IL-6 and negative mood. These data extend and refine existing knowledge about immune mechanisms mediating hyperalgesia with implications for the pathophysiology of chronic pain and neuropsychiatric conditions. © 2014 Elsevier Inc.
    view abstract10.1016/j.bbi.2014.05.001
  • Interaction with mesenchymal stem cells provokes natural killer cells for enhanced IL-12/IL-18-induced interferon-gamma secretion
    Thomas, H. and Jäger, M. and Mauel, K. and Brandau, S. and Lask, S. and Flohé, S.B.
    Mediators of Inflammation 2014 (2014)
    Tissue injury induces an inflammatory response accompanied by the recruitment of immune cells and of mesenchymal stem cells (MSC) that contribute to tissue regeneration. After stimulation with interleukin- (IL-) 12 and IL-18 natural killer (NK) cells secrete the proinflammatory cytokine interferon- (IFN-) γ. IFN-γ plays a crucial role in the defense against infections and modulates tissue regeneration. In consideration of close proximity of NK cells and MSC at the site of injury we investigated if MSC could influence the ability of NK-cells to produce IFN-γ. Coculture experiments were performed with bone marrow-derived human MSC and human NK cells. MSC enhanced the ability of IL-12/IL-18-stimulated NK cells to secrete IFN-γ in a dose-dependent manner. This activation of NK cells was dependent on cell-cell contact as well as on soluble factors. The increased IFN-γ secretion from NK cells after contact with MSC correlated with an increased level of intracellular IFN-γ. Alterations in the IL-12 signaling pathway including an increased expression of the IL-12 β 1 receptor subunit and an increased phosphorylation of signal transducer and activator of transcription 4 (STAT4) could be observed. In conclusion, MSC enhance the IFN-γ release from NK cells which might improve the defense against infections at the site of injury but additionally might affect tissue regeneration. © 2014 Heike Thomas et al.
    view abstract10.1155/2014/143463
  • Mesenchymal stem cells augment the anti-bacterial activity of neutrophil granulocytes
    Brandau, S. and Jakob, M. and Bruderek, K. and Bootz, F. and Giebel, B. and Radtke, S. and Mauel, K. and Jäger, M. and Flohé, S.B. and Lang, S.
    PLoS ONE 9 (2014)
    Methodology/Principal Findings: We isolated MSCs from human bone-marrow (bmMSCs) and human salivary gland (pgMSCs). Expression levels of TLR4 and LPS-responsive molecules were determined by flow cytometry and quantitative PCR. Cytokine release was determined by ELISA. The effect of supernatants from unstimulated and LPS-stimulated MSCs on recruitment, cytokine secretion, bacterial clearance and oxidative burst of polymorphonuclear neutrophil granulocytes (PMN) was tested in vitro. Despite minor quantitative differences, bmMSCs and pgMSCs showed a similar cell biological response to bacterial endotoxin. Both types of MSCs augmented anti-microbial functions of PMNs LPS stimulation, particularly of bmMSCs, further augmented MSC-mediated activation of PMN. Conclusions/Significance: This study suggests that MSCs may contribute to the resolution of infection and inflammation by promoting the anti-microbial activity of PMNs. This property is exerted by MSCs derived from both the bone-marrow and peripheral glandular tissue. Copyright: © 2014 Brandau et al. Background: Mesenchymal stem cells (MSCs) participate in the regulation of inflammation and innate immunity, for example by responding to pathogen-derived signals and by regulating the function of innate immune cells. MSCs from the bone-marrow and peripheral tissues share common basic cell-biological functions. However, it is unknown whether these MSCs exhibit different responses to microbial challenge and whether this response subsequently modulates the regulation of inflammatory cells by MSCs. © 2014 Brandau et al.
    view abstract10.1371/journal.pone.0106903
  • Prostacyclin suppresses twist expression in the presence of indomethacin in bone marrow- derived mesenchymal stromal cells
    Kemper, O. and Herten, M. and Fischer, J. and Haversath, M. and Beck, S. and Classen, T. and Warwas, S. and Tassemeier, T. and Landgraeber, S. and Lensing-Höhn, S. and Krauspe, R. and Jäger, M.
    Medical Science Monitor 20 (2014)
    Background: Iloprost, a stable prostacyclin I2 analogue, seems to have an osteoblast-protective potential, whereas indomethacin suppresses new bone formation. The aim of this study was to investigate human bone marrow stromal cell (BMSC) proliferation and differentiation towards the osteoblastic lineage by administration of indomethacin and/or iloprost. Material/Methods: Human bone marrow cells were obtained from 3 different donors (A=26 yrs/m; B=25 yrs/f, C=35 yrs/m) via vacuum aspiration of the iliac crest followed by density gradient centrifugation and flow cytometry with defined antigens (CD105+/73+/45–/14–). The cells were seeded and incubated as follows: without additives (Group 0; donor A/B/C), with 10–7 M iloprost only (Group 0+ilo; A/B), with indomethacin only in concentrations of 10–6 M (Group 1, A), 10–5 M (Group 2, B), 10–4 M (Group 3, A/B), and together with 10–7 M iloprost (Groups 4–6, A/B/C). On Day 10 and 28, UV/Vis spectrometric and immunocytochemical assays (4 samples per group and donor) were performed to investigate cell proliferation (cell count measurement) and differentiation towards the osteoblastic lineage (CD34–, CD45–, CD105+, type 1 collagen (Col1), osteocalcin (OC), alkaline phosphatase (ALP), Runx2, Twist, specific ALP-activity). Results: Indomethacin alone suppressed BMSC differentiation towards the osteoblastic lineage by downregulation of Runx2, Col1, and ALP. In combination with indomethacin, iloprost increased cell proliferation and differentiation and it completely suppressed Twist expression at Day 10 and 28. Iloprost alone did not promote cell proliferation, but moderately enhanced Runx2 and Twist expression. However, the proliferative effects and the specific ALP-activity varied donor-dependently. Conclusions: Iloprost partially antagonized the suppressing effects of indomethacin on BMSC differentiation towards the osteoblast lineage. It enhanced the expression of Runx2 and, only in the presence of indomethacin, it completely suppressed Twist. Thus, in the treatment of avascular osteonecrosis or painful bone marrow edema, the undesirable effects of indomethacin might be counterbalanced by iloprost. © Med Sci Monit, 2014.
    view abstract10.12659/MSM.890953
  • The pathology of orthopedic implant failure is mediated by innate immune system cytokines
    Landgraeber, S. and Jäger, M. and Jacobs, J.J. and Hallab, N.J.
    Mediators of Inflammation 2014 (2014)
    All of the over 1 million total joint replacements implanted in the US each year are expected to eventually fail after 15-25 years of use, due to slow progressive subtle inflammation at the bone implant interface. This inflammatory disease state is caused by implant debris acting, primarily, on innate immune cells, that is, macrophages. This slow progressive pathological bone loss or "aseptic loosening" is a potentially life-threatening condition due to the serious complications in older people (>75 yrs) of total joint replacement revision surgery. In some people implant debris (particles and ions from metals) can influence the adaptive immune system as well, giving rise to the concept of metal sensitivity. However, a consensus of studies agrees that the dominant form of this response is due to innate reactivity by macrophages to implant debris where both danger (DAMP) and pathogen (PAMP) signalling elicit cytokine-based inflammatory responses. This paper discusses implant debris induced release of the cytokines and chemokines due to activation of the innate (and the adaptive) immune system and the subsequent formation of osteolysis. Different mechanisms of implant-debris reactivity related to the innate immune system are detailed, for example, danger signalling (e.g., IL-1 β, IL-18, IL-33, etc.), toll-like receptor activation (e.g., IL-6, TNF- α, etc.), apoptosis (e.g., caspases 3-9), bone catabolism (e.g., TRAP5b), and hypoxia responses (Hif1- α). Cytokine-based clinical and basic science studies are in progress to provide diagnosis and therapeutic intervention strategies. © 2014 Stefan Landgraeber et al.
    view abstract10.1155/2014/185150
  • A prospective randomized peri- and post-operative comparison of the minimally invasive anterolateral approach versus the lateral approach.
    Landgraeber, S. and Quitmann, H. and Guth, S. and Haversath, M. and Kowalczyk, W. and Kecskemethy, A. and Heep, H. and Jäger, M.
    Orthopedic reviews 5 (2013)
    There is still controversy as to whether minimally invasive total hip arthroplasty enhances the postoperative outcome. The aim of this study was to compare the outcome of patients who underwent total hip replacement through an anterolateral minimally invasive (MIS) or a conventional lateral approach (CON). We performed a randomized, prospective study of 75 patients with primary hip arthritis, who underwent hip replacement through the MIS (n=36) or CON (n=39) approach. The Western Ontario and McMaster Universities Osteoarthritis Index and Harris Hip score (HHS) were evaluated at frequent intervals during the early postoperative follow-up period and then after 3.5 years. Pain sensations were recorded. Serological and radiological analyses were performed. In the MIS group the patients had smaller skin incisions and there was a significantly lower rate of patients with a positive Trendelenburg sign after six weeks postoperatively. After six weeks the HHS was 6.85 points higher in the MIS group (P=0.045). But calculating the mean difference between the baseline and the six weeks HHS we evaluated no significant differences. Blood loss was greater and the duration of surgery was longer in the MIS group. The other parameters, especially after the twelfth week, did not differ significantly. Radiographs showed the inclination of the acetabular component to be significantly higher in the MIS group, but on average it was within the same permitted tolerance range as in the CON group. Both approaches are adequate for hip replacement. Given the data, there appears to be no significant long term advantage to the MIS approach, as described in this study.
    view abstract10.4081/or.2013.e19
  • Advanced core decompression, a new treatment option of avascular necrosis of the femoral head-a first follow-up
    Landgraeber, S. and Theysohn, J.M. and Classen, T. and Jäger, M. and Warwas, S. and Hohn, H.-P. and Kowalczyk, W.
    Journal of Tissue Engineering and Regenerative Medicine 7 (2013)
    Aseptic necrosis of the femoral head (AVN) leads to destruction of the affected hip joint, predominantly in younger patients. Advanced core decompression (ACD) is a new technique that may allow better removal of the necrotic tissue by using a new percutaneous expandable reamer. A further modification is the refilling of the drill hole and the defect with an injectable, hard-setting, composite calcium sulphate (CaSO4)-calcium phosphate (CaPO4) bone graft substitute. Compression tests were performed on seven pairs of femoral cadaver bones. One femur of each pair was treated with ACD, while the opposite side remained untreated. Clinically, the postoperative outcome of 27 hips in 23 patients was performed by physical examination 6weeks after ACD and at average follow-up of 9.69months, and compared with the preoperative results. MRI was used to assess the removal of the necrotic tissue, any possible progression of AVN and evaluation of collapse. In the biomechanical analysis, the applied maximum compression force that caused the fracture did not significantly differ from the untreated opposite side. The overall results of postoperative physical examinations were significantly better than preoperatively. Five hips (18.5%) were converted to a total hip replacement. The follow-up MRIs of the other patients showed no progression of the necrotic area. The first follow-up results of ACD have been encouraging for the early stages of aseptic necrosis of the femoral head. In our opinion, an assured advantage is the high stability of the femoral neck after ACD, which allows quick rehabilitation. © 2012 John Wiley & Sons, Ltd.
    view abstract10.1002/term.1481
  • Assessment and management of chronic pain in patients with stable total hip arthroplasty
    Classen, T. and Zaps, D. and Landgraeber, S. and Li, X. and Jäger, M.
    International Orthopaedics 37 (2013)
    Total hip arthroplasty (THA) is one of the most successful operations that can restore function and relieve pain. Although a majority of the patients achieve significant pain relief after THA, there are a number of patients that develop chronic pain for unknown reasons. A literature search was performed looking for chronic pain after total hip arthroplasty and stable THA. Major causes of chronic pain include aseptic loosening or infection. However, there is a subset of patients with a stable THA that present with chronic pain which can have several aetiologies. These include soft tissue, bony, neurological, vascular and psychological causes. Essential for successful treatment is the ability to make the correct diagnosis. Thus therapy may be either non-operative or operative. In addition, diagnosis and management often may require multidisciplinary approaches to successfully alleviate chronic pain in these patients with a stable prosthesis. © 2012 Springer-Verlag Berlin Heidelberg.
    view abstract10.1007/s00264-012-1711-6
  • Bone marrow concentrate for autologous transplantation in minipigs: Characterization and osteogenic potential of mesenchymal stem cells
    Herten, M. and Grassmann, J.P. and Sager, M. and Benga, L. and Fischer, J.C. and Jäger, M. and Betsch, M. and Wild, M. and Hakimi, M. and Jungbluth, P.
    Veterinary and Comparative Orthopaedics and Traumatology 26 (2013)
    Autologous bone marrow plays an increasing role in the treatment of bone, cartilage and tendon healing disorders. Cell-based therapies display promising results in the support of local regeneration, especially therapies using intra-operative one-step treatments with autologous progenitor cells. In the present study, bone marrow-derived cells were concentrated in a point-of-care device and investigated for their mesenchymal stem cell (MSC) characteristics and their osteogenic potential. Bone marrow was harvested from the iliac crest of 16 minipigs. The mononucleated cells (MNC) were concentrated by gradient density centrifugation, cultivated, characterized by flow cytometry and stimulated into osteoblasts, adipocytes, and chondrocytes. Cell differentiation was investigated by histological and immunohistological staining of relevant lineage markers. The proliferation capacity was determined via colony forming units of fibroblast and of osteogenic alkalinephosphatase-positive-cells. The MNC could be enriched 3.5-fold in nucleated cell concentrate in comparison to bone marrow. Flow cytometry analysis revealed a positive signal for the MSC markers. Cells could be differentiated into the three lines confirming the MSC character. The cellular osteogenic potential correlated significantly with the percentage of newly formed bone in vivo in a porcine metaphyseal longbone defect model. This study demonstrates that bone marrow concentrate from minipigs display cells with MSC character and their osteogenic differentiation potential can be used for osseous defect repair in autologous transplantations. © Schattauer 2013.
    view abstract10.3415/VCOT-11-11-0165
  • Can thrombin-activated platelet releasate compensate the age-induced decrease in cell proliferation of MSC?
    Vogl, M. and Fischer, J. and Jäger, M. and Zilkens, C. and Krauspe, R. and Herten, M.
    Journal of Orthopaedic Research 31 (2013)
    Mesenchymal progenitor cells (MSCs) are promising for cell-based regeneration therapies. In elderly patients a reduced proliferation of MSCs has been described. Platelet-rich plasma (PRP) contains important factors necessary for osteogenic regeneration. The aim of this study was to find out whether the age-induced decrease in cell proliferation can be compensated by the use of supernatant of centrifuged, activated PRP (tPR). MSCs of donors of three age groups (A: young, 14-16 years, B: middle age, 36-46 years, C: older, 74-83 years) were expanded with 20% FCS alone or supplemented with thrombin-activated platelet releasate (tPR) (1%, 2.5%, and 5%) or platelet-poor plasma (PPP 5%). Cell proliferation and differentiation was measured on days 0, 3, and 7. Proliferation increased significantly in groups A and B with tPR, and non-significantly in group C. The generation times of MSCs of elderly patients were significantly increased in group C compared to groups A and B. Addition of 1% or 2.5% tPR significantly reduced population doubling times of all age groups. Adding tPR stimulates the proliferation rate of MSCs independent of donor age. For juvenile and middle-aged patients this influence was significant. Cells differentiation into osteoblasts was not influenced by addition of tPR. © 2013 Orthopaedic Research Society.
    view abstract10.1002/jor.22433
  • Combined salter-pemberton pelvic osteotomy
    Hövel, M. and Jäger, M.
    Operative Orthopadie und Traumatologie 25 (2013)
    Objective: In simple pelvic osteotomy in childhood the aim is for better lateral roofing, a safe centering of the femoral head and tuning between the volumes of the acetabulum and the femoral head. By the combination of anterior modified Pemberton osteotomy with dorsal osteotomy according to Salter these objectives can be achieved. Indications: Dysplasia of the acetabulum in patients between 2 years old and adolescence, subluxation and dislocation of the femoral head, also in neurological diseases as cerebral palsy and hypercontainment in Legg-Calvé-Perthes disease. Contraindications: Critically small pelvic bones in toddlers younger than 18 months, children with a delay in skeletal formation. In patients aged more than 15 years if the symphysis is too taut for an effectual pivoting of the acetabulum and the acetabulum has no potential for future maturing. Surgical technique: Surgery is carried out by making a skin incision by the iliac crest ending in the middle of the groin, the cartilaginous iliac apophysis is split and the periosteum is elevated from the medial and lateral wall of the ilium to the inner pelvic ring. A K-wire is used to mark the level and the center of the osteotomy and dorsal to the K-wire a straight osteotomy is performed with a Gigli saw and anteriorly an arc-shaped and tilted cut is made with a chisel. The distal iliac fragment is rotated widely outwards and forwards and a triangular bone graft is removed from the anterior part of the iliac crest. The graft is inserted into the opened up osteotomy, three K-wires are used to fix the desired position of the iliac fragments and the two halves of the iliac apophysis are sutured together. Postoperative management: After the operation uncooperative children receive a scotch cast for 4 weeks. Cooperative children are mobilized after 3 weeks of bed rest. Partial weight-bearing is allowed after 6 weeks and full weight-bearing after 8-10 weeks. Results: A total of 56 combined Salter-Pemberton pelvic osteotomies were performed in 49 patients from 1999 to 2008. The results of these studies demonstrate that this osteotomy is a safe and effective procedure which enables not only sufficient correction in classical dysplasia of the hip joint but also in high grade dislocation of the hip joint caused by cerebral palsy. © 2013 Springer-Verlag Berlin Heidelberg.
    view abstract10.1007/s00064-013-0239-2
  • Histological variations of the glenoid labrum in dogs
    Sager, M. and Herten, M. and Dreiner, L. and Engelhardt, E. and Assheuer, J. and Kramer, M. and Jäger, M.
    Journal of Veterinary Medicine Series C: Anatomia Histologia Embryologia 42 (2013)
    As the structure and clinical meaning of the canine glenoid labrum are repeatedly disputed up to now, an anatomical histological description of the structure and its varieties in older dogs is carried out. In this study, 20 shoulder joints are histologically and immunohistologically examined. The glenoid labrum (GL) is composed of up to three different zones: a transition zone composed of fibre cartilage with collagen fibres arranged like a fishnet-like pattern, a zone of circularly leading fibre bundles and a meniscoid fold with synovial coverage. A variable recess exists between the GL and the joint surface. © 2013 Blackwell Verlag GmbH.
    view abstract10.1111/ahe.12035
  • Measurement of the silver ion concentration in wound fluids after implantation of silver-coated megaprostheses: Correlation with the clinical outcome
    Hussmann, B. and Johann, I. and Kauther, M.D. and Landgraeber, S. and Jäger, M. and Lendemans, S.
    BioMed Research International 2013 (2013)
    Background. Tumor patients and patients after traumas are endangered by a reduced immune defense, and a silver coating on their megaprostheses may reduce their risks of infection. The aim of this study was to determine the silver ion concentration directly measured from the periprosthetic tissue and the influence on the clinical outcome. Material and Methods. Silver ions were evaluated in 5 mL wound fluids two days postoperatively and in blood patients 7 and 14 days after surgery using inductively coupled plasma emission spectrometry in 18 patients who underwent total joint replacement with a silver-coated megaendoprosthesis. Results. The concentration of silver ions averaged 0.08 parts per million. Patients who showed an increased silver concentration in the blood postoperatively presented a lower silver concentration in the wound fluids and a delayed decrease in C-reactive protein levels. There were significantly fewer reinfections and shorter hospitalization in comparison with a group that did not receive a silver-coated megaprosthesis. Conclusion. An increased concentration of silver in the immediate surroundings of silver-coated prostheses was demonstrated for the first time in cohorts of patients with trauma or tumors. An elevated concentration of silver ions in the direct periprosthetic tissue may have reduced the infection rate. © 2013 B. Hussmann et al.
    view abstract10.1155/2013/763096
  • Mesenchymal stem cells from osteoporotic patients feature impaired signal transduction but sustained osteoinduction in response to BMP-2 stimulation
    Prall, W.C. and Haasters, F. and Heggebö, J. and Polzer, H. and Schwarz, C. and Gassner, C. and Grote, S. and Anz, D. and Jäger, M. and Mutschler, W. and Schieker, M.
    Biochemical and Biophysical Research Communications 440 (2013)
    Osteoporotic fractures show reduced callus formation and delayed bone healing. Cellular sources of fracture healing are mesenchymal stem cells (MSC) that differentiate into osteoblasts by stimulation with osteoinductive cytokines, such as BMP-2. We hypothesized that impaired signal transduction and reduced osteogenic differentiation capacity in response to BMP-2 may underlie the delayed fracture healing. Therefore, MSC were isolated from femoral heads of healthy and osteoporotic patients. Grouping was carried out by bone mineral densitometry in an age-matched manner. MSC were stimulated with BMP-2. Signal transduction was assessed by western blotting of pSMAD1/5/8 and pERK1/2 as well as by quantitative RT-PCR of Runx-2, Dlx5, and Osteocalcin. Osteogenic differentiation was assessed by quantifying Alizarin Red staining. Osteoporotic MSC featured an accurate phosphorylation pattern of SMAD1/5/8 but a significantly reduced activation of ERK1/2 by BMP-2 stimulation. Furthermore, osteoporotic MSC showed significantly reduced basal expression levels of Runx-2 and Dlx5. However, Runx-2, Dlx5, and Osteocalcin expression showed adequate up-regulation due to BMP-2 stimulation. The global osteogenic differentiation in standard osteogenic differentiation media was reduced in osteoporotic MSC. Nevertheless, osteoporotic MSC were shown to feature an adequate induction of osteogenic differentiation due to BMP-2 stimulation. Taken together, we here demonstrate osteoporosis associated alterations in BMP-2 signaling but sustained specific osteogenic differentiation capacity in response to BMP-2. Therefore, BMP-2 may represent a promising therapeutic agent for the treatment of fractures in osteoporotic patients. © 2013 Elsevier Inc. All rights reserved.
    view abstract10.1016/j.bbrc.2013.09.114
  • Osteoblastic potency of bone marrow cells cultivated on functionalized biometals with cyclic RGD-peptide
    Jäger, M. and Böge, C. and Janissen, R. and Rohrbeck, D. and Hülsen, T. and Lensing-Höhn, S. and Krauspe, R. and Herten, M.
    Journal of Biomedical Materials Research - Part A 101 (2013)
    The fixation of cementless endoprostheses requires excellent fixation at the bone implant interface. Although the surface structures of these implants are designed to promote osteoblastic differentiation, poor bone quality may prevent or delay osseointegration. There is evidence that RGD peptides known as recognition motifs for various integrins, promote cellular adhesion, influence cellular proliferation, and differentiation of local cells. In this study, five different metal surfaces were analyzed: Sandblasted (TiSa) and polished (TiPol) Ti6Al4V, porocoated (CCPor) and polished (CCPol) cobalt chrome and polished stainless steel (SS) were coated by ethanol amine and poly(ethylene glycol) to attach covalently RGD peptides. Human mesenchymal stromal cells of healthy donors were cultivated onto prior functionalized metal surfaces for 14 days without osteogenic stimulation. Cell proliferation and differentiation were quantitatively evaluated for native (I), NaOH pre-activated (II), NaOH pre-activated, and PEG-coated (III) as well as for RGD (IV) coated surfaces. The RGD immobilization efficiency was analyzed by epi-fluorescence spectroscopy, cell morphology was documented by light and scanning electron microscopy. The RGD-binding efficiency was TiSa > TiPol > SS > CCPor > CCPol. RGD coated surfaces showed the highest average cell proliferation on CCPol > SS > CCPor > TiSa ≥ TiPol, whereas cellular differentiation mostly correlated with the observed proliferation results, such as CCPol > TiSa > SS > CCPor > TiPol. Considering statistical analyses (significance level of α = 0.05), the RGD-coating of all biometals in comparison and in respect of their particular controls showed no significant improvement in cellular proliferation and osteoblastic differentiation. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 2905-2914, 2013. Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.
    view abstract10.1002/jbm.a.34590
  • RANKL-associated suppression of particle-induced osteolysis in an aged model of Calcitonin and α-CGRP deficiency
    Kauther, M.D. and Neuerburg, C. and Wefelnberg, F. and Bachmann, H.S. and Schlepper, R. and Hilken, G. and Broecker-Preuss, M. and Grabellus, F. and Schilling, A.F. and Jäger, M. and Wedemeyer, C.
    Biomaterials 34 (2013)
    An aging population with higher bone turnover intensifies the need for joint replacement surgery. However, particle-induced osteolysis (PIO) remains a major cause of early implant loosening. Differences in bone remodeling between young and aged Calcitonin (CT)- and α-CGRP (Calcitonin gene-related peptide)-deficient mice (Calca-/-) might modify our previous findings regarding CT/α-CGRP in PIO. This may have important implications for PIO in an aging population. Four groups of twelve-month-old wild-type and Calca-/- mice underwent either SHAM surgery with and without CT, or polyethylene-particle implantation with related treatment. Morphometric changes were detected using μ-CT, histomorphometric analysis and by counting TRAP+ cells (osteoclast-staining). Bone remodeling was assessed using serum and urinary markers. There was no osteolysis in aged particle-treated Calca-/- animals and the effect of CT on PIO was reduced compared to wild-type mice. However, there were significantly higher numbers of TRAP+ cells in Calca-/- animals, and bone remodeling markers revealed a significant increase in OPG/OCN and a significant reduction in RANKL compared to aged wild-type mice. CT/α-CGRP modulates bone cell activity in PIO in aged mice in a way that is distinct from young animals. This may have implications for the treatment of PIO in the periprosthetic surface of joint replacements in an aging population. © 2013 Elsevier Ltd.
    view abstract10.1016/j.biomaterials.2013.01.034
  • Schwannoma of the femoral nerve: A rare differential diagnosis of leg pain
    Schulte, P. and Sandalcioglu, I.E. and Grabellus, F. and Baba, H. and Sure, U. and Jäger, M.
    Schmerz 27 (2013)
    Background: Schwannomas (neurinomas) are among the most frequent peripheral nerve tumors. Nevertheless, these are seldom located in the lower extremities in association with the femoral nerve. Clinical presentation: In this case, the occurrence of a schwannoma adjacent to the femoral nerve is described in a patient presenting with nonspecific pain in the thigh accompanied by a palpable mass. Sensory and motor deficits were not present. Further examinations by MRI and biopsy followed by histopathology, revealed the diagnosis of a schwannoma. The tumor was completely excised. Conclusion: Although schwannomas of the lower extremities are rare, they should be included in the differential diagnosis. Knowing the typical clinical symptoms, radiological signs, and histopathological findings, diagnosis should be straight forward. © 2013 Springer-Verlag Berlin Heidelberg.
    view abstract10.1007/s00482-013-1311-4
  • Stingray injury - A harmless injury for surfers?
    Kauther, M.D. and Wedemeyer, C. and Lendemans, S. and Hussmann, B. and Waydhas, C. and Jäger, M.
    Sportverletzung-Sportschaden 27 (2013)
    Background: Stingray injuries with potentially lethal outcomes have been described in the medical literature, but a stingray injury to a surfer does not belong to the injuries treated daily in Germany. Patients: We report on a stingray injury to a 31-year-old female with an uncommon course. Results: Diagnostics of and therapy for stingray injuries are described. Conclusion: Stingray stings are painful injuries. In addition to the pain-relieving heat deactivation of the stingray toxin, the wound has to be cleaned to avoid secondary infection. Non-radiopaque foreign bodies should be ruled out by MRI. Stingray bites can cause severe injuries to water sportsmen and women with the need for surgical intervention. © 2013 Georg Thieme Verlag KG Stuttgart - New York.
    view abstract10.1055/s-0033-1335854
  • The distribution of nociceptive innervation in the painful hip: A histological investigation
    Haversath, M. and Hanke, J. and Landgraeber, S. and Herten, M. and Zilkens, C. and Krauspe, R. and Jäger, M.
    Bone and Joint Journal 95 B (2013)
    Our understanding of the origin of hip pain in degenerative disorders of the hip, including primary osteoarthritis, avascular necrosis and femoroacetabular impingement (FAI), is limited. We undertook a histological investigation of the nociceptive innervation of the acetabular labrum, ligamentum teres and capsule of the hip, in order to prove pain- and proprioceptive-associated marker expression. These structures were isolated from 57 patients who had undergone elective hip surgery (44 labral samples, 33 ligamentum teres specimens, 34 capsular samples; in 19 patients all three structures were harvested). A total of 15 000 histological sections were prepared that were investigated immunohistochemically for the presence of protein S-100, 68 kDa neurofilament, neuropeptide Y, nociceptin and substance P. The tissues were evaluated in six representative areas. Within the labrum, pain-associated free nerve ending expression was located predominantly at its base, decreasing in the periphery. In contrast, the distribution within the ligamentum teres showed a high local concentration in the centre. The hip capsule had an almost homogeneous marker expression in all investigated areas. This study showed characteristic distribution profiles of nociceptive and pain-related nerve fibres, which may help in understanding the origin of hip pain. ©2013 The British Editorial Society of Bone & Joint Surgery.
    view abstract10.1302/0301-620X.95B6.30262
  • Validity of gradient-echo three-dimensional delayed gadolinium-enhanced magnetic resonance imaging of hip joint cartilage: A histologically controlled study
    Zilkens, C. and Miese, F. and Herten, M. and Kurzidem, S. and Jäger, M. and König, D. and Antoch, G. and Krauspe, R. and Bittersohl, B.
    European Journal of Radiology 82 (2013)
    Objective: To validate gradient-echo three-dimensional (3D) delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) by means of histological analyses in the assessment of hip joint cartilage. Materials and methods: Twenty-one femoral head specimens collected from 21 patients (7 males, 14 females, mean age: 60.9 ± 9.6 years; range: 37.6-77.3 years), who underwent total hip replacement for symptomatic hip joint osteoarthritis, underwent MRI and histological assessment. A region of 2 cm2 at the weight-bearing area was marked with four pins to enable multi-planar MRI reformatting to be matched with histological sections. MRI was performed at 3 T with a 3D double-echo steady-state (DESS) sequence for morphological cartilage assessment and 3D Volumetric Interpolated Breathhold Examination (VIBE) for T1Gd mapping. Histological sections were evaluated according to the Mankin score system. Total Mankin score, grade of toluidine staining (sensitive for glycosaminoglycan content) and a modified Mankin score classification system with four sub-groups of cartilage damage were correlated with MRI data. Results: Spearman's rho correlation analyses revealed a statistically significant correlation between T1Gd mapping and histological analyses in all categories including total Mankin score (r = -0.658, p-value ≤ 0.001), toluidine staining (r = -0.802, p-value < 0.001) and modified Mankin score (r = -0.716, p-value < 0.001). The correlation between morphological MRI and histological cartilage assessment was statistically significant but inferior to the biochemical cartilage MRI (r-values ranging from -0.411 to 0.525, p-values < 0.001). Conclusions: Gradient-echo dGEMRIC is reliable while offering the unique features of high image resolution and 3D biochemically sensitive MRI for the assessment of early cartilage degeneration. © 2012 Elsevier Ireland Ltd.
    view abstract10.1016/j.ejrad.2012.09.024
  • Cementless second-generation hydroxyapatite CaP-coated tibial component: An 8.7-year follow-up
    Wedemeyer, C. and Kauther, M.D. and Bülbül, M. and Jäger, M. and Peppmüller, R. and Bredendiek, T.
    Archives of Orthopaedic and Trauma Surgery 132 (2012)
    Background This is the first study that reports on the midterm results of 81 patients suffering from arthritis of the knee, treated with a cementless second-generation hydroxyapatite calcium phosphate (CaP)-coated tibial component. Materials and methods Seventy-six knees with osteoarthritis were evaluated according to the Knee Society clinical, functional and radiological score, the Hospital for Special Surgery Rating System and the Patella Score. The clinical and radiological parameters were assessed preoperatively and after a mean follow-up of 8.7 years. Results All the three score systems revealed excellent clinical outcomes after the follow-up period. The mean preoperative Knee Society clinical Score was 124.41 ± 12.99 and the mean postoperative score was 187.07 ± 14.59 at the time of the final consultation (p = 0.0008). The survival rate was 97.5 %. Radiolucency of <1 mm around the uncemented hydroxyapatite CaP-coated tibial component without accompanying pain symptoms was seen in fewer than 6 % of cases. In two cases, a medial cyst, also without other clinical symptoms, was observed beside the tip of the tibial fixation screw. Conclusion These findings indicate that the uncemented second-generation hydroxyapatite CaP-coated tibial component performed well at mid-term follow-up, and provides sufficiently stable bone ingrowth fixation. © Springer-Verlag 2012.
    view abstract10.1007/s00402-012-1608-2
  • Inhibition of osteoclastogenesis by RNA interference targeting RANK
    Ma, R. and Xu, J. and Dong, B. and Kauther, M.D. and Jäger, M. and Wedemeyer, C.
    BMC Musculoskeletal Disorders 13 (2012)
    Background: Osteoclasts and osteoblasts regulate bone resorption and formation to allow bone remodeling and homeostasis. The balance between bone resorption and formation is disturbed by abnormal recruitment of osteoclasts. Osteoclast differentiation is dependent on the receptor activator of nuclear factor NF-kappa B (RANK) ligand (RANKL) as well as the macrophage colony-stimulating factor (M-CSF). The RANKL/RANK system and RANK signaling induce osteoclast formation mediated by various cytokines. The RANK/RANKL pathway has been primarily implicated in metabolic, degenerative and neoplastic bone disorders or osteolysis. The central role of RANK/RANKL interaction in osteoclastogenesis makes RANK an attractive target for potential therapies in treatment of osteolysis. The purpose of this study was to assess the effect of inhibition of RANK expression in mouse bone marrow macrophages on osteoclast differentiation and bone resorption. Methods. Three pairs of short hairpin RNAs (shRNA) targeting RANK were designed and synthesized. The optimal shRNA was selected among three pairs of shRNAs by RANK expression analyzed by Western blot and Real-time PCR. We investigated suppression of osteoclastogenesis of mouse bone marrow macrophages (BMMs) using the optimal shRNA by targeting RANK. Results: Among the three shRANKs examined, shRANK-3 significantly suppressed [88.3%] the RANK expression (p < 0.01). shRANK-3 also brought about a marked inhibition of osteoclast formation and bone resorption as demonstrated by tartrate-resistant acid phosphatase (TRAP) staining and osteoclast resorption assay. The results of our study show that retrovirus-mediated shRANK-3 suppresses osteoclast differentiation and osteolysis of BMMs. Conclusions: These findings suggest that retrovirus-mediated shRNA targeting RANK inhibits osteoclast differentiation and osteolysis. It may appear an attractive target for preventing osteolysis in humans with a potential clinical application. © 2012 Ma et al.; licensee BioMed Central Ltd.
    view abstract10.1186/1471-2474-13-154
  • Multiple myeloma-related deregulation of bone marrow-derived CD34 + hematopoietic stem and progenitor cells
    Bruns, I. and Cadeddu, R.-P. and Brueckmann, I. and Fröbel, J. and Geyh, S. and Büst, S. and Fischer, J.C. and Roels, F. and Wilk, C.M. and Schildberg, F.A. and Hünerlitürkoglu, A.-N. and Zilkens, C. and Jäger, M. and Steidl, U. and Zohren, F. and Fenk, R. and Kobbe, G. and Brors, B. and Czibere, A. and Schroeder, T. and Trumpp, A. and Haas, R.
    Blood 120 (2012)
    Multiple myeloma (MM) is a clonal plasma cell disorder frequently accompanied by hematopoietic impairment. We show that hematopoietic stem and progenitor cells (HSPCs), in particular megakaryocyteerythrocyte progenitors, are diminished in the BM of MM patients. Genomic profiling of HSPC subsets revealed deregulations of signaling cascades, most notably TGF- signaling, and pathways involved in cytoskeletal organization, migration, adhesion, and cell-cycle regulation in the patients. Functionally, proliferation, colony formation, and long-term selfrenewal were impaired as a consequence of activated TGF- signaling. In accordance, TGF- levels in the BM extracellular fluid were elevated and mesenchymal stromal cells (MSCs) had a reduced capacity to support long-term hematopoiesis of HSPCs that completely recovered on blockade of TGF- signaling. Furthermore, we found defective actin assembly and down-regulation of the adhesion receptor CD44 in MM HSPCs functionally reflected by impaired migration and adhesion. Still, transplantation into myelomafree NOG mice revealed even enhanced engraftment and normal differentiation capacities of MM HSPCs, which underlines that functional impairment of HSPCs depends on MM-related microenvironmental cues and is reversible. Taken together, these data implicate that hematopoietic suppression in MM emerges from the HSPCs as a result of MM-related microenvironmental alterations. © 2012 by The American Society of Hematology.
    view abstract10.1182/blood-2011-04-347484
  • PGE2 and BMP-2 in bone and cartilage metabolism: 2 intertwining pathways
    Haversath, M. and Catelas, I. and Li, X. and Tassemeier, T. and Jäger, M.
    Canadian Journal of Physiology and Pharmacology 90 (2012)
    Osteoarthritis and lesions to cartilage tissue are diseases that frequently result in impaired joint function and patient disability. The treatment of osteoarthritis, along with local bone defects and systemic skeletal diseases, remains a significant clinical challenge for orthopaedic surgeons. Several bone morphogenetic proteins (BMPs) are known to have osteoinductive effects, whereof BMP-2 and BMP-7 are already approved for clinical applications. There is growing evidence that the metabolism of bone as well as the cartilage damage associated with the above disease processes are strongly inter-related with the interactions of the inflammation-related pathways (in particular prostaglandin E2 (PGE2)) and osteogenesis (in particular bone morphogenetic protein-2 (BMP-2)). There is strong evidence that the pathways of prostaglandins and bone morphogenetic proteins are intertwined, and they have recently come into focus in several experimental and clinical studies. This paper focuses on PGE2 and BMP-2 intertwining pathways in bone and cartilage metabolism, and summarizes the recent experimental and clinical data.
    view abstract10.1139/y2012-123
  • Assessment of early cartilage degeneration after slipped capital femoral epiphysis using T2 and T2 * mapping
    Miese, F.R. and Zilkens, C. and Holstein, A. and Bittersohl, B. and Kröpil, P. and Mamisch, T.C. and Lanzman, R.S. and Bilk, P. and Blondin, D. and Jäger, M. and Krauspe, R. and Fürst, G.
    Acta Radiologica 52 (2011)
    Background: T2 and T2 * mapping are novel tools to assess cartilage quality. Purpose: To evaluate hip cartilage quality in the long-term follow-up of patients with slipped capital femoral epiphysis (SCFE) with T2 and T2 * mapping. Material and Methods: Thirty-three patients (19 men, 14 women, mean age 24 ±6.0 years, range 18-51 years) with a history of SCFE in 41 hips and 10 healthy controls (seven men, mean age 22 ±4 years) were included. Follow-up period was 12 + 6 (range 4-39 years) years. Coronal T2 and T2 * mapping were performed on a 1.5 T scanner. T2 and T2 * values of the hip articular cartilage were determined in the medial, central, and lateral portion of the hip within the weight bearing zone. Clinical symptoms including pain were assessed with the Harris hip score. Statistical analysis was performed using Mann-Whitney U test and Spearman rank sum test. Results: In hips after SCFE T2 (central portion: 25.71 ms ±4.84 ms vs. 29.71 ms ±7.04 ms, p < 0.05) and T2 * (central portion: 20.76 ms ±3.17 ms vs. 23.06 ms ±2.68 ms, P< 0.01) of cartilage were significantly lower, compared to controls. The differences were most apparent in the lateral portion of the hip articular cartilage. Abnormal cartilage T2 and T2 * were not associated with hip pain or impaired hip function. SCFE was unilateral in 23 cases (70%). In the patients' unaffected hips without SCFE, areas of significantly reduced T2 (central portion: 26.07 ms ±4.27 ms, P < 0.05) and T2 * (lateral portion: 23.23 ms ±2.45 vs. 25.11 ms ±3.01 ms, P < 0.05) were noted. Conclusion: T2 and T2 * mapping of the hip in patients after SCFE are significantly different from healthy controls and may offer additional information about cartilage quality.
    view abstract10.3109/02841851.2010.516015
  • Avascular necrosis of the hip - Diagnosis and treatment
    Drescher, W. and Pufe, T. and Smeets, R. and Eisenhart-Rothe, R.V. and Jäger, M. and Tingart, M.
    Zeitschrift fur Orthopadie und Unfallchirurgie 149 (2011)
    Femoral head necrosis is an ischaemic bone necrosis of traumatic or nontraumatic pathogenesis which can lead to hip joint destruction in young age. It is today the indication for 10 % of all the total hip joint replacements. Known aetiologies of nontraumatic femoral head necrosis are alcoholism, steroids, sickle cell anaemia, caisson, and Gaucher's disease. Further risk factors are chemotherapy, chronic inflammatory bowel disease, systemic lupus erythematosus, and multiple sclerosis, in which also steroids are involved. Gravidity is another risk factor, but still idiopathic pathogenesis is found. In diagnosis, the ARCO-classification of the Association for the Research of Osseous Circulation is essential. While stage 0 can only be found histologically, the reversible early stage 1 shows MR signal changes. In the irreversible early stage 2, first native x-ray changes are seen as lower radiolucency reflects new bone apposition on dead trabeculae. In stage 3, subchondral fracture follows, and in stage 4 secondary arthritis of the hip. Established therapy in stage 1 is core decompression, physiotherapy, and more and more also bisphosphonates. Sufficient data to support extracorporeal shock wave therapy are still lacking. Stem cell therapy seems to be a promising new therapy method in stage 2. In stage 2 and 3 mainly proximal femoral osteotomies and (non)vascularised bone transplantation are performed. In stage 4, depending on size and location of the necrotic zone and pathology of the adjacent bone, resurfacing or short stem hip arthroplasty can be performed. However, conventional THA is still golden standard. The problem and challenge, however, is the often young patient age in femoral head necrosis. Especially chemotherapy-associated osteonecrosis in leukaemia is found in patients in their second decade of life. Therefore, the hip should be preserved as long as possible. © Georg Thieme Verlag KG Stuttgart - New York.
    view abstract10.1055/s-0030-1270984
  • Bridging the gap: Bone marrow aspiration concentrate reduces autologous bone grafting in osseous defects
    Jäger, M. and Herten, M. and Fochtmann, U. and Fischer, J. and Hernigou, P. and Zilkens, C. and Hendrich, C. and Krauspe, R.
    Journal of Orthopaedic Research 29 (2011)
    Although autologous bone grafting represents an effective tool to induce osteogenic regeneration in local bone defects or pseudarthroses, it is associated with significant donor site morbidity and limited by the amount available for grafting. We investigate the potency of bone marrow aspiration concentrate (BMAC) to augment bone grafting and support bone healing. The functional and radiographic outcome of 39 patients with volumetric bone deficiencies treated with BMAC are presented and evaluated in a prospective clinical trial. A collagen sponge (Col) served as scaffold in 12 patients and a bovine hydroxyapatite (HA) was applied in the other 27 individuals. The minimal follow-up was 6 months. Clinical and radiographic findings were completed by in vitro data. All patients showed new bone formation in radiographs during follow-up. However, two patients underwent revision surgery due to a lack in bone healing. In contrast to the Col group, the postoperative bone formation appeared earlier in the HA group (HA group: 6.8 weeks vs. Col group 13.6 weeks). Complete bone healing was achieved in the HA group after 17.3 weeks compared to 22.4 weeks in the Col group. The average concentration factor of BMAC was 5.2 (SD 1.3). Flow cytometry confirmed the mesenchymal nature of the cells. Cells from BMAC created earlier and larger colonies of forming units fibroblasts (CFU-F) compared to cells from bone marrow aspirate. BMAC combined with HA can reduce the time needed for healing of bone defects when compared to BMAC in combination with collagen sponge. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
    view abstract10.1002/jor.21230
  • Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), after slipped capital femoral epiphysis
    Zilkens, C. and Miese, F. and Bittersohl, B. and Jäger, M. and Schultz, J. and Holstein, A. and Kim, Y.-J. and Millis, M.B. and Mamisch, T.C. and Krauspe, R.
    European Journal of Radiology 79 (2011)
    Objective: The aim of this study was to assess the glycosaminoglycan (GAG) content in hip joint cartilage in mature hips with a history of slipped capital femoral epiphysis (SCFE) using delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). Methods: 28 young-adult subjects (32 hips) with a mean age of 23.8 ± 4.0 years (range: 18.1-30.5 years) who were treated for mild or moderate SCFE in adolescence were included into the study. Hip function and clinical symptoms were evaluated with the Harris hip score (HHS) system at the time of MRI. Plain radiographic evaluation included Tonnis grading, measurement of the minimal joint space width (JSW) and alpha-angle measurement. The alpha-angle values were used to classify three sub-groups: group 1 = subjects with normal femoral head-neck offset (alpha-angle < 50°), group 2 = subjects with mild offset decrease (alpha-angle 50°-60°), and group 3 = subjects with severe offset decrease (alpha-angle &gt;60°). Results: There was statistically significant difference noted for the T1 Gd values, lateral and central, between group 1 and group 3 (p-values = 0.038 and 0.041). The T1 Gd values measured within the lateral portion were slightly lower compared with the T1 Gd values measured within the central portion that was at a statistically significance level (p-value < 0.001). HHS, Tonnis grades and JSW revealed no statistically significant difference. Conclusion: By using dGEMRIC in the mid-term follow-up of SCFE we were able to reveal degenerative changes even in the absence of joint space narrowing that seem to be related to the degree of offset pathology. The dGEMRIC technique may be a potential diagnostic modality in the follow-up evaluation of SCFE. © 2010 Elsevier Ireland Ltd. All rights reserved.
    view abstract10.1016/j.ejrad.2010.04.022
  • Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and morphologic MRI of cartilage in the long-term follow-up after Legg-Calvé-Perthes disease (LCPD)
    Holstein, A. and Zilkens, C. and Bittersohl, B. and Jäger, M. and Haamberg, T. and Mamisch, T.C. and Lanzman, R.S. and Kröpil, P. and Blondin, D. and Krauspe, R. and Antoch, G. and Fürst, G. and Miese, F.
    Journal of Medical Imaging and Radiation Oncology 55 (2011)
    Introduction: The purpose of the present study was to evaluate the feasibility of delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) in the detection of cartilage changes versus morphologic imaging in the long-term course of Legg-Calvé-Perthes disease (LCPD). Methods: A total of 31 hips in 26 patients (mean age, 30.0 years; range, 18-54 years) who were diagnosed with LCPD in childhood were included. Twenty-one radiographically normal contralateral hips served as controls. dGEMRIC indices of femoral and acetabular cartilage in the weight-bearing zone. Cartilage morphology was classified on radial PD-weighted images according to the modified Outerbridge classification. Results: Mean dGEMRIC values of cartilage were significantly lower in hips after LCPD than in the radiographically normal contralateral hips (513 ± 100 ms vs. 579 ± 103 ms; P = 0.026). In 24 out of 31 LCPD hips and in 4 out of 21 radiographically normal contralateral hips, morphological cartilage changes were noted. Analysis of variance analysis revealed a significant influence of Outerbridge grading on decreased T1-values (P = 0.031). Conclusion: Our results suggest that dGEMRIC at 1.5 T is suitable to assess cartilage quality changes in the long-term follow-up after LCPD. The evaluation of biochemical cartilage quality with dGEMRIC may provide additional information about early cartilage changes occurring without visible alterations of cartilage morphology. © 2011 The Royal Australian and New Zealand College of Radiologists.
    view abstract10.1111/j.1754-9485.2011.02262.x
  • Efficiency of iloprost treatment for osseous malperfusion
    Jäger, M. and Zilkens, C. and Bittersohl, B. and Matheney, T. and Kozina, G. and Blondin, D. and Krauspe, R.
    International Orthopaedics 35 (2011)
    Insufficient osseous blood supply results in bone marrow oedema (BMO) and/or avascular necrosis (AVN). One treatment option to support osseous perfusion is the application of stable prostacycline analog iloprost. In this clinical study, 95 patients were treated with iloprost for BMO/AVN. One hundred eighty-six bones were affected by BMO/AVN before treatment. Average follow-up was 33.0±17.6 months. Pain levels could be reduced (e.g. visual analogue scale, 5.0±2.2 points reduced to 1.7±2.2 points) and functional scores improved (Harris hip score, 52±21 points to 79±17 points) in the course of treatment. According to current data, healing of advanced stages of osteonecrosis is not possible. However, the results of this case series confirm previous findings that in early stages of insufficient osseous blood flow iloprost can contribute to the relief of pain and improve joint function. © 2010 Springer-Verlag.
    view abstract10.1007/s00264-010-0998-4
  • Physiology and pathophysiology of nitrosative and oxidative stress in osteoarthritic joint destruction
    Ziskoven, C. and Jäger, M. and Kircher, J. and Patzer, T. and Bloch, W. and Brixius, K. and Krauspe, R.
    Canadian Journal of Physiology and Pharmacology 89 (2011)
    Osteoarthritis (OA) is one of the most common chronic diseases, with increasing importance due to increased life expectancy. On a cellular level, the pathophysiology of joint function impairment and ultimate destruction associated with OA remains poorly understood. Free radicals are highly reactive molecules involved in both normal intracellular signal transduction and degenerative cellular processes. An imbalance between the free radical burden and cellular scavenging mechanisms, defined as oxidative stress, has been identified as a relevant factor in OA pathogenesis. This literature review elucidates the involvement of nitrosative and oxidative stress in cellular ageing in joints, cell senescence, and apoptosis. Free radical exposure is known to promote cellular senescence and apoptosis, and the involvement of radical oxygen species (ROS) in inflammation, fibrosis control, and pain nociception has been proven. A relatively novel approach to OA pathophysiology considers the joint to be a dynamic system consisting of 3, continuously interacting compartments, cartilage, synoviaZl tissue, and subchondral bone. Current knowledge concerning free radical involvement in paracrine signalling in OA is reviewed. The interrelationship between oxidative imbalances and OA pathophysiology may provide a novel approach to the comprehension, and therefore modification, of OA disease progression and symptom control.
    view abstract10.1139/Y11-055
  • Regeneration of osteochondral defects in the knee
    Jäger, M. and Bittersohl, B. and Zilkens, C. and Herten, M. and Krauspe, R.
    Zeitschrift fur Orthopadie und Unfallchirurgie 149 (2011)
    The application of autologous cells is a standard procedure for the treatment of chondral lesions of the knee. Here, the most frequently used cells are differentiated chondrocytes (autologous chondrocyte implantation, ACI; matrix-induced autologous chondrocyte implantation, MACI). The enzymatic digestion of cartilage tissue by collagenase and isolation of chondrocytes followed by in vitro cultivation are associated with cellular de- and transdifferentiation. To prevent these effects some authors recommend 3Dcultures and culture medium supplementation of defined growth factors and cytokines. Another aim is the reduction of donor site morbidity. Therefore, different progenitor cell types were tested towards their potential for osteochondral regeneration. In particular, MSC derived from bone marrow include several advantages for the treatment of osteochondral defects such as unproblematic sampling, cultivation techniques, and a relatively high degree of biological safety. This review summarises the basic cellular principles as well as clinical results of cell therapeutics for the regeneration of osteochondral defects in the knee. © Georg Thieme Verlag KG Stuttgart - New York.
    view abstract10.1055/s-0030-1250059
  • Significance of clinical and radiographic findings in young adults after slipped capital femoral epiphysis
    Zilkens, C. and Bittersohl, B. and Jäger, M. and Miese, F. and Schultz, J. and Kircher, J. and Westhoff, B. and Krauspe, R.
    International Orthopaedics 35 (2011)
    The purpose of this study was to assess the clinical and radiographic presentation of young adults in the mid-term follow-up after pinning in situ for mild to moderate slipped capital femoral epiphysis (SCFE). We postulated that there was a correlation between the degree of head-neck-offset decrease and clinical and radiographic signs of hip joint degeneration. Thirty-eight young adults (average age 23.4±3.6 years old) with various grades of femoral head-neck-offset pathologies were assessed clinically via Harris hip score (HHS), Tegner-Lysholm score (TLS) and Short Form 36 (SF-36), and radiographic signs of OAwere measured on plain X-ray films after a follow-up of 11.1±3.8 years. We conclude that clinical and radiographic signs of joint degeneration appear early in the follow-up after SCFE, but there is no linear correlation between offset-pathology and joint degeneration. © 2010 Springer-Verlag.
    view abstract10.1007/s00264-010-1106-5
  • The intertwining pathways in biology and biomechanics in fermoro-acetabular impingement (FAI) patients
    Jäger, M. and Bittersohl, B. and Rosenthal, D. and Hefter, H. and Westhoff, B. and Krauspe, R. and Zilkens, C.
    Procedia IUTAM 2 (2011)
    The biomechanical principles and the biological consequences in femoroacetabular impingement (FAI) are poorly understood in detail. We report our experience in diagnosis, surgical treatment and outcome of more than 50 FAI patients. An algorithm for the diagnosis and treatment of FAI is developed. Recent data confirm the impact of molecular MRI to detect early cartilage damage and the efficiency of gait analysis for monitoring. Surgical elimination of the causative biomechanical deformity is crucial for midterm clinical success, which is strongly presented after 6 months already. Open surgical dislocation of the hip provides an excellent overview allowing different treatment modalities. © 2011 Published by Elsevier Ltd.
    view abstract10.1016/j.piutam.2011.04.008
  • Cell therapy in bone-healing disorders
    Jäger, M. and Hernigou, P. and Zilkens, C. and Herten, M. and Fischer, J. and Krauspe, R.
    Orthopade 39 (2010)
    In addition to stabilizing osteosynthesis and autologous bone transplantation, so-called orthobiologics are playing an increasing role in the treatment of bone-healing disorders. Besides the application of different growth factors, new data in the literature suggest that cell therapeutic agents promote local bone regeneration. Due to ethical and biological considerations, clinical application of progenitor cells for the musculoskeletal system is limited to autologous postpartum stem cells. Here in particular, cell therapy with autologous progenitor cells in one surgical session has delivered first promising results. Based on a review of the literature and on our own experience with 75 patients, this article reviews the rationale and characteristics of the clinical application of cell therapy for the treatment of bony substance defects. Most clinical trials report successful bone regeneration after the application of mixed cell populations from bone marrow. © 2010 Springer Medizin Verlag.
    view abstract10.1007/s00132-009-1583-7
  • Delayed gadolinium-enhanced magnetic resonance imaging of cartilage in the long-term follow-up after perthes disease
    Zilkens, C. and Holstein, A. and Bittersohl, B. and Jäger, M. and Haamberg, T. and Miese, F. and Kim, Y.-J. and Mamisch, T.C. and Krauspe, R.
    Journal of Pediatric Orthopaedics 30 (2010)
    Background: Aim of this study was to assess the glycosaminoglycan content in hip joint cartilage in mature hips with a history of Legg-Calvé- Perthes (LCPD) disease using delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC). Methods: Thirty one hips in 27 adults (mean age: 30.5±10.9y) with LCPD in childhood were included. Mean follow-up after diagnosis was 24.5±11.4 years. Clinical symptoms and standard radiographic parameters were evaluated. dGEMRIC indices were calculated as T1Gd mean values in four coronal MRI slices medially, centrally, and laterally. For comparison, the morphologically normal appearing contra-lateral hips (21 hips) were assessed. Results: The following T1Gd values for the LCPD group were noted: medial (507±100ms), central (543±104ms), and lateral (553±105ms). The total T1Gd mean value was 534±104ms. The difference between LCPD and normal hips was statistically significant only for the medial compartment (P=0.018). Conclusions: Hip joint cartilage after LCPD shows a significant glycosaminoglycan loss in the medial compartment while this decrease is less apparent centrally and laterally. dGEMRIC allows direct assessment of cartilage matrix biochemistry and may depict the complex damage pattern of hip joint cartilage after LCPD spatially and qualitatively better than other radiographic methods. Level of Evidence: Prognostic study, Level II-1 (retrospective study). Copyright © 2010 by Lippincott Williams & Wilkins.
    view abstract10.1097/BPO.0b013e3181cf13e6
  • Fatal outcome of a disseminated dual infection with drug-resistant Mycoplasma hominis and Ureaplasma parvum originating from a septic arthritis in an immunocompromised patient
    MacKenzie, C.R. and Nischik, N. and Kram, R. and Krauspe, R. and Jäger, M. and Henrich, B.
    International Journal of Infectious Diseases 14 (2010)
    Mycoplasma hominis and Ureaplasma parvum are rare causes of severe and fatal infections. The diagnosis of infection with mycoplasma is dependent on clinical suspicion and microbiological diagnosis, and often relies on molecular methods that do not readily detect antibiotic resistance. This may be of increasing importance as illustrated in the case below. © 2010 International Society for Infectious Diseases.
    view abstract10.1016/j.ijid.2010.02.2253
  • Initial increased wear debris of XLPE-Al2O3 bearing in total hip arthroplasties
    Jäger, M. and Behringer, M. and Zilkens, C. and Matheney, T. and Krauspe, R.
    Archives of Orthopaedic and Trauma Surgery 130 (2010)
    Introduction: Aseptic implant loosening caused by wear debris is a common reason for early implant failure after total hip replacement (THR). Materials and methods: We prospectively studied 96 patients (110 hips), 48 men and 48 women (mean age 46.8 years, mean body mass index 26.1) who had undergone cementless THR (titanium stem, press-fit cup, Al2O3 ball, XLPE liner) at a mean of 17.4 months (SD 13.4). Results: The semi-computerized evaluation of wear rate showed wear of 0.25 mm (SD 0.3) corresponding to a volume of 97.6 mm3 (SD 121.1) during the first year. It was remarkable that the annual rate of wear was significantly lower in the second year: 0.14 mm (SD 0.1), 60.0 mm3 (SD 78.7). The implant survival rate was 100%. However, two patients underwent revision surgery. Interpretation: Good, early functionality can be achieved by a cementless THR including a modular stem and a XLPE-Al2O3 bearing system. The rate of wear debris for XLPE-Al3O2 was much higher than expected within the first year after THR. However, after the initial running-in period a significant decrease of wear was documented, suggesting a biphasic abrasion [0.38 mm (SD 0.2) within the first year vs. 0.14 mm (SD 0.1)] after the running-in-period 1 year following surgery. © Springer-Verlag 2010.
    view abstract10.1007/s00402-010-1061-z
  • Kynurenine inhibits chondrocyte proliferation and is increased in synovial fluid of patients with septic arthritis
    Lögters, T.T. and Laryea, M.D. and Jäger, M. and Schädel-Höpfner, M. and Windolf, J. and Flohé, S. and Altrichter, J. and Scholz, M. and Paunel-Görgülü, A.N.
    Journal of Orthopaedic Research 28 (2010)
    Kynurenine, the major degradation product of tryptophan has been shown to directly damage various tissues. Its potential contribution to septic arthritis is unknown. In this study, we analyzed the putative diagnostic value of kynurenine for bacterial joint infection and its potential harmful effects on cartilage. In a prospective study 41 patients with a joint effusion who had undergone arthrocentesis were included. Tryptophan and kynurenine levels from synovial fluid were quantified by HPLC. Diagnostic value of kynurenine was evaluated and its effects on the proliferation of the chondrocyte cell line ATDC5 were determined. Synovial fluid kynurenine values from patients with septic arthritis (4.1 ± 0.8 μmol/L, n = 9) were significantly increased compared to patients with non-infectious inflammatory arthropathy (1.8 ± 0.2 μmol/L, n = 17) or osteoarthritis (1.2 ± 0.1 μmol/L, n = 15, p < 0.01). At a cut-off value of 2.28 μmol/L kynurenine had a sensitivity of 0.89 and a specificity of 0.87. Further, kynurenine inhibited chondrocyte (ATDC5) cell proliferation in a dose-dependent manner. Septic arthritis is associated with significantly increased values of synovial kynurenine. Furthermore kynurenine inhibits proliferation of chondrocytes, which strongly suggests a pathophysiological effect of kynurenine on cartilage in inflammatory arthropathies. © 2010 Orthopaedic Research Society.
    view abstract10.1002/jor.21158
  • MRI morphometry, cartilage damage and impaired function in the follow-up after slipped capital femoral epiphysis
    Miese, F.R. and Zilkens, C. and Holstein, A. and Bittersohl, B. and Kröpil, P. and Jäger, M. and Mamisch, T.C. and Krauspe, R. and Mödder, U. and Fürst, G.
    Skeletal Radiology 39 (2010)
    Objective To assess rotation deficits, asphericity of the femoral head and localisation of cartilage damage in the follow-up after slipped capital femoral epiphysis (SCFE). Materials and Methods Magnetic resonance imaging studies were obtained in adult patients with a history of SCFE. A total of 35 hips after SCFE in 26 patients (mean age 24.1±6.5, mean follow-up 11.9±6.1 years) were evaluated. The control group comprised 20 healthy hips from 10 young adults with an average age of 23.9±3.7 years. The MR protocol included a T1-weighted sequence with a 3D olumetric interpolated breath-hold sequence and a radial 2D proton density-weighted sequence around the femoral neck. Images were evaluated for alpha angle and cartilage damage in five positions around the femoral head. Hip function was evaluated at the time of MRI and correlated with MRI results. Mann-Whitney U test and Spearman's correlation coefficient were used for statistical analysis. Results In the hips after SCFE alpha angles were significantly increased in the anterosuperior (74.1°±18.8°) and superior (72.5°±21.5°) positions and decreased in the posterior position (25.0°±7.2°). Cartilage damage was dominant in the anterosuperior and superior positions. Impaired rotation significantly correlated with increased anterosuperior, superior and posterosuperior alpha angles. Conclusion The data support an anterosuperior and superior cam-type deformity of the femoral head-neck junction in the follow-up after SCFE. MRI after SCFE can be used to assess anterosuperior and superior alpha angles, since the anterior alpha angle by itself may underestimate asphericity and is not associated with rotation deficits. © ISS 2010.
    view abstract10.1007/s00256-010-0903-7
  • Platelet-rich plasma on calcium phosphate granules promotes metaphyseal bone healing in mini-pigs
    Jungbluth, P. and Wild, M. and Grassmann, J.-P. and Ar, E. and Sager, M. and Herten, M. and Jäger, M. and Becker, J. and Windolf, J. and Hakimi, M.
    Journal of Orthopaedic Research 28 (2010)
    The role of platelet-rich plasma (PRP) as a promoter of bone healing remains controversial. The aim of this study was to investigate the effect of PRP in combination with calcium phosphate granules (CPG) on bone defect healing in a metaphyseal long bone defect. A metaphyseal bone defect at the proximal tibia of 16 mini-pigs was filled with CPG combined with autologous PRP or CPG solely (control group). The PRP showed 4.4-fold more platelets compared to peripheral blood. Six weeks after surgery the radiological and histomorphometrical evaluations showed significantly more bone formation in the PRP group in the central area of the defect zone (p < 0.01) as well as the cortical defect zone (p < 0.04). Furthermore, the resorption rate of CPG was increased in animals who received PRP. Nevertheless there were only isolated instances of complete osseous bridging of the bone defects even in the PRP group. This study demonstrates that a PRP-CPG composit promotes bone regeneration but does not lead to a solid fusion of a tibial defect in mini-pigs. © 2010 Orthopaedic Research Society.
    view abstract10.1002/jor.21152
  • Slipped capital femoral epiphysis
    Zilkens, C. and Jäger, M. and Bittersohl, B. and Kim, Y.-J. and Millis, M.B. and Krauspe, R.
    Orthopade 39 (2010)
    Slipped capital femoral epiphysis (SCFE) is a common hip disorder in adolescence and should be diagnosed and treated surgically as soon as possible. The etiology, biomechanical, biochemical and hereditary factors are still under investigation. The classification of SCFE is based on the acuteness, clinical and radiomorphological findings. Avascular necrosis of the epiphysis (AVN) and chondrolysis occur more often in operated than in non-operated patients. Medium and long-term sequelae of SCFE are loss of function and degenerative joint disease due to femoroacetabular impingement (FAI) or consequences from complications such as AVN and chondrolysis. For mild slips the long-term prognosis is better than for moderate or severe slips. Higher grade unstable SCFE may benefit from reduction while in chronic slips corrective osteotomy may be indicated. Traditional osteotomy procedures, such as Imhäuser or Southwick intertrochanteric osteotomy are safe procedures but correct the deformity distant from the site of the deformity. The surgical dislocation with modified Dunn osteotomy according to Ganz allows the preparation of an extended retinacular soft tissue flap and offers an extensive subperiosteal exposure of the circumference of the femoral neck before reducing the slipped epiphysis anatomically. In cases of FAI due to mild deformities restoration of the head-neck offset via hip arthroscopy or surgical dislocation should be considered before higher grade cartilage damage occurs. © 2010 Springer-Verlag.
    view abstract10.1007/s00132-010-1659-4
  • cell proliferation

  • nuclear magnetic resonance

  • osteolysis

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