@phdthesis{Woerner2012,
  author    = {W{\"o}rner, Anne Eva},
  title     = {Langzeitbetreuung von Kindern und Jugendlichen mit Erkrankungen aus dem rheumatischen Formenkreis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85008},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2012},
  abstract  = {Die juvenilen rheumatischen Erkrankungen sind h{\"a}ufiger, als von Laien angenommen wird. In der vorliegenden Studie werden Patienten der Kinderklinik und Polyklinik der Universit{\"a}t W{\"u}rzburg genauer betrachtet um m{\"o}gliche Verlaufsparameter retrospektiv auswerten zu k{\"o}nnen. Es zeigt sich, dass weibliche Patienten als h{\"a}ufiger von JIA-Erkrankungen betroffene l{\"a}nger therapiert wurden als die m{\"a}nnlichen Patienten. Dabei erhielten sie l{\"a}nger NSAR und Steroide sowie h{\"a}ufiger MTX. Die Wahrscheinlichkeit eine Remission zu erreichen war im untersuchten Kollektiv nicht per se vom Geschlecht abh{\"a}ngig, jedoch gesch{\"a}tzt nach Kaplan und Meier zu Ungunsten der M{\"a}dchen, wie laut Literatur zu erwarten. Nicht best{\"a}tigen ließ sich ein negativer Zusammenhang zwischen erh{\"o}hten Entz{\"u}ndungswerten zu Beginn der Erkrankung und einer Remission im Verlauf. Weiterhin nicht best{\"a}tigen ließ sich eine generell geringere Remissionswahrscheinlichkeit bei Polyarthritis. Als pr{\"a}diktive Marker f{\"u}r eine h{\"a}ufigere Remission k{\"o}nnen nach unseren Ergebnissen nun theoretisch das m{\"a}nnliche Geschlecht (nach Kaplan und Meier) sowie erh{\"o}hte Entz{\"u}ndungswerte zu Beginn der Erkrankung angenommen werden. Wobei eine Remission h{\"a}ufiger auftrat, je schneller nach Krankheitsbeginn der Patient „an der richtigen Adresse" vorgestellt wurde.},
  subject      = {EOPA-JIA},
  language  = {de}
}
@article{KleinertTonyKrauseetal.2012,
  author    = {Kleinert, Stefan and Tony, Hans-Peter and Krause, Andreas and Feuchtenberger, Martin and Wassenberg, Siegfried and Richter, Constanze and R{\"a}ther, Ekkehard and Spieler, Wolfgang and Gnann, Holger and Wittig, Bianca M.},
  title     = {Impact of patient and disease characteristics on therapeutic success during adalimumab treatment of patients with rheumatoid arthritis: data from a German noninterventional observational study},
  series = {Rheumatology International},
  volume    = {32},
  journal   = {Rheumatology International},
  number    = {9},
  doi       = {10.1007/s00296-011-2033-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125118},
  pages     = {2759-2767},
  year      = {2012},
  abstract  = {The objective of this study was to use data from a noninterventional study to evaluate the effectiveness of adalimumab in rheumatoid arthritis (RA) patients during routine clinical practice and to explore the potential impact of patient and disease characteristics in response to adalimumab therapy. A total of 2,625 RA patients with specified data at baseline (prior to initiating adalimumab treatment) and 12 months entered this study between April 2003 and March 2009. We evaluated response to adalimumab therapy and conducted stepwise regression and subgroup analyses of factors influencing therapeutic response. During the 1-year adalimumab treatment period, disease activity decreased from a baseline mean disease activity score-28 joints (DAS28) of 5.9-3.9, while functional capacity improved from 59.0 to 68.4 Funktionsfragebogen Hannover (FFbH) percentage points. In multivariate regression models, high baseline DAS28 was the strongest positive predictor for decrease in disease activity, and high baseline functional capacity was associated with reduced gains in functional capacity. Male gender was a positive predictor of therapeutic response for both disease activity and functional capacity, while older age and multiple previous biologics were associated with a reduced therapeutic response. Subset analyses provided further support for the impact of baseline DAS28, FFbH, and prior biologic therapy on therapeutic response during treatment. We conclude that treatment with adalimumab leads to decreased disease activity and improved function during routine clinical practice. Patients with high disease activity and low functional capacity are particularly benefitted by adalimumab therapy.},
  language  = {en}
}
@article{HeiligFaerberPauletal.2022,
  author    = {Heilig, Philipp and Faerber, Lars-Christopher and Paul, Mila M. and Kupczyk, Eva and Meffert, Rainer H. and Jordan, Martin C. and Hoelscher-Doht, Stefanie},
  title     = {Plate osteosynthesis combined with bone cement provides the highest stability for tibial head depression fractures under high loading conditions},
  series = {Scientific Reports},
  volume    = {12},
  journal   = {Scientific Reports},
  number    = {1},
  doi       = {10.1038/s41598-022-19107-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299782},
  year      = {2022},
  abstract  = {Older patients sustaining tibial head depression fractures often cannot follow the post-operative rehabilitation protocols with partial weight-bearing of the affected limb, leading to osteosynthesis failure, cartilage step-off and arthritis development. Therefore, the aim of this study was to analyse the biomechanical performance of different types of osteosyntheses alone and in combination with bone cement simulating cyclically high loading conditions of tibial head depression fractures. Lateral tibial head depression fractures (AO: 41-B2.2; Schatzker type III) were created in synthetic bones and stabilized using three different osteosyntheses alone and in combination with a commonly used bone cement (chronOS™): 2 screws, 4 screws in the jail technique and a lateral angle-stable buttress plate. After fixation, the lateral tibial plateau was axially loaded in two, from each other independent testing series: In the first test protocol, 5000 cycles with 500 N and in the end load-to-failure tests were performed. In the second test protocol, the cyclic loading was increased to 1000 N. Parameters of interest were the displacement of the articular fracture fragment, the stiffness and the maximum load. The osteosyntheses revealed a higher stiffness in combination with bone cement compared to the same type of osteosynthesis alone (e.g., 500 N level: 2 screws 383 ± 43 N/mm vs. 2 screws + chronOs 520 ± 108 N/mm, increase by 36\%, p < 0.01; 4 screws 368 ± 97 N/mm vs. 4 screws + chronOS 516 ± 109 N/mm, increase by 40\%, p < 0.01; plate: 509 ± 73 N/mm vs. plate + chronOs 792 ± 150 N/mm, increase by 56\%, p < 0.01). Bone cement reduced the displacement of the plate significantly (500 N level: plate: 8.9 ± 2.8 mm vs. plate + chronOs: 3.1 ± 1.4 mm, reduction by 65\%, p < 0.01; 1000 N level: 16.9 ± 3.6 mm vs 5.6 ± 1.3 mm, reduction by 67\%, p < 0.01). Thus, the highest stiffness and lowest displacement values were found when using the plate with bone cement in both loading conditions (500 N level: 2 screws + chronOs 3.7 ± 1.3 mm, 4 screws + chronOs 6.2 ± 2.4 mm; 1000 N level: 2 screws + chronOs 6.5 ± 1.2 mm, 4 screws + chronOs 5.7 ± 0.8 mm). From a biomechanical perspective, plate osteosynthesis of tibial head depression fractures should always be combined with bone cement, provides higher stability than 2-screw and 4-screw fixation and is a valid treatment option in cases where extraordinary stability is required.},
  language  = {en}
}
@article{FuchsHeiligMcDonoghetal.2020,
  author    = {Fuchs, Konrad F. and Heilig, Philipp and McDonogh, Miriam and Boelch, Sebastian and Gbureck, Uwe and Meffert, Rainer H. and Hoelscher-Doht, Stefanie and Jordan, Martin C.},
  title     = {Cement-augmented screw fixation for calcaneal fracture treatment: a biomechanical study comparing two injectable bone substitutes},
  series = {Journal of Orthopaedic Surgery and Research},
  volume    = {15},
  journal   = {Journal of Orthopaedic Surgery and Research},
  doi       = {10.1186/s13018-020-02009-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230336},
  year      = {2020},
  abstract  = {Background The role of cement-augmented screw fixation for calcaneal fracture treatment remains unclear. Therefore, this study was performed to biomechanically analyze screw osteosynthesis by reinforcement with either a calcium phosphate (CP)-based or polymethylmethacrylate (PMMA)-based injectable bone cement. Methods A calcaneal fracture (Sanders type IIA) including a central cancellous bone defect was generated in 27 synthetic bones, and the specimens were assigned to 3 groups. The first group was fixed with four screws (3.5 mm and 6.5 mm), the second group with screws and CP-based cement (Graftys (R) QuickSet; Graftys, Aix-en-Provence, France), and the third group with screws and PMMA-based cement (Traumacem (TM) V+; DePuy Synthes, Warsaw, IN, USA). Biomechanical testing was conducted to analyze peak-to-peak displacement, total displacement, and stiffness in following a standardized protocol. Results The peak-to-peak displacement under a 200-N load was not significantly different among the groups; however, peak-to-peak displacement under a 600- and 1000-N load as well as total displacement exhibited better stability in PMMA-augmented screw osteosynthesis compared to screw fixation without augmentation. The stiffness of the construct was increased by both CP- and PMMA-based cements. Conclusion Addition of an injectable bone cement to screw osteosynthesis is able to increase fixation strength in a biomechanical calcaneal fracture model with synthetic bones. In such cases, PMMA-based cements are more effective than CP-based cements because of their inherently higher compressive strength. However, whether this high strength is required in the clinical setting for early weight-bearing remains controversial, and the non-degradable properties of PMMA might cause difficulties during subsequent interventions in younger patients.},
  language  = {en}
}
@article{ArmbrusterKriegWeissenbergeretal.2017,
  author    = {Armbruster, Nicole and Krieg, Jennifer and Weißenberger, Manuel and Scheller, Carsten and Steinert, Andre F.},
  title     = {Rescued Chondrogenesis of Mesenchymal Stem Cells under Interleukin 1 Challenge by Foamyviral Interleukin 1 Receptor Antagonist Gene Transfer},
  series = {Frontiers in Pharmacology},
  volume    = {8},
  journal   = {Frontiers in Pharmacology},
  number    = {255},
  doi       = {10.3389/fphar.2017.00255},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170919},
  year      = {2017},
  abstract  = {Background: Mesenchymal stem cells (MSCs) and their chondrogenic differentiation have been extensively investigated in vitro as MSCs provide an attractive source besides chondrocytes for cartilage repair therapies. Here we established prototype foamyviral vectors (FVV) that are derived from apathogenic parent viruses and are characterized by a broad host range and a favorable integration pattern into the cellular genome. As the inflammatory cytokine interleukin 1 beta (IL1β) is frequently present in diseased joints, the protective effects of FVV expressing the human interleukin 1 receptor antagonist protein (IL1RA) were studied in an established in vitro model (aggregate culture system) of chondrogenesis in the presence of IL1β. Materials and Methods: We generated different recombinant FVVs encoding enhanced green fluorescent protein (EGFP) or IL1RA and examined their transduction efficiencies and transgene expression profiles using different cell lines and human primary MSCs derived from bone marrow-aspirates. Transgene expression was evaluated by fluorescence microscopy (EGFP), flow cytometry (EGFP), and ELISA (IL1RA). For evaluation of the functionality of the IL1RA transgene to block the inhibitory effects of IL1β on chondrogenesis of primary MSCs and an immortalized MSC cell line (TERT4 cells), the cells were maintained following transduction as aggregate cultures in standard chondrogenic media in the presence or absence of IL1β. After 3 weeks of culture, pellets were harvested and analyzed by histology and immunohistochemistry for chondrogenic phenotypes. Results: The different FVV efficiently transduced cell lines as well as primary MSCs, thereby reaching high transgene expression levels in 6-well plates with levels of around 100 ng/ml IL1RA. MSC aggregate cultures which were maintained in chondrogenic media without IL1β supplementation revealed a chondrogenic phenotype by means of strong positive staining for collagen type II and matrix proteoglycan (Alcian blue). Addition of IL1β was inhibitory to chondrogenesis in untreated control pellets. In contrast, foamyviral mediated IL1RA expression rescued the chondrogenesis in pellets cultured in the presence of IL1β. Transduced MSC pellets reached thereby very high IL1RA transgene expression levels with a peak of 1087 ng/ml after day 7, followed by a decrease to 194 ng/ml after day 21, while IL1RA concentrations of controls were permanently below 200 pg/ml. Conclusion: Our results indicate that FVV are capable of efficient gene transfer to MSCs, while reaching IL1RA transgene expression levels, that were able to efficiently block the impacts of IL1β in vitro. FVV merit further investigation as a means to study the potential as a gene transfer tool for MSC based therapies for cartilage repair.},
  language  = {en}
}