@article{BaumbachHoertererOppeltetal.2022, author = {Baumbach, Sebastian Felix and H{\"o}rterer, Hubert and Oppelt, Sonja and Szeimies, Ulrike and Polzer, Hans and Walther, Markus}, title = {Do pre-operative radiologic assessment predict postoperative outcomes in patients with insertional Achilles tendinopathy?: a retrospective database study}, series = {Archives of Orthopaedic and Trauma Surgery}, volume = {142}, journal = {Archives of Orthopaedic and Trauma Surgery}, number = {11}, issn = {1434-3916}, doi = {10.1007/s00402-021-03897-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307963}, pages = {3045-3052}, year = {2022}, abstract = {Introduction Diagnosis and treatment of insertional tendinopathy of the Achilles tendon (IAT) remains a challenge. The aim of this study was to assess the influence of pre-operative radiological pathologies on the patient-reported outcomes following open debridement of all pathologies for IAT. Materials and methods In this IRB-approved retrospective correlation and comparative study, patients with pre-operative imaging were identified from the authors' retrospective IAT database comprising of 118 patients. All were treated by a standardized surgical treatment strategy utilizing a midline, transachillary approach and debridement of all pathologies. A total of fifteen radiologic parameters were measured on radiographs (RX) and MRI. The patient-reported outcomes were assessed using the Victorian Institute of Sport Assessment-Achilles questionnaire (VISA-A-G) and the general health questionnaire SF-12 at a minimum follow-up of 12 months. The data are presented as mean ± SD (95\% CI). Results 88 patients (74.6\%) with an average age of 50 ± 12 (47-52) years were included. Radiographs were available in 68 patients and MRI in 53. The mean follow-up was 3.8 ± 1.9 (3.4-4.3) years. The overall VISA-A-G was 81 ± 22 (77-86), the SF-12 PCS 54 ± 7 (52-55), and the SF-12 MCS 52 ± 9 (50-54) points. None of the assessed radiological parameters had a significant influence on the patient-reported outcome following surgical treatment for IAT. Conclusion In this retrospective correlation study, no significant association was found between preoperative radiographic and MRI radiologic parameters for IAT and postoperative patient-reported outcomes (VISA-A-G and SF-12).}, language = {en} } @phdthesis{Keicher2024, author = {Keicher, Franca}, title = {Muskul{\"a}re Einfl{\"u}sse der Rotatorenmanschette auf die Early Onset Arthrose der Schulter}, doi = {10.25972/OPUS-36055}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360557}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {Introduction: The etiology of early onset shoulder arthritis (EOA) remains unclear. Due to the influence of the muscles of the rotator cuff (RC) on glenohumeral kinematics, muscular causes are being discussed. The aim of the study was to identify corresponding factors on EOA based on volume measurements of the RC and examinations of the adjacent bony structures in MRI imaging, as well as the collection of patient-specific characteristics. Methods: In a case-control study, shoulders of 15 patients (14 men, 1 woman) with shoulder arthritis before the age of 60 and 13 control subjects (13 men) were examined. Anthropometric body measurements and clinical characteristics were collected. The volumes of the RC were calculated using manual tracing of the individual muscle cross- sections on MRI scans. In addition, the angles between the coracoid or scapular spine and scapular body were measured. The position of the scapula to the thorax was determined by recording the angle of the scapula to the plane of the table. The glenoid retroversion, morphological types, and humeral head subluxation were also collected. The analysis was conducted using descriptive and comparative statistical methods, as well as logistic and linear regression analyses. Results: The volumes of the RC did not differ significantly between the patients with EOA and the control subjects, either in absolute terms or in relative proportions. However, significantly higher values of thorax circumference and diameter, body weight, and BMI were found in the diseased individuals compared to the controls. Furthermore, these individuals were significantly more likely to have occupations that expended more than 1400 kcal per day. The risk of EOA increased with the steeper angle of the scapula to the thorax. Patients with B2-glenoid had significantly larger angles between the coracoid and scapular body as well as higher values of transverse thorax diameter, than those with B1-glenoid. Regardless of whether EOA was present or not, engaging in overhead sports was associated with a higher subluxation index. Conclusion: While the RC did not show any abnormalities in EOA patients, male gender, BMI, thoracic shape and scapular position, as well as certain occupations and sports, were associated with EOA. Further studies are needed to investigate these risk factors in EOA more precisely and develop possible treatment concepts. Peripheral shoulder muscles (such as teres major or pectoralis major) should also be included in the investigations.}, subject = {Arthrose}, language = {de} } @article{WeissenbergerWagenbrennerNickeletal.2023, author = {Weißenberger, Manuel and Wagenbrenner, Mike and Nickel, Joachim and Ahlbrecht, Rasmus and Blunk, Torsten and Steinert, Andre F. and Gilbert, Fabian}, title = {Comparative in vitro treatment of mesenchymal stromal cells with GDF-5 and R57A induces chondrogenic differentiation while limiting chondrogenic hypertrophy}, series = {Journal of Experimental Orthopaedics}, volume = {10}, journal = {Journal of Experimental Orthopaedics}, doi = {10.1186/s40634-023-00594-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357770}, year = {2023}, abstract = {Purpose Hypertrophic cartilage is an important characteristic of osteoarthritis and can often be found in patients suffering from osteoarthritis. Although the exact pathomechanism remains poorly understood, hypertrophic de-differentiation of chondrocytes also poses a major challenge in the cell-based repair of hyaline cartilage using mesenchymal stromal cells (MSCs). While different members of the transforming growth factor beta (TGF-β) family have been shown to promote chondrogenesis in MSCs, the transition into a hypertrophic phenotype remains a problem. To further examine this topic we compared the effects of the transcription growth and differentiation factor 5 (GDF-5) and the mutant R57A on in vitro chondrogenesis in MSCs. Methods Bone marrow-derived MSCs (BMSCs) were placed in pellet culture and in-cubated in chondrogenic differentiation medium containing R57A, GDF-5 and TGF-ß1 for 21 days. Chondrogenesis was examined histologically, immunohistochemically, through biochemical assays and by RT-qPCR regarding the expression of chondrogenic marker genes. Results Treatment of BMSCs with R57A led to a dose dependent induction of chondrogenesis in BMSCs. Biochemical assays also showed an elevated glycosaminoglycan (GAG) content and expression of chondrogenic marker genes in corresponding pellets. While treatment with R57A led to superior chondrogenic differentiation compared to treatment with the GDF-5 wild type and similar levels compared to incubation with TGF-ß1, levels of chondrogenic hypertrophy were lower after induction with R57A and the GDF-5 wild type. Conclusions R57A is a stronger inducer of chondrogenesis in BMSCs than the GDF-5 wild type while leading to lower levels of chondrogenic hypertrophy in comparison with TGF-ß1.}, language = {en} } @article{HeinzMellerLuetkensetal.2023, author = {Heinz, Tizian and Meller, Felix and Luetkens, Karsten Sebastian and Anderson, Philip Mark and Stratos, Ioannis and Horas, Konstantin and Rudert, Maximilian and Reppenhagen, Stephan and Weißenberger, Manuel}, title = {The AMADEUS score is not a sufficient predictor for functional outcome after high tibial osteotomy}, series = {Journal of Experimental Orthopaedics}, volume = {10}, journal = {Journal of Experimental Orthopaedics}, doi = {10.1186/s40634-023-00575-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357765}, year = {2023}, abstract = {Purpose The Area Measurement And Depth Underlying Structures (AMADEUS) classification system has been proposed as a valuable tool for magnetic resonance (MR)-based grading of preoperatively encountered chondral defects of the knee joint. However, the potential relationship of this novel score with clinical data was yet to determine. It was the primary intention of this study to assess the correlative relationship of the AMADEUS with patient reported outcome scores in patients undergoing medial open-wedge high tibial valgus osteotomy (HTO). Furthermore, the arthroscopic ICRS (International Cartilage Repair Society) grade evaluation was tested for correlation with the AMADEUS classification system. Methods This retrospective, monocentric study found a total of 70 individuals that were indicated for HTO due to degenerative chondral defects of the medial compartment between 2008 and 2019. A preoperative MR image as well as a pre-osteotomy diagnostic arthroscopy for ICRS grade evaluation was mandatory for all patients. The Knee Osteoarthritis Outcome Score (KOOS) including its five subscale scores (KOOS-ADL, KOOS-QOL, KOOS-Sports, KOOS-Pain, KOOS-Symptoms) was obtained preoperatively and at a mean follow-up of 41.2 ± 26.3 months. Preoperative chondral defects were evaluated using the AMADEUS classification system and the final AMADEUS scores were correlated with the pre- and postoperative KOOS subscale sores. Furthermore, arthroscopic ICRS defect severity was correlated with the AMADEUS classification system. Results There was a statistically significant correlation between the AMADEUS BME (bone marrow edema) subscore and the KOOS Symptoms subscore at the preoperative visit (r = 0.25, p = 0.04). No statistically significant monotonic association between the AMADEUS total score and the AMADEUS grade with pre- and postoperative KOOS subscale scores were found. Intraoperatively obtained ICRS grade did reveal a moderate correlative relation with the AMADEUS total score and the AMADEUS grade (r = 0.28, p = 0.02). Conclusions The novel AMADEUS classification system largely lacks correlative capacity with patient reported outcome measures in patients undergoing HTO. The MR tomographic appearance of bone marrow edema is the only parameter predictive of the clinical outcome at the preoperative visit.}, language = {en} } @article{MunawarZhouPrommersbergeretal.2023, author = {Munawar, Umair and Zhou, Xiang and Prommersberger, Sabrina and Nerreter, Silvia and Vogt, Cornelia and Steinhardt, Maximilian J. and Truger, Marietta and Mersi, Julia and Teufel, Eva and Han, Seungbin and Haertle, Larissa and Banholzer, Nicole and Eiring, Patrick and Danhof, Sophia and Navarro-Aguadero, Miguel Angel and Fernandez-Martin, Adrian and Ortiz-Ruiz, Alejandra and Barrio, Santiago and Gallardo, Miguel and Valeri, Antonio and Castellano, Eva and Raab, Peter and Rudert, Maximilian and Haferlach, Claudia and Sauer, Markus and Hudecek, Michael and Martinez-Lopez, J. and Waldschmidt, Johannes and Einsele, Hermann and Rasche, Leo and Kort{\"u}m, K. Martin}, title = {Impaired FADD/BID signaling mediates cross-resistance to immunotherapy in Multiple Myeloma}, series = {Communications Biology}, volume = {6}, journal = {Communications Biology}, doi = {10.1038/s42003-023-05683-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357609}, year = {2023}, abstract = {The treatment landscape in multiple myeloma (MM) is shifting from genotoxic drugs to immunotherapies. Monoclonal antibodies, immunoconjugates, T-cell engaging antibodies and CART cells have been incorporated into routine treatment algorithms, resulting in improved response rates. Nevertheless, patients continue to relapse and the underlying mechanisms of resistance remain poorly understood. While Impaired death receptor signaling has been reported to mediate resistance to CART in acute lymphoblastic leukemia, this mechanism yet remains to be elucidated in context of novel immunotherapies for MM. Here, we describe impaired death receptor signaling as a novel mechanism of resistance to T-cell mediated immunotherapies in MM. This resistance seems exclusive to novel immunotherapies while sensitivity to conventional anti-tumor therapies being preserved in vitro. As a proof of concept, we present a confirmatory clinical case indicating that the FADD/BID axis is required for meaningful responses to novel immunotherapies thus we report impaired death receptor signaling as a novel resistance mechanism to T-cell mediated immunotherapy in MM.}, language = {en} } @article{MaichlKirnerBecketal.2023, author = {Maichl, Daniela Simone and Kirner, Julius Arthur and Beck, Susanne and Cheng, Wen-Hui and Krug, Melanie and Kuric, Martin and Ade, Carsten Patrick and Bischler, Thorsten and Jakob, Franz and Hose, Dirk and Seckinger, Anja and Ebert, Regina and Jundt, Franziska}, title = {Identification of NOTCH-driven matrisome-associated genes as prognostic indicators of multiple myeloma patient survival}, series = {Blood Cancer Journal}, volume = {13}, journal = {Blood Cancer Journal}, doi = {10.1038/s41408-023-00907-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357598}, year = {2023}, abstract = {No abstract available.}, language = {en} } @article{ReppenhagenBeckerKugleretal.2023, author = {Reppenhagen, Stephan and Becker, Roland and Kugler, Andreas and John, Dominik and Kopf, Sebastian and Anetzberger, Hermann}, title = {Hand dominance is not of significance in performing fundamental arthroscopic skills simulation training tasks}, series = {Arthroscopy, Sports Medicine, and Rehabilitation}, volume = {5}, journal = {Arthroscopy, Sports Medicine, and Rehabilitation}, number = {5}, issn = {2666-061X}, doi = {10.1016/j.asmr.2023.100767}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350432}, year = {2023}, abstract = {Purpose To compare the performance of the dominant and nondominant hand during fundamental arthroscopic simulator training. Methods Surgical trainees who participated in a 2-day simulator training course between 2021 and 2023 were classified, according to their arthroscopic experience in beginners and competents. Only right-handed individuals with complete data sets were included in the study. Ambidexterity was trained using a box trainer (Fundamentals of Arthroscopic Surgery Training, Virtamed AG, Schlieren, Switzerland).Two tasks, periscoping for learning camera guidance and triangulation for additional instrument handling, were performed 4 times with the camera in the dominant hand and then in the nondominant hand. For each task, exercise time, camera path length, and instrument path length were recorded and analyzed. Results Out of 94 participants 74 right-handed individuals (22 females, 52 males) were classified to novices (n = 43, less than 10 independently performed arthroscopies) and competents (n = 31, more than 10 independently performed arthroscopies). Competents performed significantly better than novices. No significant difference was found after changing the guiding hand for the camera from the dominant to the nondominant hand regarding the camera path length and the instrument path length. Notably, tasks were performed even faster when using the camera in the nondominant hand. Conclusions Our data demonstrate that the learned manual skills during basic arthroscopic training are quickly transferred to the contralateral side. In consequence, additional fundamental skills training for camera guidance and instrument handling of the nondominant hand are not necessary. Clinical Relevance For skillful arthroscopy, camera guidance and instrument handing must be equally mastered with both hands. It is important to understand how hand dominance may affect learning during arthroscopic simulator training.}, language = {en} } @article{TrivanovicVolkmannStoeckletal.2023, author = {Trivanovic, Drenka and Volkmann, Noah and Stoeckl, Magdalena and Tertel, Tobias and Rudert, Maximilian and Giebel, Bernd and Herrmann, Marietta}, title = {Enhancement of immunosuppressive activity of mesenchymal stromal cells by platelet-derived factors is accompanied by apoptotic priming}, series = {Stem Cell Reviews and Reports}, volume = {19}, journal = {Stem Cell Reviews and Reports}, number = {3}, doi = {10.1007/s12015-022-10471-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324669}, pages = {713-733}, year = {2023}, abstract = {The pro-inflammatory phase of bone healing, initiated by platelet activation and eventually hematoma formation, impacts bone marrow mesenchymal stromal cells (MSCs) in unknown ways. Here, we created platelet-rich plasma (PRP) hydrogels to study how platelet-derived factors modulate functional properties of encapsulated MSCs in comparison to a non-inflammatory fibrin (FBR) hydrogel environment. MSCs were isolated from human bone marrow, while PRP was collected from pooled apheresis thrombocyte concentrates and used for hydrogel preparation. After their encapsulation in hydrogels for 72 h, retrieved MSCs were analyzed for immunomodulatory activities, apoptosis, stem cell properties, senescence, CD9\(^+\), CD63\(^+\) and CD81\(^+\) extracellular vesicle (EV) release, and metabolism-related changes. PRP-hydrogels stimulated immunosuppressive functions of MSCs, along with their upregulated susceptibility to cell death in communication with PBMCs and augmented caspase 3/7 activity. We found impaired clonal growth and cell cycle progression, and more pronounced β-galactosidase activity as well as accumulation of LC3-II-positive vacuoles in PRP-MSCs. Stimuli derived from PRP-hydrogels upregulated AKT and reduced mTOR phosphorylation in MSCs, which suggests an initiation of survival-related processes. Our results showed that PRP-hydrogels might represent a metabolically stressful environment, inducing acidification of MSCs, reducing polarization of the mitochondrial membrane and increasing lipid accumulation. These features were not detected in FBR-MSCs, which showed reduced CD63\(^+\) and CD81\(^+\) EV production and maintained clonogenicity. Our data revealed that PRP-derived hematoma components cause metabolic adaptation of MSCs followed by increased immune regulatory functions. For the first time, we showed that PRP stimuli represent a survival challenge and "apoptotic priming" that are detrimental for stem cell-like growth of MSCs and important for their therapeutic consideration.}, language = {en} } @article{ScorcellettiKaraZangeetal.2022, author = {Scorcelletti, Matteo and Kara, Serhan and Zange, Jochen and Jordan, Jens and Semler, Oliver and Sch{\"o}nau, Eckhard and Rittweger, J{\"o}rn and Ireland, Alex and Seefried, Lothar}, title = {Lower limb bone geometry in adult individuals with X-linked hypophosphatemia: an observational study}, series = {Osteoporosis International}, volume = {33}, journal = {Osteoporosis International}, number = {7}, doi = {10.1007/s00198-022-06385-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324655}, pages = {1601-1611}, year = {2022}, abstract = {Summary We assessed lower-limb geometry in adults with X-linked hypophosphatemia (XLH) and controls. We found large differences in multiple measures including femoral and tibial torsion, bowing and cross-sectional area and acetabular version and coverage which may contribute to clinical problems such as osteoarthritis, fractures and altered gait common in XLH. Purpose Individuals with X-linked hypophosphatemia (XLH) are at risk of lower-limb deformities and early onset of osteoarthritis. These two factors may be linked, as altered biomechanics is a risk factor for osteoarthritis. This exploratory evaluation aims at providing clues and concepts for this association to facilitate future larger-scale and longitudinal studies on that aspect. Methods For this observational study, 13 patients with XLH, aged 18-65 years (6 female), were compared with sex-, age- and weight-matched healthy individuals at a single German research centre. Femoral and hip joint geometry, including femoral and tibial torsion and femoral and tibial shaft bowing, bone cross-sectional area (CSA) and acetabular version and coverage were measured from magnetic resonance imaging (MRI) scans. Results Total femoral torsion was 29° lower in individuals with XLH than in controls (p < 0.001), mainly resulting from lower intertrochanteric torsion (ITT) (p < 0.001). Femoral lateral and frontal bowing, tibial frontal bowing, mechanical axis, femoral mechanical-anatomical angle, acetabular version and acetabular coverage were all greater and tibial torsion lower in individuals with XLH as compared to controls (all p < 0.05). Greater femoral total and marrow cavity CSA, greater tibial marrow cavity CSA and lower cortical CSA were observed in XLH (all p < 0.05). Discussion We observed large differences in clinically relevant measures of tibia and particularly femur bone geometry in individuals with XLH compared to controls. These differences may plausibly contribute to clinical manifestations of XLH such as early-onset osteoarthritis, pseudofractures and altered gait and therefore should be considered when planning corrective surgeries.}, language = {en} } @article{RakKlannHeinzetal.2023, author = {Rak, Dominik and Klann, Lukas and Heinz, Tizian and Anderson, Philip and Stratos, Ioannis and Nedopil, Alexander J. and Rudert, Maximilian}, title = {Influence of mechanical alignment on functional knee phenotypes and clinical outcomes in primary TKA: a 1-year prospective analysis}, series = {Journal of Personalized Medicine}, volume = {13}, journal = {Journal of Personalized Medicine}, number = {5}, issn = {2075-4426}, doi = {10.3390/jpm13050778}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313646}, year = {2023}, abstract = {In total knee arthroplasty (TKA), functional knee phenotypes are of interest regarding surgical alignment strategies. Functional knee phenotypes were introduced in 2019 and consist of limb, femoral, and tibial phenotypes. The hypothesis of this study was that mechanically aligned (MA) TKA changes preoperative functional phenotypes, which decreases the 1-year Forgotten Joint (FJS) and Oxford Knee Score (OKS) and increases the 1-year WOMAC. All patients included in this study had end-stage osteoarthritis and were treated with a primary MA TKA, which was supervised by four academic knee arthroplasty specialists. To determine the limb, femoral, and tibial phenotype, a long-leg radiograph (LLR) was imaged preoperatively and two to three days after TKA. FJS, OKS, and WOMAC were obtained 1 year after TKA. Patients were categorized using the change in functional limb, femoral, and tibial phenotype measured on LLR, and the scores were compared between the different categories. A complete dataset of preoperative and postoperative scores and radiographic images could be obtained for 59 patients. 42\% of these patients had a change of limb phenotype, 41\% a change of femoral phenotype, and 24\% a change of tibial phenotype of more than ±1 relative to the preoperative phenotype. Patients with more than ±1 change of limb phenotype had significantly lower median FJS (27 points) and OKS (31 points) and higher WOMAC scores (30 points) relative to the 59-, 41-, and 4-point scores of those with a 0 ± 1 change (p < 0.0001 to 0.0048). Patients with a more than ±1 change of femoral phenotype had significantly lower median FJS (28 points) and OKS (32 points) and higher WOMAC scores (24 points) relative to the 69-, 40-, and 8-point scores of those with a 0 ± 1 change (p < 0.0001). A change in tibial phenotype had no effect on the FJS, OKS, and WOMAC scores. Surgeons performing MA TKA could consider limiting coronal alignment corrections of the limb and femoral joint line to within one phenotype to reduce the risk of low patient-reported satisfaction and function at 1-year.}, language = {en} } @article{WeberBeckKlugetal.2023, author = {Weber, Patrick and Beck, Melina and Klug, Michael and Klug, Andreas and Klug, Alexander and Glowalla, Claudio and Gollwitzer, Hans}, title = {Survival of patient-specific unicondylar knee replacement}, series = {Journal of Personalized Medicine}, volume = {13}, journal = {Journal of Personalized Medicine}, number = {4}, issn = {2075-4426}, doi = {10.3390/jpm13040665}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313650}, year = {2023}, abstract = {Unicompartmental knee arthroplasty (UKA) in isolated medial or lateral osteoarthritis leads to good clinical results. However, revision rates are higher in comparison to total knee arthroplasty (TKA). One reason is suboptimal fitting of conventional off-the-shelf prostheses, and major overhang of the tibial component over the bone has been reported in up to 20\% of cases. In this retrospective study, a total of 537 patient-specific UKAs (507 medial prostheses and 30 lateral prostheses) that had been implanted in 3 centers over a period of 10 years were analyzed for survival, with a minimal follow-up of 1 year (range 12 to 129 months). Furthermore, fitting of the UKAs was analyzed on postoperative X-rays, and tibial overhang was quantified. A total of 512 prostheses were available for follow-up (95.3\%). Overall survival rate (medial and lateral) of the prostheses after 5 years was 96\%. The 30 lateral UKAs showed a survival rate of 100\% at 5 years. The tibial overhang of the prosthesis was smaller than 1 mm in 99\% of cases. In comparison to the reported results in the literature, our data suggest that the patient-specific implant design used in this study is associated with an excellent midterm survival rate, particularly in the lateral knee compartment, and confirms excellent fitting.}, language = {en} } @article{HoertererBaumbachLemperleetal.2019, author = {H{\"o}rterer, Hubert and Baumbach, Sebastian Felix and Lemperle, Stefan and Altenberger, Sebastian and Gottschalk, Oliver and Mehlhorn, Alexander Tobias and R{\"o}ser, Anke and Walther, Markus}, title = {Clinical outcome and concomitant injuries in operatively treated fractures of the lateral process of the talus}, series = {BMC Musculoskeletal Disorders}, volume = {20}, journal = {BMC Musculoskeletal Disorders}, doi = {10.1186/s12891-019-2603-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-321207}, year = {2019}, abstract = {Background The aim of this study was to review the patient rated outcome (PROM) of surgically treated fractures to the lateral process of the talus (LPTF) and identify factors influencing the outcome. Methods Retrospective study with a current follow-up. Eligible were all patients treated surgically for a LPTF (n = 23) with a minimum follow-up of one year. Demographics, medical history, trauma mechanism, fracture characteristics, concomitant injuries, treatment details, complications, return to work and sports were assessed retrospectively. The current follow-up included the VAS FA, Karlsson Score, and SF-12. The primary outcome was the VAS FA. Secondary aim was the identification of parameters influencing the PROMs. Results 22 patients (96\% follow-up) with a mean age of 32 ± 9 (18 to 49) years were included. 73\% suffered a Hawkins Type 1, 23\% a Type 2, and one patient a Type 3 fracture. 82\% suffered concomitant injuries. 9\% suffered minor surgical side infections, 50\% developed symptomatic subtalar osteoarthritis. At final follow-up (44 ± 2 (12 to 97) months), the mean VAS FA Overall was 77 ± 21 (20 to 100), the Karlsson Score 72 ± 21 (34 to 97), and for the SF 12 the PCS 53 ± 8 (36 to 64) and the MCS 53 ± 7 (32 to 63). 50\% of patients returned to their previous level of sports. Hawkins Type 1 fractures resulted in better VAS FA Overall score than Type 2 fractures. Posttraumatic subtalar osteoarthritis was the independent factor associated to a poor patient rated outcome (VAS FA, Karlsson Score). Conclusion After a follow-up of over 3.5 years, surgically treated LPTF resulted in only moderate results. 50\% suffered posttraumatic symptomatic subtalar osteoarthritis, which was the primary independent parameter for a poor outcome following LPTF. Level of evidence Level III.}, language = {en} } @phdthesis{Schiffmaier2024, author = {Schiffmaier, Jana}, title = {Parathormon als potentielle Therapiestrategie der Odonto-Hypophosphatasie - Untersuchungen in einem dentogenen \(in-vitro\)-Modell}, doi = {10.25972/OPUS-34915}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349152}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {Hypophosphatasie (HPP) beschreibt eine seltene Erbkrankheit, die haupts{\"a}chlich durch heterozygote Mutationen im ALPL-Gen verursacht wird. Diese f{\"u}hren zu einer verminderten Aktivit{\"a}t der gewebeunspezifischen alkalischen Phosphatase (TNAP). Neben skelettalen Symptomen sind Zahnanomalien wie der vorzeitige Verlust von Milchz{\"a}hnen ohne resorbierte Wurzel sowie eine gest{\"o}rte Mineralisierung der Zahnhart-substanzen ein typisches Merkmal der HPP. Die zugrunde liegenden molekularen Mechanismen sind bisher noch nicht vollst{\"a}ndig verstanden. In der vorliegenden Arbeit wurden Zelllinien des parodontalen Ligaments mit Mutationen im ALPL-Gen charakterisiert, um anschließend m{\"o}gliche Therapiestrategien f{\"u}r die HPP auf molekularer Ebene zu untersuchen. Im Rahmen der basalen Charakterisierung wurden die Zelllinien hinsichtlich der TNAP-Expression (Immunhistochemie, Western Blot), des Stoffwechselprofils (ATP-Assay) und des osteogenen Differenzierungspotenzials (Alizarin-F{\"a}rbung) analysiert. Von Interesse war auch, ob durch CRISPR/Cas9-basiertes Genediting Off-Target Mutationen entstanden sind. Zur Untersuchung der molekularen Auswirkungen von PTH, welches die ALPL-Expression steigern kann, wurden zwei Protokolle etabliert, die eine kontinuier-liche, kurzzeitige bzw. intermittierende Pr{\"a}senz von PTH in-vitro imitieren. Anschließend wurde die ALPL-Expression (qPCR) sowie TNAP-Aktivit{\"a}t (CSPD-Assay) ermittelt. Die basale TNAP-Expression war variabel und reichte vom v{\"o}lligen Fehlen in den Zell-linien mit Deletionen bis hin zu einer starken TNAP-Expression in der Zelllinie mit einer heterogenen Punktmutation. Eine niedrige Expression ging mit einer verringerten Zell-proliferation sowie extrazellul{\"a}ren ATP einher. Es zeigte sich ein unterschiedliches Mineralisierungspotenzial, das haupts{\"a}chlich das TNAP-Expressionsniveau in den verschiedenen Zelllinien widerspiegelt, w{\"a}hrend die PTH-Stimulation keine Wirkung auf die Differenzierung hatte. Im Gegensatz zu klinischen Beobachtungen deuten die Ergebnisse auf eine hohe Korrelation zwischen Genotyp und Ph{\"a}notyp in-vitro hin, die in-vivo noch best{\"a}tigt werden m{\"u}ssen. Die Sequenzierung best{\"a}tigte, dass durch die Geneditierung keine Off-Target Mutationen aufgetreten sind, welche somit keinen limitierenden Faktor hinsichtlich der Differenzierungskapazit{\"a}t darstellen k{\"o}nnen. Die Stimulation mit PTH f{\"u}hrte zwar nicht zu einer gesteigerten ALPL-Expression, doch konnte die TNAP-Aktivit{\"a}t in den ALPL-defizienten Zelllinien punktuell gesteigert werden und bildet somit eine solide Basis f{\"u}r weitere Experimente, die zur Therapieentwicklung f{\"u}r die Odonto-HPP beitragen k{\"o}nnen.}, subject = {Hypophosphatasie}, language = {de} } @article{EidmannKamawalLuedemannetal.2023, author = {Eidmann, Annette and Kamawal, Yama and Luedemann, Martin and Raab, Peter and Rudert, Maximilian and Stratos, Ioannis}, title = {Demographics and etiology for lower extremity amputations — experiences of an university orthopaedic center in Germany}, series = {Medicina}, volume = {59}, journal = {Medicina}, number = {2}, issn = {1648-9144}, doi = {10.3390/medicina59020200}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304856}, year = {2023}, abstract = {Background and Objectives: Currently, the worldwide incidence of major amputations in the general population is decreasing whereas the incidence of minor amputations is increasing. The purpose of our study was to analyze whether this trend is reflected among orthopaedic patients treated with lower extremity amputation in our orthopaedic university institution. Materials and Methods: We conducted a single-center retrospective study and included patients referred to our orthopaedic department for lower extremity amputation (LEA) between January 2007 and December 2019. Acquired data were the year of amputation, age, sex, level of amputation and cause of amputation. T test and Chi² test were performed to compare age and amputation rates between males and females; significance was defined as p < 0.05. Linear regression and multivariate logistic regression models were used to test time trends and to calculate probabilities for LEA. Results: A total of 114 amputations of the lower extremity were performed, of which 60.5\% were major amputations. The number of major amputations increased over time with a rate of 0.6 amputation/year. Men were significantly more often affected by LEA than women. Age of LEA for men was significantly below the age of LEA for women (men: 54.8 ± 2.8 years, women: 64.9 ± 3.2 years, p = 0.021). Main causes leading to LEA were tumors (28.9\%) and implant-associated complications (25.4\%). Implant-associated complications and age raised the probability for major amputation, whereas malformation, angiopathies and infections were more likely to cause a minor amputation. Conclusions: Among patients in our orthopaedic institution, etiology of amputations of the lower extremity is multifactorial and differs from other surgical specialties. The number of major amputations has increased continuously over the past years. Age and sex, as well as diagnosis, influence the type and level of amputation.}, language = {en} } @article{HeinzEidmannJakuscheitetal.2023, author = {Heinz, Tizian and Eidmann, Annette and Jakuscheit, Axel and Laux, Tino and Rudert, Maximilian and Stratos, Ioannis}, title = {Demographics and trends for inbound medical tourism in Germany for orthopedic patients before and during the COVID-19 pandemic}, series = {International Journal of Environmental Research and Public Health}, volume = {20}, journal = {International Journal of Environmental Research and Public Health}, number = {2}, issn = {1660-4601}, doi = {10.3390/ijerph20021209}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304955}, year = {2023}, abstract = {Medical tourism is a rapidly growing sector of economic growth and diversification. However, data on the demographics and characteristics of the traveling patients are sparse. In this study, we analyzed the common demographic properties and characteristics of the inbound medical tourists seeking orthopedic medical care in Germany for the years 2010 to 2019 compared to a domestic group. At the same time, we examined how the COVID-19 pandemic outbreak of 2020 changed the field of medical tourism in Germany. Calculations were performed using administrative hospital data provided by the Federal Statistical Department of Germany. Data were analyzed from the years 2010 to 2020. A total of six elective orthopedic surgery codes (bone biopsy, knee arthroplasty, foot surgery, osteotomy, hardware removal, and arthrodesis) were identified as key service indicators for medical tourism and further analyzed. Factors including residence, sex, year, and type of elective surgery were modeled using linear regression analysis. Age and sex distributions were compared between patients living inside Germany (DE) or outside Germany (non-DE). Between 2010 and 2020, 6,261,801 orthopedic procedures were coded for the DE group and 27,420 key procedures were identified for the non-DE group. Medical tourists were predominantly male and significantly younger than the domestic population. The linear regression analysis of the OPS codes over the past years showed a significantly different slope between the DE and non-DE groups only for the OPS code "hardware removal". With the COVID-19 pandemic, an overall decline in performed orthopedic procedures was observed for the non-DE and the DE group. A significant reduction below the 95\% prediction bands for the year 2020 could be shown for hardware removal and foot surgery (for DE), and for hardware removal, knee arthroplasty, foot surgery, and osteotomy (for non-DE). This study is the first to quantify inbound medical tourism in elective orthopedic surgery in Germany. The COVID-19 pandemic negatively affected many — but not all — areas of orthopedic surgery. It has to be seen how this negative trend will develop in the future.}, language = {en} } @article{HeinzEidmannAndersonetal.2023, author = {Heinz, Tizian and Eidmann, Annette and Anderson, Philip and Weißenberger, Manuel and Jakuscheit, Axel and Rudert, Maximilian and Stratos, Ioannis}, title = {Trends in computer-assisted surgery for total knee arthroplasty in Germany: an analysis based on the operative procedure classification system between 2010 to 2021}, series = {Journal of Clinical Medicine}, volume = {12}, journal = {Journal of Clinical Medicine}, number = {2}, issn = {2077-0383}, doi = {10.3390/jcm12020549}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304879}, year = {2023}, abstract = {Alignment strategies for primary total knee arthroplasty (TKA) have changed significantly over time with a shift towards a more individualized alignment goal. At the same time, computer-assisted surgery (CAS) has gained interest for intraoperative control and accuracy in implant positioning and limb alignment. Despite the often discussed benefits and drawbacks of robotics and navigation for TKA, the routine use of these new devices on a day-to-day basis remains obscure. Therefore, nationwide hospital billing data based on the Operation Procedure Classification System (OPS) were retrieved from the Federal Statistical Office of Germany for the period from 2010 to 2021. OPS codes for primary total knee arthroplasty (OPS code: 5-822*) were further analyzed regarding the usage of computer navigation (additional OPS code: 5-988) or robotic devices (additional OPS code: 5-987). Gender and age at the time of surgery were also assessed. The results show a total of 2,226,559 primary TKAs were implanted between 2010 and 2021, of which 2,044,914 were performed conventionally (91.84\% of all TKAs). A total of 170,276 TKAs were performed using navigation technique (7.65\% of all TKAs) and another 11,369 TKAs were performed using robotics (0.51\% of all TKAs). For the period from 2018 to 2021, a substantial increase in robot-assisted TKA (R-TKA) was observed, with an average increase rate of 84.74\% per year, while the number of navigated TKAs declined (-3.67\% per year). Computer-assisted surgery, and particularly robotics for TKA, are seeing growing popularity and stepwise translation into routine clinical use in Germany, with a steep increase rate of more than 80\% per year since 2018. Nevertheless, the majority of TKAs are still performed using manual instrumentation, rendering conventional TKA the currently unchanged gold standard.}, language = {en} } @phdthesis{Lindstroem2023, author = {Lindstr{\"o}m, Sarah Ingrid}, title = {Evaluation von Analysemethoden zur Validierung der Effektivit{\"a}t alltagstauglicher Trainingsmethoden bei {\"a}lteren M{\"a}nnern mit osteoporotischen Ver{\"a}nderungen}, doi = {10.25972/OPUS-34643}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-346431}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Aufgrund der immer {\"a}lterwerdenden Bev{\"o}lkerung kommt der Pr{\"a}vention von altersbedingten muskuloskelettalen Erkrankungen wie der Osteoporose und der Sarkopenie eine herausragende Bedeutung zu. Insbesondere f{\"u}r die Sarkopenie gibt es heute und auf absehbare Zeit keine kausale medikament{\"o}se Therapie. Somit stellt der Erhalt einer intakten Muskulatur durch k{\"o}rperliche Aktivit{\"a}t die zentrale S{\"a}ule f{\"u}r eine langfristig muskuloskelettale Gesundheit dar. Die aktuelle, wissenschaftliche Datenlage zeigt hierbei f{\"u}r progressives Krafttraining im Alter valide Ergebnisse. Durch die gezielte Beanspruchung der Muskulatur kann bis ins hohe Alter dem nat{\"u}rlichen Verlust der Muskelmasse und -qualit{\"a}t entgegengewirkt werden. Ein gezieltes Training der Wirbels{\"a}ule-umgebenden Muskulatur ist vor allem bei Menschen mit Osteoporose sinnvoll. Durch starke R{\"u}ckenmuskeln werden wichtige Alltagsbewegungen unterst{\"u}tzt und das Sturzrisiko kann reduziert werden. Ein klassisches progressives Krafttraining ist jedoch bei {\"a}lteren Menschen nicht immer durchf{\"u}hrbar, da diese oft an zus{\"a}tzlichen Erkrankungen leiden, welche ein intensives Krafttraining verbieten, oder allgemein zu schwach f{\"u}r eine solche Trainingsmodalit{\"a}t sind. Ziel dieser Studie war zus{\"a}tzlich zum Krafttraining alternative Trainingsmethoden zu testen, welche einfach und sicher im Alter integrierbar sind und keine sportlichen Vorkenntnisse der Teilnehmer erfordern. Im Fokus stand dabei die Kr{\"a}ftigung der Rumpfmuskulatur. Alternativ zum klassischen, progressivem Krafttraining (KT) wurden daher sogenannte Low-Impact-Methoden getestet, konkret handelte es sich dabei um Ganzk{\"o}rpervibrationstraining (WBV), das t{\"a}gliche Tragen einer federnden R{\"u}ckenorthese (OT) und Qi Gong (QG) als atmungs- und bewegungsorientiertes Konzept. Das Krafttraining zeigte dabei die gr{\"o}ßten Verbesserungen in der Rumpfkraft, dem prim{\"a}ren Endpunkt der Studie. Bei der Extensionskraft zeigte sich eine Zunahme von 28,0\%. (p=0,008) und bei der Flexionskraft von 17,2\% (p=0,008). Doch auch das WBV-Training und das Tragen der R{\"u}ckenorthese zeigten Verbesserungen der Rumpfkraft. Das QG-Training zeigte kaum Ver{\"a}nderungen der Rumpfkraft. Im Gruppenvergleich war die KT-Gruppe der QG-Gruppe in der Entwicklung der Extensionskraft signifikant {\"u}berlegen. Auch wenn die alternativen Trainingsmethoden keine signifikanten Ergebnisse im prim{\"a}ren Endpunkt dieser Studie zeigten, kam es zu signifikanten Verbesserungen in den sekund{\"a}ren Endpunkten. In der WBV-Gruppe kam es zu einem signifikanten Anstieg der Handkraft (p=0,023) und im CRT (p=0,007). In der OT-Gruppe war der CRT signifikant besser geworden (p=0,003). In der QG-Gruppe kam es zu tendenziellen Verbesserungen einiger Leistungsparameter, jedoch waren diese statistisch {\"u}berwiegend nicht signifikant. Ein wesentlicher Aspekt dieser Arbeit war jedoch, dass unabh{\"a}ngig von der jeweiligen Trainingsmodalit{\"a}t, vor allem die Teilnehmer, die ein erh{\"o}htes Risiko f{\"u}r muskul{\"a}re Defizite hatten, also Probanden ≥80 Jahre, Menschen mit pr{\"a}sarkopenem Muskelstatus, oder multimorbide Teilnehmer, am meisten von den Trainingsinterventionen profitierten. Hier fiel vor allem die signifikante Zunahme der Rumpfflexion in allen drei Subgruppen auf. Bei den Probanden ≥80 Jahren kam es in der Rumpfflexion zu einer Zunahme von 10,3\% (p=0,017), bei den pr{\"a}sarkopenen Probanden von 2,9\% (p=0,035) und bei den Multimorbiden von 16,3\% (p=0,001). Eine starke Rumpfvorderseite f{\"u}hrt zu einer aufrechten Haltung, erm{\"o}glicht Alltagsaktivit{\"a}ten wie Treppensteigen oder das Aufstehen von einem Stuhl und kann durch eine verbesserte Balance das Sturzrisiko vermindern. Bedeutsam ist auch, dass die Muskelmasse bei den pr{\"a}sarkopenen Probanden, unabh{\"a}ngig vom Training, signifikant gestiegen war und somit Sport auch bei einer reduzierten Muskelmasse sehr effektiv sein kann. Zudem verbesserte sich der CRT bei den pr{\"a}sarkopenen und multimorbiden Probanden signifikant, was umso erfreulicher ist, bedenkt man die Assoziation mit einer reduzierten F{\"a}higkeit von einem Stuhl aufzustehen und einer erh{\"o}hten Mortalit{\"a}t. Schlussendlich zeigen die Ergebnisse dieser Studie, dass Trainingsmodalit{\"a}ten, die gezielt die Rumpfmuskulatur adressieren, wie z.B. ein speziell zusammengestelltes Krafttraining, auch in h{\"o}herem Alter und bei Vorliegen eines erh{\"o}hten Frakturrisikos positive Effekte erzielen und zu signifikanten Verbesserungen der Rumpfkraft f{\"u}hren k{\"o}nnen. Allerdings zeigen auch weniger spezifische low-impact Trainingskonzepte durchaus positive Entwicklungen und stellen vor allem eine sichere Alternative mit nur geringem Anforderungsprofil dar. Besonders erfreulich scheint vor allem die Verbesserung der Parameter der Probanden mit einem erh{\"o}hten Risiko f{\"u}r muskul{\"a}re Defizite unabh{\"a}ngig von der zugelosten Trainingsintervention. Diese Ergebnisse stellen eine wertvolle Grundlage f{\"u}r zuk{\"u}nftige Forschungsvorhaben dar, welchen unter Ber{\"u}cksichtigung der globalen demographischen Entwicklungen sicherlich erhebliche Bedeutung zukommen wird.}, subject = {Osteoporose}, language = {de} } @phdthesis{Widmaier2023, author = {Widmaier, Louis}, title = {Die Regulation des Chemokinrezeptors CXCR4 durch Chemotherapeutika in Myelomzelllinien}, doi = {10.25972/OPUS-34568}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-345682}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Untersucht wurde der Einfluss mehrerer Chemotherapeutika auf den Chemokinrezeptor CXCR4 in Myelomzelllinien auf Ebene des Promotors, der mRNA und der Rezeptorverteilung, wobei drei Substanzen (Etoposid, Bortezomib und Dexamethason) als potenzielle Suppressoren des Promotors ausgemacht werden konnten. Abh{\"a}ngig vom Myelom-Zelltyp und der Dosierung k{\"o}nnen so evtl. R{\"u}ckschl{\"u}sse auf die beobachtete Suppression von CXCR4 bei erkrankten Patienten mit hoher CXCR4-Aktivit{\"a}t (hier: Malignes Myelom) durch die begleitende Chemotherapie gezogen werden, welche eine Diagnostik und Therapie bei diesen Patienten erschwert. Hintergrund: Hintergrund f{\"u}r diese Arbeit waren Beobachtungen in klinischen Fallstudien von Lapa et al. am Universit{\"a}tsklinikum W{\"u}rzburg, die sich auf CXCR4 bezogen, welches u.a. bei Patienten mit Multiplem Myelom {\"u}berexprimiert wird und dadurch bereits als Target f{\"u}r Diagnostik und Therapie in der Klinik Anwendung findet. Dabei konnte bei PET-CT Untersuchungen in der Nuklearmedizin beobachtet werden, dass es durch die begleitende Chemotherapie der Patienten zu einer Suppression des markierten CXCR4-Signals kam, so dass es nicht mehr zur Verlaufsbeobachtung und vor allem nicht mehr zur Radiotherapie und Therapiekontrolle verwendet werden konnte. Um den Einfluss und m{\"o}gliche Interaktionen der Chemotherapeutika auf CXCR4 zu untersuchen, war es Ziel dieser Arbeit, ein vergleichbares Szenario in-vitro nachzustellen und Einfl{\"u}sse messbar zu machen, um so m{\"o}gliche Ans{\"a}tze und Verbesserungsvorschl{\"a}ge f{\"u}r die klinische Anwendung zu liefern. Methoden/Ergebnisse: Hierf{\"u}r wurden im ersten Teil INA-6 (Myelomzellen) und Mesenchymale Stammzellen (MSC) kultiviert, in Ko-Kultur gebracht und nach einer bestimmten Zeit wieder getrennt, um anschließend den gegenseitigen Einfluss in Bezug auf CXCR4 zu messen. Zudem wurde der Einfluss von Dexamethason untersucht. Es zeigte sich eine enge Bindung zwischen INA-6 und MSC sowie eine hohe CXCR4-Aktivit{\"a}t bei INA-6, jedoch konnte keine Induktion der CXCR4-Aktivit{\"a}t in MSC durch INA-6-Kontakt oder Dexamethason quantifiziert werden. Die Immunzytologie erwies sich aufgrund einer schweren Anf{\"a}rbbarkeit von CXCR4 - auch mit verschiedensten Antik{\"o}rpern und sogar Liganden-gekoppeltem Farbstoff- als kaum auswertbar, wobei eine Darstellung von CXCR4 generell aber gelang. Der CXCR4-Promotor wurde mittels Software genauer analysiert, wobei einige relevante Bindestellen, u.a. f{\"u}r Glukokortikoide und NFkB gefunden wurden. Die Herstellung eines CXCR4- pGl4.14-Promotor-Konstrukts war erfolgreich, ebenso dessen Einschleusung in Myelomzellen. Auch gelang die Herstellung stabiler transfizierter INA-6, sodass mit diesen anschließend konstantere Ergebnisse erzielt werden konnten. Im gr{\"o}ßten Teil der Arbeit wurden geeignete Chemotherapeutika-Konzentrationen ermittelt und in Viabilit{\"a}ts- und Apoptose-Versuchen {\"u}berpr{\"u}ft. Die Stimulationsversuche mit diesen zeigten variable Effekte abh{\"a}ngig vom Zelltyp (INA-6, MM1S), jedoch konnten Bortezomib, Etoposid und Dexamethason konzentrationsabh{\"a}ngig als starke Suppressoren der CXCR4-Aktivit{\"a}t ausgemacht werden, was sich v.a. auf Ebene der Promotoraktivit{\"a}t - gemessen mittels Luciferase - zeigte. Interpretation: In-vitro konnten somit drei potenzielle Suppressoren der CXCR4-Aktivit{\"a}t ausgemacht werden: Etoposid, Bortezomib und Dexamethason. Zumindest beim INA-6-Zelltyp fiel dieser Effekt deutlich aus, wobei in der Klinik der entsprechende Zelltyp sowie die Dosierung der Medikamente ber{\"u}cksichtigt werden m{\"u}ssen. Hinzu kommen weitere Einflussfaktoren des menschlichen K{\"o}rpers, die nicht ber{\"u}cksichtig werden konnten. Die genauen Mechanismen der Suppression k{\"o}nnten sich aus den Bindestellen des Promotors erkl{\"a}ren, die von uns analysiert wurden, aber auf die in weiteren Arbeiten noch n{\"a}her eingegangen werden muss.}, subject = {Bortezomib}, language = {de} } @phdthesis{DeGraafverhWeinke2023, author = {De Graaf [verh. Weinke], Karlijn}, title = {Analyse des postoperativen Offsets nach H{\"u}ftprothesenwechsel}, doi = {10.25972/OPUS-32910}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-329104}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Die Rekonstruktion der Anatomie einer nativen H{\"u}fte sowie deren nat{\"u}rlichen Biomechanik ist eine essenzielle Voraussetzung f{\"u}r eine zufriedenstellende Funktion einer H{\"u}ftprothese. Diese Studie besch{\"a}ftigte sich mit dem Zusammenhang der Ver{\"a}nderung des Femoralen Offsets (FO) und dem klinischen Outcome der Patienten nach H{\"u}ftprothesenwechsel. 88 Patienten, welche sich einem H{\"u}ftprothesenwechsel unterzogen, wurden untersucht. Es wurden in pr{\"a}- und postoperativen Becken{\"u}bersichtsaufnahmen das Femorale Offset, sowie weitere statische Parameter gemessen und verglichen. Die Ergebnisse wurden mit dem klinischen Outcome korreliert. Dies erfolgte anhand des Harris Hip Score (HHS), der Visuellen Analogskala (VAS) und des Merle d'Aubigne und Postel Score (MdAS). Bez{\"u}glich der Rekonstruktion des FO kam es zu einem zufriedenstellenden Ergebnis. In 22,6\% konnte ein gleichgroßes, in 54\% ein vergr{\"o}ßertes und in 22\% ein verkleiner- tes FO gemessen werden. Das klinische Outcome ergab durchschnittlich ein gutes bis sehr gutes klnisches Ergebnis in allen erhobenen Scores (Gesamtpunktzahl: HHS 75,09; MdAS 14,36; VAS 0,71). Ein signifikant besseres Ergebnis hinsichtlich der Beweglichkeit und Funktionalit{\"a}t wurde bei gleichbleibendem und vergr{\"o}ßertem FO in allen klinischen Tests (VAS, HHS, MdAS) erzielt. Bei verkleinertem FO traten jedoch weniger Schmerzen auf. Die Rekonstruktion des FO ist nachweislich von Bedeutung f{\"u}r das klinische Outcome nach H{\"u}ftprothesenwechsel. Sie beeinflusst den Hebelarm der Muskulatur, was bei einem vergr{\"o}ßertem FO zu einer verbesserten Beweglichkeit und Funktionalit{\"a}t des Gelenkes f{\"u}hrt, jedoch auch aufgrund der Dehnung des Bandapparats und der Muskulatur eine vermehrte Schmerzsymptomatik verursachen kann. Die Ergebnisse dieser Arbeit decken sich mit {\"a}hnlichen Studien, welche das FO bei prim{\"a}rer H-TEP- Implantation untersuchten.}, language = {de} } @article{SeilerEbertRudertetal.2022, author = {Seiler, Jonas and Ebert, Regina and Rudert, Maximilian and Herrmann, Marietta and Leich, Ellen and Weißenberger, Manuela and Horas, Konstantin}, title = {Bone metastases of diverse primary origin frequently express the VDR (vitamin D receptor) and CYP24A1}, series = {Journal of Clinical Medicine}, volume = {11}, journal = {Journal of Clinical Medicine}, number = {21}, issn = {2077-0383}, doi = {10.3390/jcm11216537}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297377}, year = {2022}, abstract = {Active vitamin D (1,25(OH)2D3) is known to exert direct anti-cancer actions on various malignant tissues through binding to the vitamin D receptor (VDR). These effects have been demonstrated in breast, prostate, renal and thyroid cancers, which all have a high propensity to metastasise to bone. In addition, there is evidence that vitamin D catabolism via 24-hydroxylase (CYP24A1) is altered in tumour cells, thus, reducing local active vitamin D levels in cancer cells. The aim of this study was to assess VDR and CYP24A1 expression in various types of bone metastases by using immunohistochemistry. Overall, a high total VDR protein expression was detected in 59\% of cases (39/66). There was a non-significant trend of high-grade tumours towards the low nuclear VDR expression (p = 0.07). Notably, patients with further distant metastases had a reduced nuclear VDR expression (p = 0.03). Furthermore, a high CYP24A1 expression was detected in 59\% (39/66) of bone metastases. There was a significant positive correlation between nuclear VDR and CYP24A1 expression (p = 0.001). Collectively, the VDR and CYP24A1 were widely expressed in a multitude of bone metastases, pointing to a potential role of vitamin D signalling in cancer progression. This is of high clinical relevance, as vitamin D deficiency is frequent in patients with bone metastases.}, language = {en} } @article{RakNedopilSayreetal.2022, author = {Rak, Dominik and Nedopil, Alexander J. and Sayre, Eric C. and Masri, Bassam A. and Rudert, Maximilian}, title = {Postoperative inpatient rehabilitation does not increase knee function after primary total knee arthroplasty}, series = {Journal of Personalized Medicine}, volume = {12}, journal = {Journal of Personalized Medicine}, number = {11}, issn = {2075-4426}, doi = {10.3390/jpm12111934}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297322}, year = {2022}, abstract = {Inpatient rehabilitation (IR) is a common postoperative protocol after total knee replacement (TKA). Because IR is expensive and should therefore be justified, this study determined the difference in knee function one year after TKA in patients treated with IR or outpatient rehabilitation, fast-track rehabilitation (FTR) in particular, which also entails a reduced hospital length of stay. A total of 205 patients were included in this multi-center prospective cohort study. Of the patients, 104 had primary TKA at a German university hospital and received IR, while 101 had primary TKA at a Canadian university hospital and received FTR. Patients receiving IR or FTR were matched by pre-operative demographics and knee function. Oxford Knee Score (OKS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), and EuroQol visual analogue scale (EQ-VAS) determined knee function one year after surgery. Patients receiving IR had a 2.8-point lower improvement in OKS (p = 0.001), a 6.7-point lower improvement in WOMAC (p = 0.063), and a 12.3-point higher improvement in EQ-VAS (p = 0.281) than patients receiving FTR. IR does not provide long-term benefits to patient recovery after primary uncomplicated TKA under the current rehabilitation regime.}, language = {en} } @article{SappeyMarinierHowellNedopiletal.2022, author = {Sappey-Marinier, Elliot and Howell, Stephen M. and Nedopil, Alexander J. and Hull, Maury L.}, title = {The trochlear groove of a femoral component designed for kinematic alignment is lateral to the quadriceps line of force and better laterally covers the anterior femoral resection than a mechanical alignment design}, series = {Journal of Personalized Medicine}, volume = {12}, journal = {Journal of Personalized Medicine}, number = {10}, issn = {2075-4426}, doi = {10.3390/jpm12101724}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290482}, year = {2022}, abstract = {Background: A concern about kinematically aligned (KA) total knee arthroplasty (TKA) is that it relies on femoral components designed for mechanical alignment (MAd-FC) that could affect patellar tracking, in part, because of a trochlear groove orientation that is typically 6° from vertical. KA sets the femoral component coincident to the patient's pre-arthritic distal and posterior femoral joint lines and restores the Q-angle, which varies widely. Relative to KA and the native knee, aligning the femoral component with MA changes most distal joint lines and Q-angles, and rotates the posterior joint line externally laterally covering the anterior femoral resection. Whether switching from a MAd- to a KAd-FC with a wider trochlear groove orientation of 20.5° from vertical results in radiographic measures known to promote patellar tracking is unknown. The primary aim was to determine whether a KAd-FC sets the trochlear groove lateral to the quadriceps line of force (QLF), better laterally covers the anterior femoral resection, and reduces lateral patella tilt relative to a MAd-FC. The secondary objective was to determine at six weeks whether the KAd-FC resulted in a higher complication rate, less knee extension and flexion, and lower clinical outcomes. Methods: Between April 2019 and July 2022, two surgeons performed sequential bilateral unrestricted caliper-verified KA TKA with manual instruments on thirty-six patients with a KAd- and MAd-FC in opposite knees. An observer measured the angle between a line best-fit to the deepest valley of the trochlea and a line representing the QLF that indicated the patient's Q-angle. When the trochlear groove was lateral or medial relative to the QLF, the angle is denoted + or -, and the femoral component included or excluded the patient's Q-angle, respectively. Software measured the lateral undercoverage of the anterior femoral resection on a Computed Tomography (CT) scan, and the patella tilt angle (PTA) on a skyline radiograph. Complications, knee extension and flexion measurements, Oxford Knee Score, KOOS Jr, and Forgotten Joint Score were recorded pre- and post-operatively (at 6 weeks). A paired Student's T-test determined the difference between the KA TKAs with a KAd-FC and MAd-FC with a significance set at p < 0.05. Results: The final analysis included thirty-five patients. The 20.5° trochlear groove of the KAd-FC was lateral to the QLF in 100\% (15 ± 3°) of TKAs, which was greater than the 69\% (1 ± 3°) lateral to the QLF with the 6° trochlear groove of the MAd-FC (p < 0.001). The KAd-FC's 2 ± 1.9 mm lateral undercoverage of the anterior femoral resection was less than the 4.4 ± 1.5 mm for the MAd-FC (p < 0.001). The PTA, complication rate, knee extension and flexion, and clinical outcome measures did not differ between component designs. Conclusions: The KA TKA with a KAd-FC resulted in a trochlear groove lateral to the QLF that included the Q-angle in all patients, and negligible lateral undercoverage of the anterior femoral resection. These newly described radiographic parameters could be helpful when investigating femoral components designed for KA with the intent of promoting patellofemoral kinematics.}, language = {en} } @phdthesis{Ege2023, author = {Ege, Carolin}, title = {Einfluss der Phosphodiesterase 10A auf cAMP-abh{\"a}ngige Signalwege und deren Effekt auf osteogene Differenzierung und Mechanotransduktion von mesenchymalen Stromazellen}, doi = {10.25972/OPUS-32832}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-328327}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Humane mesenchymale Stromazellen sind in der Lage in osteogene Zellen zu differenzieren, und f{\"u}r diese osteogene Differenzierung ist mechanische Belastung ein relevanter Kostimulus. Mechanotransduktion hat zur Folge, dass second messenger wie cAMP und cGMP gebildet werden und sich die Ca2+-Konzentration erh{\"o}ht, welche wiederum Transkriptionsfaktoren aktivieren, die die Regulation von Genen osteogener Marker vermitteln. Die second messenger cAMP und cGMP werden abgebaut durch Phosphodiesterasen, jedoch ist die Rolle dieser Phosphodiesterasen w{\"a}hrend der osteogenen Differenzierung oder Mechanotransduktion weiterhin unklar. Das Ziel dieser Arbeit war es, herauszufinden, inwieweit im Besonderen die Phosphodiesterase 10A einen Einfluss nimmt auf die osteogene Differenzierung und die Mechanotransduktion von mesenchymalen Stromazellen und inwiefern sie dabei die cAMP-abh{\"a}ngigen Signalwege moduliert. Langfristig soll hiermit herausgefunden wer-den, welche Bedeutung die PDE10A auf altersinduzierte Krankheiten hat, wobei der Fokus zun{\"a}chst auf der Osteoporose liegen soll. Um dies zu erreichen, wurden experimentelle Versuche zun{\"a}chst mit HEK293- und hMSC-TERT-Zellen als Modell f{\"u}r mesenchymale Stromazellen durchgef{\"u}hrt, dann auch mit den mesenchymalen Stromazellen selbst. Untersucht wurde der Einfluss des PDE10A-Inhibitors Papaverin auf die Zellen und auf deren mechanische Induzierbarkeit, sowieso auf die osteogene Differenzierung der hMSC. Außerdem wurden weitere mechanische Versuche durchgef{\"u}hrt, zur {\"U}berpr{\"u}fung des Effekts der Phosphodiesterase 10A. Es wurde beobachtet, dass die Inhibierung von PDE10A mit Papaverin die osteogene Differenzierung und Mineralisierung vermindert. Außerdem gab es einen ersten Hinweis, dass eine {\"U}berexpression von PDE10A schw{\"a}chenden Einfluss nimmt auf die Expression mechanoresponsiver Gene. Nachfolgend auf diese Arbeit wurde erkannt, dass die Expression von mechanoresponsiven Genen durch die PDE10A-Inhibition unterdr{\"u}ckt wird.}, subject = {Mesenchymzelle}, language = {de} } @phdthesis{Loeffler2023, author = {L{\"o}ffler, Miriam}, title = {Bestimmung der optimalen Positionierung eines Kirschner-Drahtes zur tempor{\"a}ren Transfixation des AC-Gelenks bei der operativen Behandlung der AC-Sprengung}, doi = {10.25972/OPUS-32874}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-328742}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Die AC-Sprengung ist eine weit verbreitete Verletzung des Schulterg{\"u}rtels und am h{\"a}ufigsten auf einen Sportunfall vorwiegend junger M{\"a}nner zur{\"u}ckzuf{\"u}hren. Die optimale Therapie wird kontrovers diskutiert, keine der rund 150 OP-Methoden hat sich bisher als den anderen {\"u}berlegen erwiesen. Allerdings gelten Operationen, bei denen das AC-Gelenk tempor{\"a}r durch eine intramedull{\"a}re Schienung per Kirschner-Draht ruhiggestellt wird, als sehr zuverl{\"a}ssig. Sie sind aufgrund einer sehr variablen Anatomie jedoch auch f{\"u}r erfahrene Operateure technisch anspruchsvoll. Ziel dieser Arbeit ist es daher, mithilfe der gewonnenen Kenntnisse zur idealen Lage eines K-Drahtes das operative Vorgehen zur tempor{\"a}ren Transfixation des ACGs k{\"u}nftig durch eine gezieltere Platzierung zu erleichtern, somit die Operationsmethode zu optimieren und folglich das Outcome zu verbessern. F{\"u}r diese Arbeit wurden bereits vorliegende anonymisierte computertomographische Daten gesunder AC-Gelenke nach ihrer physiologischen Anatomie sowie der Lage eines virtuell ideal platzierten transartikul{\"a}ren K-Drahtes ausgewertet. Hierf{\"u}r wurden CT-Daten von insgesamt 66 Schultern herangezogen, der Epidemiologie der AC-Sprengung entsprechend waren hiervon 59 Patienten und 7 Patientinnen zuzuordnen. Die erhobenen Daten zeigen, dass die Lage des Eintrittspunktes idealerweise durch den orthogonalen Abstand des Drahtes zur Acromionspitze definiert wird und durchschnittlich 12,89 mm betr{\"a}gt. Er ist prim{\"a}r abh{\"a}ngig von der K{\"o}rpergr{\"o}ße und kann daher pr{\"a}operativ anhand einer Regressionsgeraden individuell f{\"u}r jeden Patienten bestimmt werden. Der Drahtverlauf sollte prim{\"a}r durch Zielen auf den markierten Austrittspunkt definiert werden. Das Absch{\"a}tzen der Bohrrichtung anhand von Winkeln erscheint nahezu unm{\"o}glich. Die Drahtl{\"a}nge bel{\"a}uft sich im Mittel auf 58,06 mm. Je kleiner der AC-Winkel ist, desto steiler und auch k{\"u}rzer zeigt sich der Drahtverlauf. Die Lage des Austrittspunktes korreliert ebenfalls signifikant mit dem AC-Winkel und kann daher nach erfolgter Winkelmessung im R{\"o}ntgenbild anhand einer Regressionsgeraden abgelesen werden. Der mithilfe der Daten ermittelte Austrittspunkt eines ideal platzierten K-Drahtes befindet sich durchschnittlich auf H{\"o}he des lateralen Claviculawinkels und somit auf H{\"o}he der CC-B{\"a}nder. Bei der nur geringen Fallzahl weiblicher Patienten besteht eine noch eingeschr{\"a}nkte Aussagekraft bez{\"u}glich geschlechtsabh{\"a}ngiger Lageunterschiede. Nach bisher vorliegenden Daten kann eine geschlechtsunabh{\"a}ngige OP-Planung erfolgen. Relevante ACG-Typ abh{\"a}ngige Lageunterschiede konnten ebenfalls nicht festgestellt werden, eine pr{\"a}operative Bestimmung des anatomischen ACG-Typs ist daher nicht erforderlich. Die erhobenen Daten deuten darauf hin, dass die ideale Drahtplatzierung unter Einhaltung aller Drahtlagekriterien nicht immer m{\"o}glich ist. Betroffen sind kleine Patienten (Grenzwert: 158,6 cm K{\"o}rpergr{\"o}ße), bei denen der Mindestabstand zur Acromionspitze nicht sichergestellt werden kann. Zudem besteht bei Patienten mit einem kleinen AC-Winkel (Grenzwert: 156,2°) das Risiko, die Mindestdrahtl{\"a}nge innerhalb der Clavicula zu unterschreiten. In diesen F{\"a}llen muss entweder dezent von der idealen Drahtlage abgewichen oder auf ein alternatives OP-Verfahren ausgewichen werden.}, subject = {Akromioklavikulargelenk}, language = {de} } @phdthesis{Altmann2023, author = {Altmann, Stephan}, title = {Characterization of Metabolic Glycoengineering in Mesenchymal Stromal Cells for its Application in thermoresponsive Bioinks}, doi = {10.25972/OPUS-29100}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-291003}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {This work developed during the first funding period of the subproject B05 in the framework of the interdisciplinary research consortium TRR 225 'From the Fundamentals of Biofabrication toward functional Tissue Models' and was part of a cooperation between the Orthopedic Department represented by Prof. Dr. Regina Ebert and the Institute of Organic Chemistry represented by Prof. Dr. J{\"u}rgen Seibel. This project dealed with cellular behavior during the bioprinting process and how to influence it by modifying the cell glycocalyx with functional target molecules. The focus was on the impact of potential shear stress, that cells experience when they get processed in thermoresponsive bioinks, and a way to increase the cell stiffness via metabolic glycoengineering to attenuate shear forces. For the characterization of the metabolic glycoengineering, four different peracetylated and four non-acetylated modified monosaccharides (two mannose and two sialic acid sugars) were tested in primary human mesenchymal stromal cells (hMSC) and telomerase-immortalized hMSC (hMSC-TERT). Viability results demonstrated a dose-dependent correlation for all sugars, at which hMSC-TERT seemed to be more susceptible leading to lower viability rates. The assessment of the incorporation efficiencies was performed by click chemistry using fluorescent dyes and revealed also a dose-dependent correlation for all mannose and sialic acid sugars, while glucose and galactose variants were not detected in the glycocalyx. However, incorporation efficiencies were highest when using mannose sugars in the primary hMSC. A subsequent analysis of the temporal retention of the incorporated monosaccharides showed a constant declining fluorescence signal up to 6 d for azido mannose in hMSC-TERT, whereas no signal could be detected for alkyne mannose after 2 d. Investigation of the differentiation potential and expression of different target genes revealed no impairment after incubation with mannose sugars, indicating a normal phenotype for hMSC-TERT. Following the successful establishment of the method, either a coumarin derivative or an artificial galectin 1 ligand were incorporated into the cell glycocalyx of hMSC-TERT as functional target molecule. The biophysical analysis via shear flow deformation cytometry revealed a slightly increased cell stiffness and lowered fluidity for both molecules. A further part of this project aimed to control lectin-mediated cell adhesion by artificial galectin 1 ligands. As that hypothesis was settled in the work group of Prof. Dr. J{\"u}rgen Seibel, this work supported with an initial characterization of galectin 1 as part of the hMSC biology. A stable galectin 1 expression at gene and protein level in both hMSC and hMSC-TERT could be confirmed, at which immunocytochemical stainings could detect the protein only in the glycocalyx. The treatment of hMSC-TERT with a galectin 1 ligand in different concentrations did not show an altered gene expression of galectin 1. However, these first data in addition to the investigation of stiffness confirmed the applicability of specific and artificial IV galectin 1 ligands in biofabrication approaches to alter cell properties of hMSC. To conclude, metabolic glycoengineering has been successfully implemented in hMSC and hMSC-TERT to introduce glycocalyx modifications which reside there for several days. A proof of concept was carried out by the increase of cell stiffness and fluidity by the incorporation of a coumarin derivative or an artificial galectin 1 ligand. For the characterization of shear stress impact on cells after printing in thermoresponsive bioinks, the processing of hMSC-TERT (mixing or additionally printing) with Pluronic F127 or Polyoxazoline-Polyoxazine (POx-POzi) polymer solution was investigated. While there were no changes in viability when using POx-POzi bioink, processing with Pluronic F127 indicated slightly lower viability and increased apoptosis activity. Assessment of cellular responses to potential shear stress showed no reorganization of the cytoskeleton independent of the bioink, but highly increased expression of the mechanoresponsive proto-oncogene c Fos which was more pronounced when using Pluronic F127 and just mixed with the bioinks. Interestingly, processing of the mechanoresponsive reporter cell line hMSC-TERT-AP1 revealed slightly elevated mechanotransduction activity when using POx-POzi polymer and just mixed with the bioinks as well. In conclusion, hMSC-TERT embedded in thermoresponsive bioinks might shortly experience shear stress during the printing process, but that did not lead to remarkable cell damage likely due to the rheological properties of the bioinks. Furthermore, the printing experiments also suggested that cells do not sense more shear stress when additionally printed.}, subject = {Glykobiologie}, language = {en} } @article{StratosRinasSchroepferetal.2023, author = {Stratos, Ioannis and Rinas, Ingmar and Schr{\"o}pfer, Konrad and Hink, Katharina and Herlyn, Philipp and B{\"a}umler, Mario and Histing, Tina and Bruhn, Sven and M{\"u}ller-Hilke, Brigitte and Menger, Michael D. and Vollmar, Brigitte and Mittlmeier, Thomas}, title = {Effects on bone and muscle upon treadmill interval training in hypogonadal male rats}, series = {Biomedicines}, volume = {11}, journal = {Biomedicines}, number = {5}, issn = {2227-9059}, doi = {10.3390/biomedicines11051370}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319266}, year = {2023}, abstract = {Testosterone deficiency in males is linked to various pathological conditions, including muscle and bone loss. This study evaluated the potential of different training modalities to counteract these losses in hypogonadal male rats. A total of 54 male Wistar rats underwent either castration (ORX, n = 18) or sham castration (n = 18), with 18 castrated rats engaging in uphill, level, or downhill interval treadmill training. Analyses were conducted at 4, 8, and 12 weeks postsurgery. Muscle force of the soleus muscle, muscle tissue samples, and bone characteristics were analyzed. No significant differences were observed in cortical bone characteristics. Castrated rats experienced decreased trabecular bone mineral density compared to sham-operated rats. However, 12 weeks of training increased trabecular bone mineral density, with no significant differences among groups. Muscle force measurements revealed decreased tetanic force in castrated rats at week 12, while uphill and downhill interval training restored force to sham group levels and led to muscle hypertrophy compared to ORX animals. Linear regression analyses showed a positive correlation between bone biomechanical characteristics and muscle force. The findings suggest that running exercise can prevent bone loss in osteoporosis, with similar bone restoration effects observed across different training modalities.}, language = {en} } @article{KronerWeiglChuRudertetal.2023, author = {Kroner-Weigl, Niklas and Chu, Jin and Rudert, Maximilian and Alt, Volker and Shukunami, Chisa and Docheva, Denitsa}, title = {Dexamethasone is not sufficient to facilitate tenogenic differentiation of dermal fibroblasts in a 3D organoid model}, series = {Biomedicines}, volume = {11}, journal = {Biomedicines}, number = {3}, issn = {2227-9059}, doi = {10.3390/biomedicines11030772}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311234}, year = {2023}, abstract = {Self-assembling three-dimensional organoids that do not rely on an exogenous scaffold but maintain their native cell-to-cell and cell-to-matrix interactions represent a promising model in the field of tendon tissue engineering. We have identified dermal fibroblasts (DFs) as a potential cell type for generating functional tendon-like tissue. The glucocorticoid dexamethasone (DEX) has been shown to regulate cell proliferation and facilitate differentiation towards other mesenchymal lineages. Therefore, we hypothesized that the administration of DEX could reduce excessive DF proliferation and thus, facilitate the tenogenic differentiation of DFs using a previously established 3D organoid model combined with dose-dependent application of DEX. Interestingly, the results demonstrated that DEX, in all tested concentrations, was not sufficient to notably induce the tenogenic differentiation of human DFs and DEX-treated organoids did not have clear advantages over untreated control organoids. Moreover, high concentrations of DEX exerted a negative impact on the organoid phenotype. Nevertheless, the expression profile of tendon-related genes of untreated and 10 nM DEX-treated DF organoids was largely comparable to organoids formed by tendon-derived cells, which is encouraging for further investigations on utilizing DFs for tendon tissue engineering.}, language = {en} } @phdthesis{George2023, author = {George, Enrico}, title = {Tempor{\"a}re Hemiepiphyseodese bei idiopathischen Beinachsenfehlstellungen - klinische und radiologische Gegen{\"u}berstellung der VaWiKo® EPI-PLATTE und PediatrOS™ FlexTack™ - eine retrospektive Studie}, doi = {10.25972/OPUS-32733}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-327338}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Beinachsenfehlstellungen im Kindesalter z{\"a}hlen zu den h{\"a}ufigsten Wachstums- und Entwicklungsst{\"o}rungen der unteren Extremit{\"a}ten. Eine daraus resultierende Pr{\"a}disposition f{\"u}r degenerative Erkrankungen begr{\"u}ndet die Bedeutung der operativen Korrektur bei noch ge{\"o}ffneten Wachstumsfugen mittels tempor{\"a}rer Hemiepiphyseodese. Zur Beurteilung des Therapieerfolges wurden insgesamt 140 Beinachsen mit idiopathischen Achsfehlstellungen retrospektiv betrachtet. In den Jahren 2017 bis 2021 wurden mit der VaWiKo® EPI-PLATTE und der PediatrOS™ FlexTack™ zwei unterschiedliche Implantate zur tempor{\"a}ren Hemiepiphyseodese in der kinderorthop{\"a}dischen Klinik des Marienstift Arnstadt verwendet. Entsprechend der verwendeten Implantate erfolgte die Einteilung in zwei Patientengruppen, die sowohl klinisch als auch radiologisch jeweils pr{\"a}- und postoperativ gegen{\"u}bergestellt wurden. Bei Patienten/-innen mit einer Beinachsenkorrektur durch die VaWiKo® EPI-PLATTE ergab sich durchschnittlich eine signifikant k{\"u}rzere Explantationsdauer (EP 26,05 min; FT 35,60 min) sowie eine k{\"u}rzere Durchleuchtungszeit in Winkelminuten (EP 0,03; FT 0,07) im Rahmen der Explantation. Dem gegen{\"u}ber steht die signifikant k{\"u}rzere station{\"a}re Aufenthaltsdauer in Tagen bei der Im- und Explantation der PediatrOS™ FlexTack™. (EP 5,43/ 3,73; FT 4,52/ 3,35). In Bezug auf die zur Wachstumskorrektur ben{\"o}tigten Zeit in Tagen resultiert in der Varus-Gruppe ein signifikanter Unterschied zugunsten der PediatrOS™ FlexTack™, (EP 517; FT 299) wohingegen sich in der Valgus-Gruppe kein signifikanter Unterschied zwischen beiden Implantaten zeigte (EP 343; FT 334). Zusammenfassend traten zwei Komplikationen auf, die jeweils Kinder aus der PediatrOS™ FlexTack™-Gruppe betrafen. Sowohl die PediatrOS™ FlexTack™ als auch die VaWiKo® EPI-PLATTE konnten die gew{\"u}nschte Beinachsenkorrektur erzielen. Die in der Literatur mit der PediatrOS™ FlexTack™ in Verbindung gebrachten k{\"u}rzeren Implantations- und Durchleuchtungszeiten sowie die k{\"u}rzeren Therapiedauern des Genu valgum konnten im Vergleich zur VaWiKo® EPI-PLATTE nicht best{\"a}tigt werden.}, subject = {Epiphyseodese}, language = {de} } @phdthesis{Reck2023, author = {Reck, Alexander Reiner}, title = {Die operative Korrektur der Madelung'schen Deformit{\"a}t}, doi = {10.25972/OPUS-32660}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-326604}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Im Rahmen dieser retrospektiven Studie zur Madelung-Deformit{\"a}t wurden 23 H{\"a}nde von 16 Patienten, welche in einem Zeitraum von 17,5 Jahren mit einer Radiuskorrekturosteotomie (RKO) oder eine Physiolyse mit Vickers-Band-Entfernung (PHY) behandelt wurden, nachuntersucht und bez{\"u}glich des OP-Outcomes verglichen. Die Gruppe RKO umfasste 14 H{\"a}nde mit einem Durchschnittsalter von 22 Jahren und einer durchschnittlichen Follow-Up-Zeitraum von 7 Jahren. Die Gruppe PHY bestand aus 9 H{\"a}nden mit einem Durchschnittsalter von 13 Jahren und einem mittleren Follow-Up-Zeitraum von 5 Jahren. In unserem Kollektiv konnte die Radiuskorrektur eine Verbesserung bez{\"u}glich der Schmerzen, des subjektiven Gesundheitsstatus, der Beweglichkeit und der radiologischen Auspr{\"a}gung der Deformit{\"a}t herbeif{\"u}hren. Die vorliegenden Ergebnisse st{\"u}tzen damit die aus der bisherigen Literatur ableitbare Vermutung, dass dieses Verfahren zur Therapie der Madelung-Deformit{\"a}t geeignet ist. Die Physiolyse mit Vickers-Band-Entfernung konnte die Progredienz der Erkrankung in unserer Stichprobe nicht suffizient aufhalten, wie es anhand der bisherigen Literatur allerdings zu erwarten gewesen w{\"a}re. Infolgedessen kam es in der Gruppe PHY zu einer Zunahme der Schmerzen und der Auspr{\"a}gung der Deformit{\"a}t sowie einer Verschlechterung des Gesundheitsstatus. Der Grund hierf{\"u}r lag wahrscheinlich im, verglichen mit der bisherigen Literatur, relativ hohen Durchschnittsalter der Gruppe. Es l{\"a}sst sich schlussfolgern, dass die Physiolyse mit Vickers-Band-Entfernung ihre Wirkung vor allem im Kindesalter voll entfaltet. Im Einklang mit der bisherigen Literatur konnte keine Korrelation zwischen den aktuellen radiologischen und klinischen Befunden beobachtet werden. Jedoch zeigte sich ein augenscheinlicher Zusammenhang zwischen der Ver{\"a}nderung der radiologischen Parameter und der Ver{\"a}nderung des klinischen Befindens, was einen Nutzen der McCarroll-Parameter im Rahmen der OP-Planung nahelegt.}, subject = {Handdeformit{\"a}t}, language = {de} } @article{DhaliwalZamoraNedopiletal.2022, author = {Dhaliwal, Anand and Zamora, Tomas and Nedopil, Alexander J. and Howell, Stephen M. and Hull, Maury L.}, title = {Six commonly used postoperative radiographic alignment parameters do not predict clinical outcome scores after unrestricted caliper-verified kinematically aligned TKA}, series = {Journal of Personalized Medicine}, volume = {12}, journal = {Journal of Personalized Medicine}, number = {9}, issn = {2075-4426}, doi = {10.3390/jpm12091468}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288186}, year = {2022}, abstract = {Background: Unrestricted caliper-verified kinematically aligned (KA) TKA restores patient's prearthritic coronal and sagittal alignments, which have a wide range containing outliers that concern the surgeon practicing mechanical alignment (MA). Therefore, knowing which radiographic parameters are associated with dissatisfaction could help a surgeon decide whether to rely on them as criteria for revising an unhappy patient with a primary KA TKA using MA principles. Hence, we determined whether the femoral mechanical angle (FMA), hip-knee-ankle angle (HKAA), tibial mechanical angle (TMA), tibial slope angle (TSA), and the indicators of patellofemoral tracking, including patella tilt angle (PTA) and the lateral undercoverage of the trochlear resection (LUCTR), are associated with clinical outcome scores. Methods: Forty-three patients with a CT scan and skyline radiograph after a KA TKA with PCL retention and medial stabilized design were analyzed. Linear regression determined the strength of the association between the FMA, HKA angle, PTS, PTA, and LUCTR and the forgotten joint score (FJS), Oxford knee score (OKS), and KOOS Jr score obtained at a mean of 23 months. Results: There was no correlation between the FMA (range 2° varus to -10° valgus), HKAA (range 10° varus to -9° valgus), TMA (range 10° varus to -0° valgus), TSA (range 14° posterior to -4° anterior), PTA (range, -10° medial to 14° lateral), and the LUCTR resection (range 2 to 9 mm) and the FJS (median 83), the OKS (median 44), and the KOOS Jr (median 85) (r = 0.000 to 0.079). Conclusions: Surgeons should be cautious about using postoperative FMA, HKAA, TMA, TSA, PTA, and LUCTR values within the present study's reported ranges to explain success and dissatisfaction after KA TKA.}, language = {en} } @article{NedopilHowellHull2022, author = {Nedopil, Alexander J. and Howell, Stephen M. and Hull, Maury L.}, title = {Measurement of tibial orientation helps select the optimal insert thickness to personalize PCL tension in a medial ball-in-socket TKA}, series = {Journal of Personalized Medicine}, volume = {12}, journal = {Journal of Personalized Medicine}, number = {9}, issn = {2075-4426}, doi = {10.3390/jpm12091427}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-286232}, year = {2022}, abstract = {As the conformity of a medial ball-in-socket total knee arthroplasty (TKA) provides intrinsic anterior-posterior (A-P) stability, surgeons cannot rely on the manual examination of sagittal laxity to identify the optimal insert thickness. Instead, the present study determined whether measuring tibial axial orientation in extension and 90° flexion with an insert goniometer could identify the optimal thickness that, when implanted, provides high postoperative function. In twenty-two patients that underwent unrestricted caliper-verified kinematic alignment (KA) with a PCL retaining implant, two surgeons measured tibial orientation in extension and 90° flexion with 10, 11, 12, and 13 mm thick insert goniometers. Each TKA had one insert thickness that restored either the maximum external tibial orientation in extension, the maximum internal tibial orientation at 90° flexion, or both relative to 1 mm thinner and thicker inserts. In addition, the 6-month median [interquartile range] Forgotten Joint Score of 73 (54-87) and Oxford Knee Score of 42 (38-45) indicated high satisfaction and function. In conclusion, surgeons using a medial ball-in-socket TKA design can measure external tibial orientation in extension and internal tibial orientation at 90° flexion with an insert goniometer. Furthermore, implanting an insert with the thickness that provided the maximum orientation values resulted in high postoperative function, thereby personalizing PCL tension.}, language = {en} } @article{NedopilHowellHull2022, author = {Nedopil, Alexander J. and Howell, Stephen M. and Hull, Maury L.}, title = {A TKA insert with a lateral flat articular surface maximizes external and internal tibial orientations without anterior lift-off relative to low- and ultracongruent surfaces}, series = {Journal of Personalized Medicine}, volume = {12}, journal = {Journal of Personalized Medicine}, number = {8}, issn = {2075-4426}, doi = {10.3390/jpm12081274}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-286142}, year = {2022}, abstract = {Background: In total knee arthroplasty (TKA), inserts can have different levels of medial and lateral congruency determined by the acuteness of the upslopes of the anterior and posterior articular surfaces. The present study evaluated an insert with different levels of lateral congruency and a medial ball-in-socket congruency to test the hypothesis that a lateral flat (F) insert maximizes external tibial orientation at extension and internal orientation at 90° flexion and lowers the incidence of anterior lift-off relative to low-congruent (LC) and ultracongruent (UC) lateral inserts. Methods: Two surgeons treated 23 patients with unrestricted caliper-verified kinematic alignment (KA) and posterior cruciate ligament (PCL) retention. They randomly trialed inserts with a medial radial dial that functioned as a built-in goniometer by measuring the tibial orientation relative to a sagittal line on the femoral trial component. Anterior lift-off of the insert from the baseplate indicated PCL tightness. Results: The F insert's mean of 9° of external tibial orientation was higher than that of the LC (5°, p < 0.0001) and UC inserts (2°, p < 0.0001). The -13° of internal tibial orientation at 90° flexion was higher than that of the LC (-9°, p < 0.0001) and UC inserts (-7°, p < 0.0001). The 0\% incidence of anterior lift-off was less than that of the LC (26\%) and UC inserts (57\%) (p < 0.0001). Conclusions: Surgeons and implant manufacturers should know that adding congruency to the lateral articular surface limits external tibial orientation in extension and internal tibial orientation at 90° flexion and overtightens the PCL. These rotational limitations and flexion space tightness can adversely affect patellofemoral tracking and knee flexion.}, language = {en} } @article{WangStoecklLietal.2022, author = {Wang, Chenglong and St{\"o}ckl, Sabine and Li, Shushan and Herrmann, Marietta and Lukas, Christoph and Reinders, Yvonne and Sickmann, Albert and Gr{\"a}ssel, Susanne}, title = {Effects of extracellular vesicles from osteogenic differentiated human BMSCs on osteogenic and adipogenic differentiation capacity of na{\"i}ve human BMSCs}, series = {Cells}, volume = {11}, journal = {Cells}, number = {16}, issn = {2073-4409}, doi = {10.3390/cells11162491}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-286112}, year = {2022}, abstract = {Osteoporosis, or steroid-induced osteonecrosis of the hip, is accompanied by increased bone marrow adipogenesis. Such a disorder of adipogenic/osteogenic differentiation, affecting bone-marrow-derived mesenchymal stem cells (BMSCs), contributes to bone loss during aging. Here, we investigated the effects of extracellular vesicles (EVs) isolated from human (h)BMSCs during different stages of osteogenic differentiation on the osteogenic and adipogenic differentiation capacity of na{\"i}ve (undifferentiated) hBMSCs. We observed that all EV groups increased viability and proliferation capacity and suppressed the apoptosis of na{\"i}ve hBMSCs. In particular, EVs derived from hBMSCs at late-stage osteogenic differentiation promoted the osteogenic potential of na{\"i}ve hBMSCs more effectively than EVs derived from na{\"i}ve hBMSCs (na{\"i}ve EVs), as indicated by the increased gene expression of COL1A1 and OPN. In contrast, the adipogenic differentiation capacity of na{\"i}ve hBMSCs was inhibited by treatment with EVs from osteogenic differentiated hBMSCs. Proteomic analysis revealed that osteogenic EVs and na{\"i}ve EVs contained distinct protein profiles, with pro-osteogenic and anti-adipogenic proteins encapsulated in osteogenic EVs. We speculate that osteogenic EVs could serve as an intercellular communication system between bone- and bone-marrow adipose tissue, for transporting osteogenic factors and thus favoring pro-osteogenic processes. Our data may support the theory of an endocrine circuit with the skeleton functioning as a ductless gland.}, language = {en} } @article{StratosBehrendtAnselmetal.2022, author = {Stratos, Ioannis and Behrendt, Ann-Kathrin and Anselm, Christian and Gonzalez, Aldebarani and Mittlmeier, Thomas and Vollmar, Brigitte}, title = {Inhibition of TNF-α restores muscle force, inhibits inflammation, and reduces apoptosis of traumatized skeletal muscles}, series = {Cells}, volume = {11}, journal = {Cells}, number = {15}, issn = {2073-4409}, doi = {10.3390/cells11152397}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-286094}, year = {2022}, abstract = {Background: Muscle injuries are common in humans and are often associated with irrecoverable damage and disability. Upon muscle injury, TNF-α signaling pathways modulate the healing process and are predominantly associated with tissue degradation. In this study we assumed that TNF-α inhibition could reduce the TNF-α-associated tissue degradation after muscle injury. Materials and methods: Therefore, the left soleus muscle of 42 male Wistar rats was injured using a standardized open muscle injury model. All rats were treated immediately after injury either with infliximab (single i.p. injection; 10 mg/kg b.w.) or saline solution i.p. Final measurements were conducted at day one, four, and 14 post injury. The muscle force, the muscle cell proliferation, the muscle cell coverage as well as the myofiber diameter served as read out parameters of our experiment. Results: Systemic application of infliximab could significantly reduce the TNF-α levels in the injured muscle at day four upon trauma compared to saline treated animals. The ratio of muscle weight to body weight was increased and the twitch muscle force showed a significant rise 14 days after trauma and TNF-α inhibition. Quantification of myofiber diameter in the penumbra zone showed a significant difference between both groups at day one and four after injury, indicated by muscle hypertrophy in the infliximab group. Planimetric analysis of the injured muscle at day 14 revealed increased muscle tissue fraction in the infliximab group compared to the control animals. Muscle cell proliferation did not differ between both groups. Conclusions: These data provide evidence that the TNF-α blockade positively regulates the restauration of skeletal muscles upon injury.}, language = {en} } @phdthesis{PaulusverhRehling2023, author = {Paulus [verh. Rehling], Sofia}, title = {CRISPR/Cas9-basierte Etablierung Alkalischer Phosphatase-defizienter odontogener Zelllinien zur Analyse der dentalen Aspekte der Hypophosphatasie}, doi = {10.25972/OPUS-24349}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-243491}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Die Hypophosphatasie (HPP) ist eine seltene Erberkrankung, welche durch compound-heterozygote oder dominant negative heterozygote Mutationen des ALPL Gens zu einem Funktionsverlust der gewebeunspezifischen Alkalischen Phosphatase (TNAP) f{\"u}hrt. Die daraus resultierenden Mineralisierungsst{\"o}rungen betreffen sowohl den Knochen als auch in milderen Auspr{\"a}gungsformen die Z{\"a}hne und den Zahnhalteapparat. Das zahnmedizinische Leitsymptom und in vielen F{\"a}llen das erste Anzeichen der HPP ist dabei der vorzeitige Verlust der Milchz{\"a}hne ohne physiologische Wurzelresorption. Im Rahmen dieser Arbeit wurden verschiedene TNAP defiziente immortalisierte Zellen des parodontalen Ligaments (PDL) mittels der CRISPR/Cas9 Methode generiert und anschließend f{\"u}nf Zelllinien charakterisiert. Die dabei entstandenen Mutationen variierten von einer moderaten heterozygoten Punktmutation zu einer schwerwiegenden homozygoten Deletion eines einzelnen Nukleotids, welche in einem vorzeitigen Stopcodon resultierte. Analysen der ALPL Expression (qPCR), TNAP Aktivit{\"a}tsmessungen (CSPD Assay) und TNAP F{\"a}rbungen zeigten einen signifikanten R{\"u}ckgang in allen TNAP-defizienten Zelllinien mit einer starken Korrelation zwischen der Restaktivit{\"a}t und dem Ausmaß der Mutation, welche in Einklang mit der komplexen Genotyp-Ph{\"a}notyp Korrelation bei HPP zu bringen ist. Das Potential der osteogenen Differenzierung der hTERT PDL Zellen wurde in der homozygot mutierten Zelllinie komplett unterdr{\"u}ckt. M{\"o}gliche Mechanismen des vorzeitigen Zahnverlustes bei HPP Patienten ist die geminderte Formation und Mineralisation des Wurzelzements und die fehlerhafte Insertion der parodontalen Fasern. Die hier erstmalig etablierten Zellkulturmodelle liefern ein valides spenderunabh{\"a}ngiges in vitro Modell der HPP, welches dazu beitragen kann, die molekularbiologischen Zusammenh{\"a}nge der dentalen Aspekte der Hypophosphatasie zu ergr{\"u}nden und daraus gegebenenfalls neue Therapieans{\"a}tze abzuleiten.}, subject = {Hypophosphatasie}, language = {de} } @phdthesis{Seiler2023, author = {Seiler, Jonas}, title = {Die Expression des Vitamin-D-Rezeptors und der 24-Hydroxylase in Knochenmetastasen unterschiedlicher Entit{\"a}t}, doi = {10.25972/OPUS-32182}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-321827}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Knochenmetastasen sind unter den drei h{\"a}ufigsten Manifestationsorten metastatischer Absiedelungen von fortgeschrittenen Tumorerkrankungen. Dabei sind insbesondere Patientinnen und Patienten mit Prostata- und Mammakarzinom von Knochenmetastasen betroffen. Diese Knochenmetastasen f{\"u}hren h{\"a}ufig zu einer deutlichen Verschlechterung der Lebensqualit{\"a}t und zu einer Begrenzung der Therapieoptionen auf lediglich palliative Ans{\"a}tze. Die biologisch aktive Form von Vitamin D3, 1,25(OH)2-Vitamin D3, zeigt in pr{\"a}klinischen Studien antiproliferative und differenzierende Effekte auf Tumorzellen (101, 102, 104), die haups{\"a}chlich durch die Bindung an den Vitamin D-Rezeptor (VDR) vermittelt werden. Dar{\"u}berhinaus konnte pr{\"a}klinisch gezeigt werden, dass eine niedrige Expression des VDRs, ligandenunabh{\"a}ngig, die Knochenmetastasierung und das Tumorwachstum beg{\"u}nstigt (118). Eine niedrige VDR-Expression ist in Prim{\"a}rtumoren in klinischen Studien mit aggressiven Tumoreigenschaften assoziiert (111, 113, 115) und kann zudem mit einer erh{\"o}hten/fr{\"u}heren oss{\"a}ren Metastasierung einhergehen (167). Zudem gibt es Hinweise auf einen dysregulierten 1,25(OH)2-Vitamin D3-Katabolismus durch eine erh{\"o}hte Expression des 1,25(OH)2-Vitamin D3 katabolisierenden Enzyms CYP24A1/24-Hydroxylase in prim{\"a}rem Tumorzellen (70, 121, 122). Durch die Untersuchungen der Prim{\"a}rtumoren ist damit zu hypothetisieren, dass die Expression des VDRs und von CYP24A1 bei der Tumorprogression und Knochenmetastasierung von Bedeutung sein k{\"o}nnte. Entsprechende Untersuchungen des VDRs und der 24-Hydroxylase in Knochenmetastasen fehlen allerdings. Deshalb wurde in dieser Arbeit die Expression des VDRs und von CYP24A1 in Knochenmetastasen unterschiedlicher Prim{\"a}rtumoren von 66 Patientinnen und Patienten untersucht und m{\"o}gliche Assoziationen mit aggressiven Tumoreigenschaften analysiert. Der VDR konnte sowohl im Zytoplasma als auch im Nukleus nachgewiesen werden, w{\"a}hrend CYP24A1 nur im Zytoplasma lokalisiert war. Dabei wiesen insgesamt 71 \% der Knochenmetastasen eine hohe VDR-Expression im Nukleus und 56 \% im Zytoplasma auf. 59 \% der Knochenmetastasen wiesen eine hohe Expression des VDRs insgesamt auf. CYP24A1 war ebenso in 59 \% der Knochenmetastasen hoch exprimiert. Bei der Auswertung des Zusammenhangs zwischen den TNM-Stadien und des Gradings zeigte sich ein nicht signifikanter Trend von schlecht differenzierten Tumoren hin zu einer niedrigeren nukle{\"a}ren VDR-Expression (p=0.07, siehe Abbildung 33). Bez{\"u}glich der T-Stadien zeigten sich keine Unterschiede der Expression des VDRs und von CYP24A1 in den Knochenmetastasen zwischen lokal fortgeschrittenen und kleinen Prim{\"a}rtumoren. Weiterhin hatten Patientinnen und Patienten mit Lymphknotenmetastasen tendenziell eine verminderte VDR- und auch CYP24A1-Expression in den Knochenmetastasen im Vergleich zu Patienten und Patientinnen ohne Lymphknotenmetastasen (pVDR=0.15, pCYP24A1=0.06, siehe Abbildung 35). Außerdem hatten Patientinnen und Patienten mit multiple metastasierten Tumoren eine signifikant niedrigere nukle{\"a}re VDR- und auch CYP24A1-Expression im Vergleich zu Patientinnen und Patienten mit ausschließlich oss{\"a}rer Metastasierung (pVDR=0.03, pCYP24A1=0.01, Abbildung 36). Die Proteinexpression des VDRs- und von CYP24A1 korrelierten signifikant (p=0.001). Somit konnte mit dieser Arbeit die Proteinexpression des VDRs und von CYP24A1 in Knochenmetastasen durch Immunhistologie nachgewiesen werden. Insgesamt wurde der VDR und CYP24A1 von Knochenmetastasen diverser Entit{\"a}t unterschiedlich stark exprimiert. Jedoch k{\"o}nnten insbesondere Patienten mit VDR-exprimierenden Knochenmetastasen von einer Vitamin D3-Supplementierung profitieren, die h{\"a}ufig einen 25-OH-Vitamin D3 Mangel zeigen (165, 166). Ebenso k{\"o}nnte eine Untersuchung auf einen niedrigen VDR-Status in Prim{\"a}rtumoren dabei helfen, Krebspatienten mit einem hohen Metastasierungsrisiko zu identifizieren. Allerdings sind weitere und gr{\"o}ßere Studien inbesondere mit Evaluation des gesamten Vitamin D-Metabolismus und -Signalwegs notwendig, um diesen Zusammenhang weiter zu untersuchen.}, subject = {Vitamin D3}, language = {de} } @article{RamirezRodriguezPereiraHerrmannetal.2021, author = {Ram{\´i}rez-Rodr{\´i}guez, Gloria Bel{\´e}n and Pereira, Ana Rita and Herrmann, Marietta and Hansmann, Jan and Delgado-L{\´o}pez, Jos{\´e} Manuel and Sprio, Simone and Tampieri, Anna and Sandri, Monica}, title = {Biomimetic mineralization promotes viability and differentiation of human mesenchymal stem cells in a perfusion bioreactor}, series = {International Journal of Molecular Sciences}, volume = {22}, journal = {International Journal of Molecular Sciences}, number = {3}, issn = {1422-0067}, doi = {10.3390/ijms22031447}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285804}, year = {2021}, abstract = {In bone tissue engineering, the design of 3D systems capable of recreating composition, architecture and micromechanical environment of the native extracellular matrix (ECM) is still a challenge. While perfusion bioreactors have been proposed as potential tool to apply biomechanical stimuli, its use has been limited to a low number of biomaterials. In this work, we propose the culture of human mesenchymal stem cells (hMSC) in biomimetic mineralized recombinant collagen scaffolds with a perfusion bioreactor to simultaneously provide biochemical and biophysical cues guiding stem cell fate. The scaffolds were fabricated by mineralization of recombinant collagen in the presence of magnesium (RCP.MgAp). The organic matrix was homogeneously mineralized with apatite nanocrystals, similar in composition to those found in bone. X-Ray microtomography images revealed isotropic porous structure with optimum porosity for cell ingrowth. In fact, an optimal cell repopulation through the entire scaffolds was obtained after 1 day of dynamic seeding in the bioreactor. Remarkably, RCP.MgAp scaffolds exhibited higher cell viability and a clear trend of up-regulation of osteogenic genes than control (non-mineralized) scaffolds. Results demonstrate the potential of the combination of biomimetic mineralization of recombinant collagen in presence of magnesium and dynamic culture of hMSC as a promising strategy to closely mimic bone ECM.}, language = {en} } @phdthesis{WeissenbergergebKunz2023, author = {Weissenberger [geb. Kunz], Manuela-Hermina}, title = {Adenoviraler Gentransfer von SOX9 zur chondrogenen Differenzierung von humanen mesenchymalen Stammzellen}, doi = {10.25972/OPUS-32122}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-321221}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Der adenovirale SOX9-Gentransfer induziert nach 3-w{\"o}chiger in vitro Pelletkultur die chondrogene Differenzierung humaner mesenchymaler Stammzellen in Pelletkultur wirksamer als der TGFB1 Gentransfer mit geringerer Chondrozytenhypertrophie. Eine solche Technologie k{\"o}nnte zuk{\"u}nftig in vivo die Bildung von stabilerem hyalinem Knorpelregeneratgewebe erm{\"o}glichen.}, subject = {Hyaliner Knorpel}, language = {de} } @phdthesis{Stroemsdoerfer2023, author = {Str{\"o}msd{\"o}rfer, Johanna}, title = {Einfluss von Vibrationstraining auf k{\"o}rperliche Leistungsf{\"a}higkeit, Alltagsaktivit{\"a}t und Lebensqualit{\"a}t von Patienten mit monoklonaler Gammopathie}, doi = {10.25972/OPUS-32089}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-320895}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Patienten mit monoklonaler Gammopathie unklarer Signifikanz haben ein erh{\"o}htes Risiko an einer Osteoporose, Knochenbr{\"u}chen oder einer reduzierten Leistungsf{\"a}higkeit zu leiden. Bisher hat sich noch keine Therapie zur Pr{\"a}vention dieser Komplikationen etabliert. Das Ziel unserer Studie war es, WBV als eine m{\"o}gliche Trainingsmethode zu pr{\"u}fen und den Einfluss auf die Fitness, Alltagsaktivit{\"a}t und Lebensqualit{\"a}t von Patienten mit monoklonaler Gammopathie zu untersuchen. Hierf{\"u}r haben 15 Probanden mit MGUS/SMM ein Trainingsprogramm {\"u}ber 3 bzw. 6 Monate mit zwei Trainingseinheiten pro Woche f{\"u}r jeweils 30 Minuten absolviert. Die k{\"o}rperliche Leistungsf{\"a}higkeit wurde anhand verschiedener Funktionstests sowie der Erhebung von K{\"o}rpermaßen betrachtet. Die Alltagsaktivit{\"a}t wurde mittels Fitnesstrackern untersucht. Anhand von 3 verschiedenen Frageb{\"o}gen wurde zudem der Einfluss auf die Lebensqualit{\"a}t der Probanden durch das Training ermittelt. Zusammenfassend zeigte sich eine deutliche Verbesserung der Fitness und Ausdauer der Probanden, die Alltagsaktivit{\"a}t und die Lebensqualit{\"a}t wurden nicht durch das Vibrationstraining beeinflusst.}, subject = {Vibrationstraining}, language = {de} } @article{EbertWeissenbergerBraunetal.2022, author = {Ebert, Regina and Weissenberger, Manuel and Braun, Clemens and Wagenbrenner, Mike and Herrmann, Marietta and M{\"u}ller-Deubert, Sigrid and Krug, Melanie and Jakob, Franz and Rudert, Maximilian}, title = {Impaired regenerative capacity and senescence-associated secretory phenotype in mesenchymal stromal cells from samples of patients with aseptic joint arthroplasty loosening}, series = {Journal of Orthopaedic Research}, volume = {40}, journal = {Journal of Orthopaedic Research}, number = {2}, doi = {10.1002/jor.25041}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-238963}, pages = {513 -- 523}, year = {2022}, abstract = {Aseptic loosening of total hip and knee joint replacements is the most common indication for revision surgery after primary hip and knee arthroplasty. Research suggests that exposure and uptake of wear by mesenchymal stromal cells (MSC) and macrophages results in the secretion of proinflammatory cytokines and local osteolysis, but also impaired cell viability and regenerative capacity of MSC. Therefore, this in vitro study compared the regenerative and differentiation capacity of MSC derived from patients undergoing primary total hip arthroplasty (MSCprim) to MSC derived from patients undergoing revision surgery after aseptic loosening of total hip and knee joint implants (MSCrev). Regenerative capacity was examined by measuring the cumulative population doubling (CPD) in addition to the number of passages until cells stopped proliferating. Osteogenesis and adipogenesis in monolayer cultures were assessed using histological stainings. Furthermore, RT-PCR was performed to evaluate the relative expression of osteogenic and adipogenic marker genes as well as the expression of markers for a senescence-associated secretory phenotype (SASP). MSCrev possessed a limited regenerative capacity in comparison to MSCprim. Interestingly, MSCrev also showed an impaired osteogenic and adipogenic differentiation capacity compared to MSCprim and displayed a SASP early after isolation. Whether this is the cause or the consequence of the aseptic loosening of total joint implants remains unclear. Future research should focus on the identification of specific cell markers on MSCprim, which may influence complication rates such as aseptic loosening of total joint arthroplasty to further individualize and optimize total joint arthroplasty.}, language = {en} } @article{WeiderSchlagenhaufSeefried2022, author = {Weider, Margareta and Schlagenhauf, Ulrich and Seefried, Lothar}, title = {Oral health status of adult hypophosphatasia patients: A cross-sectional study}, series = {Journal of Clinical Periodontology}, volume = {49}, journal = {Journal of Clinical Periodontology}, number = {12}, doi = {10.1111/jcpe.13718}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-293777}, pages = {1253 -- 1261}, year = {2022}, abstract = {Aim This study evaluated the oral health status of adult patients with hypophosphatasia (HPP). Materials and Methods Parameters of oral health assessment comprised decayed/missing/filled teeth (DMFT) index, probing pocket depth and clinical attachment level (CAL) as well as documentation of tooth loss and periodontal health status according to CCD/AAP criteria. Findings were compared with national reference data (DMS V survey) reporting oral health status in age-related controls. Within-group comparisons were made between the HPP patients harbouring one versus two alkaline phosphatase liver/bone/kidney type (ALPL) gene variants. Results Of 80 HPP patients (64 female) with a mean age of 46.4 years (range 24-78) and one (n = 55) or two (n = 18) variants (n = 7 lacking testing) within the ALPL gene, those with two variants displayed substantially higher tooth loss rate (14.0 ± 9.3) than those affected by only one ALPL variant (4.1 ± 5.4), who did not differ substantially from healthy DMS V controls. While DMFT score and severe periodontal diseases (PDs) of HPP patients with one variant only increased with progressing age, the two-variant sub-cohort age independently exhibited increased DMFT scores and a higher rate of severe PDs. Conclusions HPP patients affected by two variants of the ALPL gene exhibited a higher risk of periodontitis and tooth loss than the general population, while patients with one variant developed clinically relevant oral disease symptoms with progressing ageing.}, language = {en} } @article{KaiserBrambrinkBenditzetal.2022, author = {Kaiser, Moritz and Brambrink, Sara and Benditz, Achim and Achenbach, Leonard and Gehentges, Matthias and K{\"o}nig, Matthias Alexander}, title = {Increase in lower limb strength after multimodal pain management in patients with low back pain}, series = {Medicina}, volume = {58}, journal = {Medicina}, number = {7}, issn = {1648-9144}, doi = {10.3390/medicina58070837}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284264}, year = {2022}, abstract = {Background and Objectives: The aim of the present study was to evaluate the efficacy of a multimodal pain therapy (MPM) regarding the objective parameter muscle strength of segment-dependent lower limb muscle groups before and after such a treatment. Materials and Methods: 52 patients with a history of low back pain and/or leg pain received standardized multimodal pain management. Strength of segment indicating lower limb muscles were assessed for each patient before and after ten days of treatment by handheld dynamometry. Results: Overall strength increased significantly from 23.6 kg ± 6.6 prior to treatment to 25.4 ± 7.3 after treatment, p ≤ 0.001. All muscle groups significantly increased in strength with exception of great toe extensors. Conclusions: Despite lower basic strength values at the beginning of treatment, all investigated muscle groups, except for the great toe extensors, showed a significant increase of overall strength after completion of the multimodal pain management concept. Increased overall strength could help with avoiding further need of medical care by supporting patients' autonomy in daily life activities, as well as maintaining working abilities. Thus, our study is the first to show a significant positive influence on lower limb strength in patients with low back pain after a conservative MPM program.}, language = {en} } @article{LiedertNemitzHaffnerLuntzeretal.2020, author = {Liedert, Astrid and Nemitz, Claudia and Haffner-Luntzer, Melanie and Schick, Fabian and Jakob, Franz and Ignatius, Anita}, title = {Effects of estrogen receptor and Wnt signaling activation on mechanically induced bone formation in a mouse model of postmenopausal bone loss}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {21}, issn = {1422-0067}, doi = {10.3390/ijms21218301}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285487}, year = {2020}, abstract = {In the adult skeleton, bone remodeling is required to replace damaged bone and functionally adapt bone mass and structure according to the mechanical requirements. It is regulated by multiple endocrine and paracrine factors, including hormones and growth factors, which interact in a coordinated manner. Because the response of bone to mechanical signals is dependent on functional estrogen receptor (ER) and Wnt/β-catenin signaling and is impaired in postmenopausal osteoporosis by estrogen deficiency, it is of paramount importance to elucidate the underlying mechanisms as a basis for the development of new strategies in the treatment of osteoporosis. The present study aimed to investigate the effectiveness of the activation of the ligand-dependent ER and the Wnt/β-catenin signal transduction pathways on mechanically induced bone formation using ovariectomized mice as a model of postmenopausal bone loss. We demonstrated that both pathways interact in the regulation of bone mass adaption in response to mechanical loading and that the activation of Wnt/β-catenin signaling considerably increased mechanically induced bone formation, whereas the effects of estrogen treatment strictly depended on the estrogen status in the mice.}, language = {en} } @article{HerrmannHildebrandMenzeletal.2019, author = {Herrmann, Marietta and Hildebrand, Maria and Menzel, Ursula and Fahy, Niamh and Alini, Mauro and Lang, Siegmund and Benneker, Lorin and Verrier, Sophie and Stoddart, Martin J. and Bara, Jennifer J.}, title = {Phenotypic characterization of bone marrow mononuclear cells and derived stromal cell populations from human iliac crest, vertebral body and femoral head}, series = {International Journal of Molecular Sciences}, volume = {20}, journal = {International Journal of Molecular Sciences}, number = {14}, issn = {1422-0067}, doi = {10.3390/ijms20143454}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285054}, year = {2019}, abstract = {(1) In vitro, bone marrow-derived stromal cells (BMSCs) demonstrate inter-donor phenotypic variability, which presents challenges for the development of regenerative therapies. Here, we investigated whether the frequency of putative BMSC sub-populations within the freshly isolated mononuclear cell fraction of bone marrow is phenotypically predictive for the in vitro derived stromal cell culture. (2) Vertebral body, iliac crest, and femoral head bone marrow were acquired from 33 patients (10 female and 23 male, age range 14-91). BMSC sub-populations were identified within freshly isolated mononuclear cell fractions based on cell-surface marker profiles. Stromal cells were expanded in monolayer on tissue culture plastic. Phenotypic assessment of in vitro derived cell cultures was performed by examining growth kinetics, chondrogenic, osteogenic, and adipogenic differentiation. (3) Gender, donor age, and anatomical site were neither predictive for the total yield nor the population doubling time of in vitro derived BMSC cultures. The abundance of freshly isolated progenitor sub-populations (CD45-CD34-CD73+, CD45-CD34-CD146+, NG2+CD146+) was not phenotypically predictive of derived stromal cell cultures in terms of growth kinetics nor plasticity. BMSCs derived from iliac crest and vertebral body bone marrow were more responsive to chondrogenic induction, forming superior cartilaginous tissue in vitro, compared to those isolated from femoral head. (4) The identification of discrete progenitor populations in bone marrow by current cell-surface marker profiling is not predictive for subsequently derived in vitro BMSC cultures. Overall, the iliac crest and the vertebral body offer a more reliable tissue source of stromal progenitor cells for cartilage repair strategies compared to femoral head.}, language = {en} } @article{SchmalzlPlumhoffGilbertetal.2019, author = {Schmalzl, J. and Plumhoff, P. and Gilbert, F. and Gohlke, F. and Konrads, C. and Brunner, U. and Jakob, F. and Ebert, R. and Steinert, AF}, title = {The inflamed biceps tendon as a pain generator in the shoulder: A histological and biomolecular analysis}, series = {Journal of Orthopaedic Surgery}, volume = {27}, journal = {Journal of Orthopaedic Surgery}, number = {1}, doi = {10.1177/2309499018820349}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228611}, pages = {1-10}, year = {2019}, abstract = {Introduction: The long head of the biceps (LHB) is often resected in shoulder surgery. However, its contribution to inflammatory processes in the shoulder remains unclear. In the present study, inflamed and noninflamed human LHBs were comparatively characterized for features of inflammation. Materials and methods: Twenty-two resected LHB tendons were classified into inflamed (n = 11) and noninflamed (n = 11) samples. For histological examination, samples were stained with hematoxylin eosin, Azan, van Gieson, and Masson Goldner trichrome. Neuronal tissue was immunohistochemically visualized. In addition, specific inflammatory marker gene expression of primary LHB-derived cell cultures were analyzed. Results: Features of tendinopathy, such as collagen disorganization, infiltration by inflammatory cells, neovascularization, and extensive neuronal innervation were found in the tendinitis group. Compared to noninflamed samples, inflamed LHBs showed a significantly increased inflammatory marker gene expression Conclusion: Structural and biomolecular differences of both groups suggest that the LHB tendon acts as an important pain generator in the shoulder joint. These findings can, on the one hand, contribute to the understanding of the biomolecular genesis of LHB tendinitis and, on the other hand, provide possibilities for new therapeutic approaches.}, language = {en} } @phdthesis{Nuesslein2023, author = {N{\"u}sslein, Nicolai}, title = {Mobile Inlay versus Fixed Inlay: Ein Vergleich kurz- und mittelfristiger radiologischer Ergebnisse nach Prothesenimplantation im oberen Sprunggelenk}, doi = {10.25972/OPUS-31749}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-317496}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Prothesennahe osteolytische L{\"a}sionen in Form von Lyses{\"a}umen und Zysten sind wegen des Risikos einer aseptischen Lockerung mitunter die h{\"a}ufigsten Gr{\"u}nde f{\"u}r ein Prothesenversagen in der Sprunggelenkendoprothetik. Die Genese dieser osteolytischen L{\"a}sionen ist aktuell noch nicht abschließend gekl{\"a}rt, bei weitestgehender {\"U}bereinstimmung in der Literatur jedoch multifaktoriell. Die Dissertation befasst sich mit dem Vergleich des kurz- bis mittelfristigen radiologischen Outcomes zweier unterschiedlicher Spunggelenkendoprothesen, welche jedoch - bis auf die Befestigungsart des Inlays - nahezu baugleich sind. Dabei wurde {\"u}berpr{\"u}ft, ob die Befestigungsart des Inlays (mobil oder fixiert) einen Einfluss auf die Ausbildung periprothetischer Lyses{\"a}ume und Zysten im Nachbeobachtungszeitraum hat. Es erfolgte zudem ein Vergleich der Survival Rates beider Gruppen. Zu den j{\"a}hrlichen Nachbeobachtungszeitr{\"a}umen wurden die angefertigten R{\"o}ntgenbilder auf die Ausbildung von relevanten prothesennahen Zysten und Lyses{\"a}umen hin untersucht. Zusammenfassend ergab sich zwischen den beiden Gruppen in Hinsicht auf die Entstehung prothesennaher Zysten sowohl bez{\"u}glich der Gesamtzahl sowie des betroffenen Knochens kein signifikanter Unterschied, obwohl Zysten in der Gruppe mit mobilem Inlay insgesamt h{\"a}ufiger auftraten. Auch in Hinsicht auf die Entstehung von Lyses{\"a}umen gab es bez{\"u}glich der Gesamtzahl keinen signifikanten Unterschied. In der Gruppe mit fixiertem Inlay kamen allerdings prothesennahe Lyses{\"a}ume in der Tibia signifikant h{\"a}ufiger vor als in der Gruppe mit mobilem Inlay. In Hinsicht auf die Survival Rates zeigte sich ebenfalls kein signifikanter Unterschied. Weitere prospektive, randomisierte Studien mit gr{\"o}ßeren Patientenkollektiven und l{\"a}ngerem Followup werden n{\"o}tig sein, um im Verlauf einen zu erwartenden signifikanten Unterschied zwischen beiden Prothesengruppen bez{\"u}glich der Entstehung prothesennaher osteolytischer L{\"a}sionen und ein konsekutives Prothesenversagen feststellen zu k{\"o}nnen.}, subject = {Prothetik}, language = {de} } @article{BorojevićJaukovićKukoljetal.2022, author = {Borojević, Ana and Jauković, Aleksandra and Kukolj, Tamara and Mojsilović, Slavko and Obradović, Hristina and Trivanović, Drenka and Živanović, Milena and Zečević, Željko and Simić, Marija and Gobeljić, Borko and Vujić, Dragana and Bugarski, Diana}, title = {Vitamin D3 stimulates proliferation capacity, expression of pluripotency markers, and osteogenesis of human bone marrow mesenchymal stromal/stem cells, partly through SIRT1 signaling}, series = {Biomolecules}, volume = {12}, journal = {Biomolecules}, number = {2}, issn = {2218-273X}, doi = {10.3390/biom12020323}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262203}, year = {2022}, abstract = {The biology of vitamin D3 is well defined, as are the effects of its active metabolites on various cells, including mesenchymal stromal/stem cells (MSCs). However, the biological potential of its precursor, cholecalciferol (VD3), has not been sufficiently investigated, although its significance in regenerative medicine — mainly in combination with various biomaterial matrices — has been recognized. Given that VD3 preconditioning might also contribute to the improvement of cellular regenerative potential, the aim of this study was to investigate its effects on bone marrow (BM) MSC functions and the signaling pathways involved. For that purpose, the influence of VD3 on BM-MSCs obtained from young human donors was determined via MTT test, flow cytometric analysis, immunocytochemistry, and qRT-PCR. Our results revealed that VD3, following a 5-day treatment, stimulated proliferation, expression of pluripotency markers (NANOG, SOX2, and Oct4), and osteogenic differentiation potential in BM-MSCs, while it reduced their senescence. Moreover, increased sirtuin 1 (SIRT1) expression was detected upon treatment with VD3, which mediated VD3-promoted osteogenesis and, partially, the stemness features through NANOG and SOX2 upregulation. In contrast, the effects of VD3 on proliferation, Oct4 expression, and senescence were SIRT1-independent. Altogether, these data indicate that VD3 has strong potential to modulate BM-MSCs' features, partially through SIRT1 signaling, although the precise mechanisms merit further investigation.}, language = {en} } @phdthesis{Leucht2023, author = {Leucht, Maximilian}, title = {Charakterisierung der zellul{\"a}ren Signatur und Zusammensetzung von Knochenmarks-MSC aus osteoarthrotischen H{\"u}ften}, doi = {10.25972/OPUS-30543}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305434}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Die Coxarthrose ist eine h{\"a}ufige degenerative Erkrankung, deren Pr{\"a}valenz mit steigendem Lebensalter zunimmt. Durch die steigende Lebenserwartung der Bev{\"o}lkerung nimmt dementsprechend auch die Anzahl an Patienten mit Coxarthrose zu. Die Therapie besteht konservativ u.a. aus Physiotherapie und Analgesie. Reichen die konservativen Maßnahmen nicht aus, steht der totale Gelenkersatz in Form eine Totalendoprothese zur Verf{\"u}gung. Bisher gibt es keine regenerativen Therapien, die den arthrotisch degenerierten Gelenkknorpel ersetzen k{\"o}nnen. Durch die F{\"a}higkeit, sich in Knochen-, Fett- und Knorpelzellen zu differenzieren, ist in der Vergangenheit die mesenchymale Stammzelle in den Fokus der Forschung ger{\"u}ckt. Es wird vermutet, dass diese Stammzellpopulation das Potential besitzen k{\"o}nnte, den defekten Knorpel zu ersetzen. Diese Zellpopulation ist in vivo jedoch noch nicht ausreichend charakterisiert und es fehlen belastbare Daten, wie sich die (pathologische) Umgebung auf die MSC auswirkt. In den letzten Jahren sind diverse Populationen von MSC mit unterschiedlichen Eigenschaften entdeckt worden. Um die subchondralen Populationen aus arthrotischen H{\"u}ften genauer zu charakterisieren, wurde hier Reaming aus dem Acetabulum (ein bei der H{\"u}ft-TEP Implantation anfallendes chirurgisches Abfallprodukt) untersucht. Die enthaltenen Zellen wurden im Hinblick auf die zellul{\"a}re Signatur und donorenbezogenen Eigenschaften untersucht. Parameter, die untersucht wurden, waren das Alter, das Geschlecht, der BMI und der K\&L Score. Außerdem wurde die zellul{\"a}re Signatur anhand bestimmter Oberfl{\"a}chenmarker untersucht. Weiterhin wurden die isolierten und kultivierten MSC untersucht, ob sie sich bzgl. ihrer F{\"a}higkeit unterscheiden, sich in die adipogene bzw. osteogene Linie zu differenzieren. Eine Eigenschaft, die bisher bei allen Populationen von m{\"o}glichen MNC bzw. MSC nachgewiesen wurde, ist ihre F{\"a}higkeit Kolonien zu bilden - sog. CFU-F. Bei den durchgef{\"u}hrten Untersuchungen zeigte sich, dass aus allen erhaltenen Proben MSC in Form von CFU-F gewonnen werden konnten. Weiterhin waren alle Zellen in der Lage adipogen bzw. osteogen zu differenzieren. Signifikante Unterschiede in Bezug auf die Differenzierungseigenschaften konnten nicht festgestellt werden. Eine h{\"o}here CFU-F Bildung konnte aus dem Reaming von m{\"a}nnlichen Donoren nachgewiesen werden. Weiterhin konnte gezeigt werden, dass sich eine signifikant h{\"o}here Anzahl CD271-exprimierender Zellen im Reaming von m{\"a}nnlichen Donoren befand. Ebenfalls konnte eine signifikante Zunahme f{\"u}r CD45- CD13+ CD105+ Zellen mit steigendem BMI nachgewiesen werden. Durch diese umfassende Versuchsreihe konnte dargelegt werden, dass es in arthrotischen H{\"u}ften Unterschiede in der MSC Zahl im Vergleich der Geschlechter gibt und dass bestimmte Populationen von MSC mit steigendem BMI zunehmen. Um diese Ergebnisse einordnen zu k{\"o}nnen ist es in Zukunft notwendig zu untersuchen, ob diese Unterschiede allein durch die Arthrose bedingt sind oder ob dieser Unterschied auch im gesunden Knochenmark vorliegt.}, subject = {Mesenchymale Stromazelle}, language = {de} } @article{NedopilDhaliwalHowelletal.2022, author = {Nedopil, Alexander J. and Dhaliwal, Anand and Howell, Stephen M. and Hull, Maury L.}, title = {A surgeon that switched to unrestricted kinematic alignment with manual instruments has a short learning curve and comparable resection accuracy and outcomes to those of an experienced surgeon}, series = {Journal of Personalized Medicine}, volume = {12}, journal = {Journal of Personalized Medicine}, number = {7}, issn = {2075-4426}, doi = {10.3390/jpm12071152}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281842}, year = {2022}, abstract = {After starting an orthopedic practice, a surgeon with a fellowship in mechanically aligned (MA) TKA initiated this study to characterize their learning curve after they switched to unrestricted kinematic alignment (KA) TKA using manual instruments. Accordingly, the present study determined for the inexperienced (IE) surgeon the number of cases required to achieve consistent femoral resections and operating times, and whether the femoral resection accuracy, patient-reported outcome measures (PROMs), and component alignment were different from an experienced (E) surgeon. This prospective cohort study analyzed the IE surgeon's first 30 TKAs, all performed with KA, and 30 consecutive KA TKAs performed by an E surgeon. The resection accuracy or deviation was the calipered thickness of the distal and posterior medial and lateral femoral resections minus the planned resection thickness, which was the thickness of the corresponding condyle of the femoral component, minus 2 mm for cartilage wear, and 1 mm for the kerf of the blade. Independent observers recorded the femoral resection thickness, operative times, PROMs, and alignment. For each femoral resection, the deviation between three groups of patients containing ten consecutive KA TKAs, was either insignificant (p = 0.695 to 1.000) or within the 0.5 mm resolution of the caliper, which indicated no learning curve. More than three groups were needed to determine the learning curve for the operative time; however, the IE surgeon's procedure dropped to 77 min for the last 10 patients, which was 20 min longer than the E surgeon. The resection deviations of the IE and E surgeon were comparable, except for the posterolateral femoral resection, which the IE surgeon under-resected by a mean of -0.8 mm (p < 0.0001). At a mean follow-up of 9 and 17 months, the Forgotten Joint Score, Oxford Knee Score, KOOS, and the alignment of the components and limbs were not different between the IE and E surgeon (p ≥ 0.6994). A surgeon that switches to unrestricted KA with manual instruments can determine their learning curve by computing the deviation of the distal and posterior femoral resections from the planned resection. Based on the present study, an IE surgeon could have resection accuracy, post-operative patient outcomes, and component alignment comparable to an E surgeon.}, language = {en} } @article{Trivanović2022, author = {Trivanović, Drenka}, title = {Adult stem cells in aging}, series = {Journal of Personalized Medicine}, volume = {12}, journal = {Journal of Personalized Medicine}, number = {5}, issn = {2075-4426}, doi = {10.3390/jpm12050795}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-275226}, year = {2022}, abstract = {No abstract available}, language = {en} }