TY - JOUR A1 - Kaltdorf, Martin A1 - Breitenbach, Tim A1 - Karl, Stefan A1 - Fuchs, Maximilian A1 - Kessie, David Komla A1 - Psota, Eric A1 - Prelog, Martina A1 - Sarukhanyan, Edita A1 - Ebert, Regina A1 - Jakob, Franz A1 - Dandekar, Gudrun A1 - Naseem, Muhammad A1 - Liang, Chunguang A1 - Dandekar, Thomas T1 - Software JimenaE allows efficient dynamic simulations of Boolean networks, centrality and system state analysis JF - Scientific Reports N2 - The signal modelling framework JimenaE simulates dynamically Boolean networks. In contrast to SQUAD, there is systematic and not just heuristic calculation of all system states. These specific features are not present in CellNetAnalyzer and BoolNet. JimenaE is an expert extension of Jimena, with new optimized code, network conversion into different formats, rapid convergence both for system state calculation as well as for all three network centralities. It allows higher accuracy in determining network states and allows to dissect networks and identification of network control type and amount for each protein with high accuracy. Biological examples demonstrate this: (i) High plasticity of mesenchymal stromal cells for differentiation into chondrocytes, osteoblasts and adipocytes and differentiation-specific network control focusses on wnt-, TGF-beta and PPAR-gamma signaling. JimenaE allows to study individual proteins, removal or adding interactions (or autocrine loops) and accurately quantifies effects as well as number of system states. (ii) Dynamical modelling of cell–cell interactions of plant Arapidopsis thaliana against Pseudomonas syringae DC3000: We analyze for the first time the pathogen perspective and its interaction with the host. We next provide a detailed analysis on how plant hormonal regulation stimulates specific proteins and who and which protein has which type and amount of network control including a detailed heatmap of the A.thaliana response distinguishing between two states of the immune response. (iii) In an immune response network of dendritic cells confronted with Aspergillus fumigatus, JimenaE calculates now accurately the specific values for centralities and protein-specific network control including chemokine and pattern recognition receptors. KW - cellular signalling networks KW - computer modelling Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313303 VL - 13 ER - TY - JOUR A1 - Stratos, Ioannis A1 - Rinas, Ingmar A1 - Schröpfer, Konrad A1 - Hink, Katharina A1 - Herlyn, Philipp A1 - Bäumler, Mario A1 - Histing, Tina A1 - Bruhn, Sven A1 - Müller-Hilke, Brigitte A1 - Menger, Michael D. A1 - Vollmar, Brigitte A1 - Mittlmeier, Thomas T1 - Effects on bone and muscle upon treadmill interval training in hypogonadal male rats JF - Biomedicines N2 - 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. KW - osteoporosis KW - muscle KW - force KW - bone KW - micro-CT KW - training Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-319266 SN - 2227-9059 VL - 11 IS - 5 ER - TY - JOUR A1 - Rak, Dominik A1 - Klann, Lukas A1 - Heinz, Tizian A1 - Anderson, Philip A1 - Stratos, Ioannis A1 - Nedopil, Alexander J. A1 - Rudert, Maximilian T1 - Influence of mechanical alignment on functional knee phenotypes and clinical outcomes in primary TKA: a 1-year prospective analysis JF - Journal of Personalized Medicine N2 - 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. KW - knee arthroplasty KW - mechanical alignment KW - clinical outcome KW - phenotype KW - level of evidence III KW - prospective study Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313646 SN - 2075-4426 VL - 13 IS - 5 ER - TY - JOUR A1 - Weber, Patrick A1 - Beck, Melina A1 - Klug, Michael A1 - Klug, Andreas A1 - Klug, Alexander A1 - Glowalla, Claudio A1 - Gollwitzer, Hans T1 - Survival of patient-specific unicondylar knee replacement JF - Journal of Personalized Medicine N2 - 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. KW - unicompartmental knee arthroplasty KW - osteoarthritis KW - patient-specific implant KW - partial knee arthroplasty KW - patient-specific instruments Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313650 SN - 2075-4426 VL - 13 IS - 4 ER - TY - JOUR A1 - Trivanovic, Drenka A1 - Volkmann, Noah A1 - Stoeckl, Magdalena A1 - Tertel, Tobias A1 - Rudert, Maximilian A1 - Giebel, Bernd A1 - Herrmann, Marietta T1 - Enhancement of immunosuppressive activity of mesenchymal stromal cells by platelet-derived factors is accompanied by apoptotic priming JF - Stem Cell Reviews and Reports N2 - 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. KW - hematoma KW - platelet-rich plasma KW - fibrin KW - mesenchymal stromal cells KW - immunomodulation KW - apoptosis KW - autophagy KW - senescence KW - extracellular vesicles KW - metabolism Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324669 VL - 19 IS - 3 ER - TY - JOUR A1 - Reppenhagen, Stephan A1 - Becker, Roland A1 - Kugler, Andreas A1 - John, Dominik A1 - Kopf, Sebastian A1 - Anetzberger, Hermann T1 - Hand dominance is not of significance in performing fundamental arthroscopic skills simulation training tasks JF - Arthroscopy, Sports Medicine, and Rehabilitation N2 - 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. KW - hand dominance KW - physical therapy KW - arthroscopic simulator training KW - rehabilitation KW - sports therapy KW - sports medicine KW - orthopedics Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350432 SN - 2666-061X VL - 5 IS - 5 ER - TY - JOUR A1 - Kroner-Weigl, Niklas A1 - Chu, Jin A1 - Rudert, Maximilian A1 - Alt, Volker A1 - Shukunami, Chisa A1 - Docheva, Denitsa T1 - Dexamethasone is not sufficient to facilitate tenogenic differentiation of dermal fibroblasts in a 3D organoid model JF - Biomedicines N2 - 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. KW - 3D organoids KW - dermal fibroblasts KW - dexamethasone KW - scaffold-free KW - tenogenic differentiation KW - tendon tissue engineering Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311234 SN - 2227-9059 VL - 11 IS - 3 ER - TY - JOUR A1 - Maichl, Daniela Simone A1 - Kirner, Julius Arthur A1 - Beck, Susanne A1 - Cheng, Wen-Hui A1 - Krug, Melanie A1 - Kuric, Martin A1 - Ade, Carsten Patrick A1 - Bischler, Thorsten A1 - Jakob, Franz A1 - Hose, Dirk A1 - Seckinger, Anja A1 - Ebert, Regina A1 - Jundt, Franziska T1 - Identification of NOTCH-driven matrisome-associated genes as prognostic indicators of multiple myeloma patient survival JF - Blood Cancer Journal N2 - No abstract available. KW - cancer microenvironment KW - myeloma Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357598 VL - 13 ER - TY - JOUR A1 - Heinz, Tizian A1 - Eidmann, Annette A1 - Jakuscheit, Axel A1 - Laux, Tino A1 - Rudert, Maximilian A1 - Stratos, Ioannis T1 - Demographics and trends for inbound medical tourism in Germany for orthopedic patients before and during the COVID-19 pandemic JF - International Journal of Environmental Research and Public Health N2 - 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. KW - inbound medical tourism KW - orthopedic surgery KW - Germany KW - COVID-19 KW - pandemic Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304955 SN - 1660-4601 VL - 20 IS - 2 ER - TY - JOUR A1 - Heinz, Tizian A1 - Eidmann, Annette A1 - Anderson, Philip A1 - Weißenberger, Manuel A1 - Jakuscheit, Axel A1 - Rudert, Maximilian A1 - Stratos, Ioannis T1 - Trends in computer-assisted surgery for total knee arthroplasty in Germany: an analysis based on the operative procedure classification system between 2010 to 2021 JF - Journal of Clinical Medicine N2 - 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. KW - robotic KW - TKA KW - knee replacement KW - computer navigation KW - Germany Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304879 SN - 2077-0383 VL - 12 IS - 2 ER -