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 - Scorcelletti, Matteo A1 - Kara, Serhan A1 - Zange, Jochen A1 - Jordan, Jens A1 - Semler, Oliver A1 - Schönau, Eckhard A1 - Rittweger, Jörn A1 - Ireland, Alex A1 - Seefried, Lothar T1 - Lower limb bone geometry in adult individuals with X-linked hypophosphatemia: an observational study JF - Osteoporosis International N2 - 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. KW - bone KW - femur KW - geometry KW - shape KW - XLH Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324655 VL - 33 IS - 7 ER - TY - JOUR A1 - Hörterer, Hubert A1 - Baumbach, Sebastian Felix A1 - Lemperle, Stefan A1 - Altenberger, Sebastian A1 - Gottschalk, Oliver A1 - Mehlhorn, Alexander Tobias A1 - Röser, Anke A1 - Walther, Markus T1 - Clinical outcome and concomitant injuries in operatively treated fractures of the lateral process of the talus JF - BMC Musculoskeletal Disorders N2 - 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. KW - fracture KW - snowboarder's ankle KW - snowboarder's fracture KW - lateral process of the talus Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-321207 VL - 20 ER - TY - THES A1 - Schiffmaier, Jana T1 - Parathormon als potentielle Therapiestrategie der Odonto-Hypophosphatasie - Untersuchungen in einem dentogenen \(in-vitro\)-Modell T1 - Parathyroid hormone as a potential therapeutic strategy for odonto-hypophosphatasia - investigations in a dentogenic \(in\) \(vitro\) model N2 - Hypophosphatasie (HPP) beschreibt eine seltene Erbkrankheit, die hauptsächlich durch heterozygote Mutationen im ALPL-Gen verursacht wird. Diese führen zu einer verminderten Aktivität der gewebeunspezifischen alkalischen Phosphatase (TNAP). Neben skelettalen Symptomen sind Zahnanomalien wie der vorzeitige Verlust von Milchzähnen ohne resorbierte Wurzel sowie eine gestörte Mineralisierung der Zahnhart-substanzen ein typisches Merkmal der HPP. Die zugrunde liegenden molekularen Mechanismen sind bisher noch nicht vollständig verstanden. In der vorliegenden Arbeit wurden Zelllinien des parodontalen Ligaments mit Mutationen im ALPL-Gen charakterisiert, um anschließend mögliche Therapiestrategien für 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-Färbung) 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 Präsenz von PTH in-vitro imitieren. Anschließend wurde die ALPL-Expression (qPCR) sowie TNAP-Aktivität (CSPD-Assay) ermittelt. Die basale TNAP-Expression war variabel und reichte vom völligen 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 extrazellulären ATP einher. Es zeigte sich ein unterschiedliches Mineralisierungspotenzial, das hauptsächlich das TNAP-Expressionsniveau in den verschiedenen Zelllinien widerspiegelt, während die PTH-Stimulation keine Wirkung auf die Differenzierung hatte. Im Gegensatz zu klinischen Beobachtungen deuten die Ergebnisse auf eine hohe Korrelation zwischen Genotyp und Phänotyp in-vitro hin, die in-vivo noch bestätigt werden müssen. Die Sequenzierung bestätigte, dass durch die Geneditierung keine Off-Target Mutationen aufgetreten sind, welche somit keinen limitierenden Faktor hinsichtlich der Differenzierungskapazität darstellen können. Die Stimulation mit PTH führte zwar nicht zu einer gesteigerten ALPL-Expression, doch konnte die TNAP-Aktivität in den ALPL-defizienten Zelllinien punktuell gesteigert werden und bildet somit eine solide Basis für weitere Experimente, die zur Therapieentwicklung für die Odonto-HPP beitragen können. N2 - Hypophosphatasia (HPP) describes a rare inherited disorder caused mainly by heterozygous mutations in the ALPL gene. These lead to impaired activity of tissue non-specific alkaline phosphatase (TNAP). In addition to skeletal symptoms, dental abnormalities such as premature loss of deciduous teeth without resorption of the roots and impaired mineralization of tooth hard tissues are typical features of HPP. The underlying molecular mechanisms are not yet fully understood. In the present study, cell lines of the periodontal ligament with mutations in the ALPL gene were characterized to subsequently investigate potential therapeutic strategies for HPP at the molecular level. As part of the basal characterization, the cell lines were analyzed with respect to TNAP expression (immunohistochemistry, Western blot), metabolic profile (ATP assay) and osteogenic differentiation potential (alizarin staining). Also of interest was whether off-target mutations resulted from CRISPR/Cas9-based gene editing. To investigate the molecular effects of Parathyroid Hormone (PTH), which can increase ALPL expression, two protocols were established that mimic continuous, short-term, and intermittent presence of PTH in-vitro. ALPL gene expression (qPCR), as well as TNAP activity (CSPD assay) were then determined. Basal TNAP expression was variable, ranging from complete absence in the cell lines with deletions to strong TNAP expression in the cell line with a heterogeneous point mutation. Low expression was associated with decreased cell proliferation as well as extracellular ATP. There was a differential mineralization potential mainly reflecting the TNAP expression level in the different cell lines, whereas PTH stimulation had no effect on differentiation. In contrast to clinical observations, the results indicate a high correlation between genotype and phenotype in-vitro, which remains to be confirmed in-vivo. Sequencing confirmed that no off-target mutations occurred as a result of gene editing, which thus cannot be a limiting factor with respect to differentiation capacity. Although stimulation with PTH did not result in increased ALPL expression, TNAP activity was selectively increased in the ALPL-deficient cell lines, providing a solid basis for further experiments that may contribute to therapy development for Odonto-HPP. KW - Hypophosphatasie KW - Alkalische Phosphatase KW - Parathormon KW - CRISPR/Cas-Methode KW - PTH KW - TNAP KW - Odonto-HPP Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-349152 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 -