@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} } @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{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{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{KippnichDuempertSchorscheretal.2022, author = {Kippnich, Maximilian and Duempert, Maximilian and Schorscher, Nora and Jordan, Martin C. and Kunz, Andreas S. and Meybohm, Patrick and Wurmb, Thomas}, title = {Simultaneous treatment of trauma patients in a dual room trauma suite with integrated movable sliding gantry CT system: an observational study}, series = {Scientific Reports}, volume = {12}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-022-20491-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299695}, year = {2022}, abstract = {The trauma center of the University Hospital Wuerzburg has developed an advanced trauma pathway based on a dual-room trauma suite with an integrated movable sliding gantry CT-system. This enables simultaneous CT-diagnostics and treatment of two trauma patients. The focus of this study was to investigate the quality of the concept based on defined outcome criteria in this specific setting (time from arrival to initiation of CT scan: tCT; time from arrival to initiation of emergency surgery: tES). We analyzed all trauma patients admitted to the hospital's trauma suite from 1st May 2019 through 29th April 2020. Two subgroups were defined: trauma patients, who were treated without a second trauma patient present (group 1) and patients, who were treated simultaneously with another trauma patient (group 2). Simultaneous treatment was defined as parallel arrival within a period of 20 min. Of 423 included trauma patients, 46 patients (10.9\%) were treated simultaneously. Car accidents were the predominant trauma mechanism in this group (19.6\% vs. 47.8\%, p < 0.05). Prehospital life-saving procedures were performed with comparable frequency in both groups (intubation 43.5\% vs. 39\%, p = 0.572); pleural drainage 3.2\% vs. 2.2\%, p = 0.708; cardiopulmonary resuscitation 5\% vs. 2.2\%, p = 0.387). At hospital admission, patients in group 2 suffered significantly more pain (E-problem according to Advanced Trauma Life Support principles©; 29.2\% vs. 45.7\%, p < 0.05). There were no significant differences in the clinical treatment (emergency procedures, vasopressor and coagulant therapy, and transfusion of red blood cells). tCT was 6 (4-10) minutes (median and IQR) in group 1 and 8 (5-15.5) minutes in group 2 (p = 0.280). tES was 90 (78-106) minutes in group 1 and 99 (97-108) minutes in group 2 (p = 0.081). The simultaneous treatment of two trauma patients in a dual-room trauma suite with an integrated movable sliding gantry CT-system requires a medical, organizational, and technical concept adapted to this special setting. Despite the oftentimes serious and life-threatening injuries, optimal diagnostic and therapeutic procedures can be guaranteed for two simultaneous trauma patients at an individual medical level in consistent quality.}, 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{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{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} } @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{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} } @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{ChaudryGrimmFriedbergeretal.2020, author = {Chaudry, Oliver and Grimm, Alexandra and Friedberger, Andreas and Kemmler, Wolfgang and Uder, Michael and Jakob, Franz and Quick, Harald H. and von Stengel, Simon and Engelke, Klaus}, title = {Magnetic Resonance Imaging and Bioelectrical Impedance Analysis to Assess Visceral and Abdominal Adipose Tissue}, series = {Obesity}, volume = {28}, journal = {Obesity}, number = {2}, doi = {10.1002/oby.22712}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213591}, pages = {277 -- 283}, year = {2020}, abstract = {Objective This study aimed to compare a state-of-the-art bioelectrical impedance analysis (BIA) device with two-point Dixon magnetic resonance imaging (MRI) for the quantification of visceral adipose tissue (VAT) as a health-related risk factor. Methods A total of 63 male participants were measured using a 3-T MRI scanner and a segmental, multifrequency BIA device. MRI generated fat fraction (FF) maps, in which VAT volume, total abdominal adipose tissue volume, and FF of visceral and total abdominal compartments were quantified. BIA estimated body fat mass and VAT area. Results Coefficients of determination between abdominal (r\(^{2}\) = 0.75) and visceral compartments (r\(^{2}\) = 0.78) were similar for both groups, but slopes differed by a factor of two. The ratio of visceral to total abdominal FF was increased in older men compared with younger men. This difference was not detected with BIA. MRI and BIA measurements of the total abdominal volume correlated moderately (r\(^{2}\) = 0.31-0.56), and visceral measurements correlated poorly (r\(^{2}\) = 0.13-0.44). Conclusions Visceral BIA measurements agreed better with MRI measurements of the total abdomen than of the visceral compartment, indicating that BIA visceral fat area assessment cannot differentiate adipose tissue between visceral and abdominal compartments in young and older participants.}, language = {en} } @article{vonHertzbergBoelchWagenbrennerArnholdtetal.2021, author = {von Hertzberg-Boelch, Sebastian Philipp and Wagenbrenner, Mike and Arnholdt, J{\"o}rg and Frenzel, Stephan and Holzapfel, Boris Michael and Rudert, Maximilian}, title = {Custom Made Monoflange Acetabular Components for the Treatment of Paprosky Type III Defects}, series = {Journal of Personalized Medicine}, volume = {11}, journal = {Journal of Personalized Medicine}, number = {4}, issn = {2075-4426}, doi = {10.3390/jpm11040283}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236513}, year = {2021}, abstract = {Purpose: Patient-specific, flanged acetabular components are used for the treatment of Paprosky type III defects during revision total hip arthroplasty (THA). This monocentric retrospective cohort study analyzes the outcome of patients treated with custom made monoflanged acetabular components (CMACs) with intra- and extramedullary iliac fixation. Methods: 14 patients were included who underwent revision THA with CMACs for the treatment of Paprosky type III defects. Mechanism of THA failure was infection in 4 and aseptic loosening in 10 patients. Seven patients underwent no previous revision, the other seven patients underwent three or more previous revisions. Results: At a mean follow-up of 35.4 months (14-94), the revision rate of the implant was 28.3\%. Additionally, one perioperative dislocation and one superficial wound infection occurred. At one year postoperatively, we found a significant improvement of the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score (p = 0.015). Postoperative radiographic analysis revealed good hip joint reconstruction with a mean leg length discrepancy of 3 mm (-8-20), a mean lateralization of the horizontal hip center of rotation of 8 mm (-8-35), and a mean proximalization of the vertical hip center of rotation of 6 mm (13-26). Radiolucency lines were present in 30\%. Conclusion: CMACs can be considered an option for the treatment of acetabular bone loss in revision THA. Iliac intra- and extramedullary fixation allows soft tissue-adjusted hip joint reconstruction and improves hip function. However, failure rates are high, with periprosthetic infection being the main threat to successful outcome.}, 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} } @article{WagenbrennerPokerHeinzetal.2022, author = {Wagenbrenner, Mike and Poker, Konrad and Heinz, Tizian and Herrmann, Marietta and Horas, Konstantin and Ebert, Regina and Mayer-Wagner, Susanne and Holzapfel, Boris M. and Rudert, Maximilian and Steinert, Andre F. and Weißenberger, Manuel}, title = {Mesenchymal stromal cells (MSCs) isolated from various tissues of the human arthritic knee joint possess similar multipotent differentiation potential}, series = {Applied Sciences}, volume = {12}, journal = {Applied Sciences}, number = {4}, issn = {2076-3417}, doi = {10.3390/app12042239}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262334}, year = {2022}, abstract = {(1) Background: The mesenchymal stromal cells (MSCs) of different tissue origins are applied in cell-based chondrogenic regeneration. However, there is a lack of comparability determining the most suitable cell source for the tissue engineering (TE) of cartilage. The purpose of this study was to compare the in vitro chondrogenic potential of MSC-like cells from different tissue sources (bone marrow, meniscus, anterior cruciate ligament, synovial membrane, and the infrapatellar fat pad removed during total knee arthroplasty (TKA)) and define which cell source is best suited for cartilage regeneration. (2) Methods: MSC-like cells were isolated from five donors and expanded using adherent monolayer cultures. Differentiation was induced by culture media containing specific growth factors. Transforming growth factor (TGF)-ß1 was used as the growth factor for chondrogenic differentiation. Osteogenesis and adipogenesis were induced in monolayer cultures for 27 days, while pellet cell cultures were used for chondrogenesis for 21 days. Control cultures were maintained under the same conditions. After, the differentiation period samples were analyzed, using histological and immunohistochemical staining, as well as molecularbiological analysis by RT-PCR, to assess the expression of specific marker genes. (3) Results: Plastic-adherent growth and in vitro trilineage differentiation capacity of all isolated cells were proven. Flow cytometry revealed the clear co-expression of surface markers CD44, CD73, CD90, and CD105 on all isolated cells. Adipogenesis was validated through the formation of lipid droplets, while osteogenesis was proven by the formation of calcium deposits within differentiated cell cultures. The formation of proteoglycans was observed during chondrogenesis in pellet cultures, with immunohistochemical staining revealing an increased relative gene expression of collagen type II. RT-PCR proved an elevated expression of specific marker genes after successful differentiation, with no significant differences regarding different cell source of native tissue. (4) Conclusions: Irrespective of the cell source of native tissue, all MSC-like cells showed multipotent differentiation potential in vitro. The multipotent differentiation capacity did not differ significantly, and chondrogenic differentiation was proven in all pellet cultures. Therefore, cell suitability for cell-based cartilage therapies and tissue engineering is given for various tissue origins that are routinely removed during total knee arthroplasty (TKA). This study might provide essential information for the clinical tool of cell harvesting, leading to more flexibility in cell availability.}, language = {en} } @article{StreckForstervonHertzbergBoelchetal.2022, author = {Streck, Laura Elisa and Forster, Johannes and von Hertzberg-Boelch, Sebastian Philipp and Reichel, Thomas and Rudert, Maximilian and Rueckl, Kilian}, title = {The role of synovial fluid aspiration in shoulder joint infections}, series = {BMC Musculoskeletal Disorders}, volume = {23}, journal = {BMC Musculoskeletal Disorders}, doi = {10.1186/s12891-022-05285-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300795}, year = {2022}, abstract = {Background Joint aspiration with analysis of synovial fluid white blood cell count (WBC) and microbiological culture is a widely established aspect in the diagnosis of shoulder joint infections (SJI). In case of a two stage revision for SJI, joint aspiration before re-/implantation of a total shoulder arthroplasty (TSA) was used to rule out persistent infection for years but its value is under debate. Shoulder specific data on all aspects is rare. The current study aims to answer the following research questions: Does joint aspiration have an insufficient predictive value in the diagnosis of SJI in (1) initial workup and (2) before definite arthroplasty with polymethylmethacrylate (PMMA)-Spacer in place? Methods This retrospective evaluation investigates 35 patients that were treated for SJI with a two staged implantation of a TSA after debridement and implantation of an PMMA-Spacer. Joint aspirations were performed preoperatively (PA) and before re-/implantation of the prosthesis while spacer was in place (interstage aspiration, IA). Samples were taken for microbiological culture and analysis of WBC. Sensitivity and specificity were calculated with reference to intraoperative microbiological samples. Receiver Operating Characteristic (ROC), Area-Under-Curve analysis (AUC) and calculation of the Youden index were performed to find optimum cut-off for WBC. Results The sensitivity of microbiological cultures from PA was 58.3\% and the specificity was 88.9\%. The mean WBC was 27,800 leucocytes/mm3 (range 400-96,300). The maximum Youden index (0.857) was a cut-off of 2600 leucocytes/mm3 with a sensitivity of 85.7\% and a specificity of 100.0\%. The sensitivity and specificity of IA were 0.0\% and 88.5\%, respectively. Conclusions Preoperative aspiration is likely to miss Cutibacteria spp. and CoNS and cannot rule out infection for sure. However, we recommend it for its advantages of targeted antibiotic therapy in case of germ identification. Empiric antibiotic therapy should cover Cutibacteria and CoNS even if aspiration showed negative microbiological cultures. In contrast, the diagnostic value of interstage aspiration does not qualify for its routine use.}, language = {en} } @article{BoelchStreckPlumhoffetal.2020, author = {Boelch, Sebastian Philipp and Streck, Laura Elisa and Plumhoff, Piet and Konrads, Christian and Gohlke, Frank and Rueckl, Kilian}, title = {Infection control and outcome of staged reverse shoulder arthroplasty for the management of shoulder infections}, series = {JSES International}, volume = {4}, journal = {JSES International}, doi = {10.1016/j.jseint.2020.08.012}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230620}, pages = {959-963}, year = {2020}, abstract = {Background The treatment of septic arthritis, caused by either hematogenous seeding, injections, or surgery, can be challenging. Staged reverse shoulder arthroplasty (RSA) with temporary implantation of an antibiotic-loaded spacer is widely accepted but still discussed controversially. This study investigated the shoulder-specific bacterial spectrum, infection control rate, functional outcome, and infection-free survival rate after staged RSA in the mid- to long-term follow-up. It was hypothesized that staged RSA would show a high infection-free survival rate. Methods A total of 39 patients treated with staged RSA for primary septic arthritis (n = 8), secondary infection (n = 8), or periprosthetic infection (n = 23) were retrospectively included. The infection control rate was calculated based on cultures taken intraoperatively at spacer removal and RSA implantation. Infection-free survival was defined as no revision due to infection. The minimum follow-up period for functional outcome assessment was 2 years (n = 14; mean, 76 months; range, 31-128 months). Results Cutibacterium (26\%) and coagulase-negative staphylococci (23\%) were the predominant pathogens. The infection control rate was 90\%. The cumulative infection-free survival rate was 91\% after 128 months. Follow-up examinations showed a mean Constant score of 48 (range, 7-85), a mean QuickDASH (short version of Disabilities of the Arm, Shoulder and Hand questionnaire) score of 40.0 (range, 11.4-93.3), and a mean pain score of 1.6 (range, 0-7). Conclusion Staged RSA implantation was confirmed to be a reliable treatment option for primary, secondary, and periprosthetic infections of the shoulder. The infection control rate and infection-free survival rate are satisfactory. However, patients and surgeons must be aware of functional impairment even after successful treatment of infections.}, language = {en} } @article{WeissenbergerWeissenbergerWagenbrenneretal.2020, author = {Weissenberger, Manuel and Weissenberger, Manuela H. and Wagenbrenner, Mike and Heinz, Tizian and Reboredo, Jenny and Holzapfel, Boris M. and Rudert, Maximilian and Groll, J{\"u}rgen and Evans, Christopher H. and Steinert, Andre F.}, title = {Different types of cartilage neotissue fabricated from collagen hydrogels and mesenchymal stromal cells via SOX9, TGFB1 or BMP2 gene transfer}, series = {PLoS One}, volume = {15}, journal = {PLoS One}, number = {8}, doi = {10.1371/journal.pone.0237479}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230494}, year = {2020}, abstract = {Objective As native cartilage consists of different phenotypical zones, this study aims to fabricate different types of neocartilage constructs from collagen hydrogels and human mesenchymal stromal cells (MSCs) genetically modified to express different chondrogenic factors. Design Human MSCs derived from bone-marrow of osteoarthritis (OA) hips were genetically modified using adenoviral vectors encoding sex-determining region Y-type high-mobility-group-box (SOX)9,transforming growth factor beta (TGFB) 1or bone morphogenetic protein (BMP) 2cDNA, placed in type I collagen hydrogels and maintained in serum-free chondrogenic media for three weeks. Control constructs contained unmodified MSCs or MSCs expressing GFP. The respective constructs were analyzed histologically, immunohistochemically, biochemically, and by qRT-PCR for chondrogenesis and hypertrophy. Results Chondrogenesis in MSCs was consistently and strongly induced in collagen I hydrogels by the transgenesSOX9,TGFB1andBMP2as evidenced by positive staining for proteoglycans, chondroitin-4-sulfate (CS4) and collagen (COL) type II, increased levels of glycosaminoglycan (GAG) synthesis, and expression of mRNAs associated with chondrogenesis. The control groups were entirely non-chondrogenic. The levels of hypertrophy, as judged by expression of alkaline phosphatase (ALP) and COL X on both the protein and mRNA levels revealed different stages of hypertrophy within the chondrogenic groups (BMP2>TGFB1>SOX9). Conclusions Different types of neocartilage with varying levels of hypertrophy could be generated from human MSCs in collagen hydrogels by transfer of genes encoding the chondrogenic factorsSOX9,TGFB1andBMP2. This technology may be harnessed for regeneration of specific zones of native cartilage upon damage.}, language = {en} }