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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.
The AMADEUS score is not a sufficient predictor for functional outcome after high tibial osteotomy
(2023)
Purpose
The Area Measurement And Depth Underlying Structures (AMADEUS) classification system has been proposed as a valuable tool for magnetic resonance (MR)-based grading of preoperatively encountered chondral defects of the knee joint. However, the potential relationship of this novel score with clinical data was yet to determine. It was the primary intention of this study to assess the correlative relationship of the AMADEUS with patient reported outcome scores in patients undergoing medial open-wedge high tibial valgus osteotomy (HTO). Furthermore, the arthroscopic ICRS (International Cartilage Repair Society) grade evaluation was tested for correlation with the AMADEUS classification system.
Methods
This retrospective, monocentric study found a total of 70 individuals that were indicated for HTO due to degenerative chondral defects of the medial compartment between 2008 and 2019. A preoperative MR image as well as a pre-osteotomy diagnostic arthroscopy for ICRS grade evaluation was mandatory for all patients. The Knee Osteoarthritis Outcome Score (KOOS) including its five subscale scores (KOOS-ADL, KOOS-QOL, KOOS-Sports, KOOS-Pain, KOOS-Symptoms) was obtained preoperatively and at a mean follow-up of 41.2 ± 26.3 months. Preoperative chondral defects were evaluated using the AMADEUS classification system and the final AMADEUS scores were correlated with the pre- and postoperative KOOS subscale sores. Furthermore, arthroscopic ICRS defect severity was correlated with the AMADEUS classification system.
Results
There was a statistically significant correlation between the AMADEUS BME (bone marrow edema) subscore and the KOOS Symptoms subscore at the preoperative visit (r = 0.25, p = 0.04). No statistically significant monotonic association between the AMADEUS total score and the AMADEUS grade with pre- and postoperative KOOS subscale scores were found. Intraoperatively obtained ICRS grade did reveal a moderate correlative relation with the AMADEUS total score and the AMADEUS grade (r = 0.28, p = 0.02).
Conclusions
The novel AMADEUS classification system largely lacks correlative capacity with patient reported outcome measures in patients undergoing HTO. The MR tomographic appearance of bone marrow edema is the only parameter predictive of the clinical outcome at the preoperative visit.
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.
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.
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.
The treatment landscape in multiple myeloma (MM) is shifting from genotoxic drugs to immunotherapies. Monoclonal antibodies, immunoconjugates, T-cell engaging antibodies and CART cells have been incorporated into routine treatment algorithms, resulting in improved response rates. Nevertheless, patients continue to relapse and the underlying mechanisms of resistance remain poorly understood. While Impaired death receptor signaling has been reported to mediate resistance to CART in acute lymphoblastic leukemia, this mechanism yet remains to be elucidated in context of novel immunotherapies for MM. Here, we describe impaired death receptor signaling as a novel mechanism of resistance to T-cell mediated immunotherapies in MM. This resistance seems exclusive to novel immunotherapies while sensitivity to conventional anti-tumor therapies being preserved in vitro. As a proof of concept, we present a confirmatory clinical case indicating that the FADD/BID axis is required for meaningful responses to novel immunotherapies thus we report impaired death receptor signaling as a novel resistance mechanism to T-cell mediated immunotherapy in MM.
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.
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.
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.