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The accurate classification of bone tumours is crucial for guiding clinical decisions regarding treatment and follow-up. However, differentiating between various tumour types is challenging due to the rarity of certain entities, high intra-class variability, and limited training data in clinical practice. This study proposes a multimodal deep learning model that integrates clinical metadata and X-ray imaging to improve the classification of primary bone tumours. The dataset comprises 1,785 radiographs from 804 patients collected between 2000 and 2020, including metadata such as age, affected bone site, tumour position, and gender. Ten tumour types were selected, with histopathology or tumour board decisions serving as the reference standard., Methods: Our model is based on the NesT image classification model and a multilayer perceptron with a joint fusion architecture. Descriptive statistics included incidence and percentage ratios for discrete parameters, and mean, standard deviation, median, and interquartile range for continuous parameters., Results: The mean age of the patients was 33.62 ± 18.60 years, with 54.73% being male. Our multimodal deep learning model achieved 69.7% accuracy in classifying primary bone tumours, outperforming the Vision Transformer model by five percentage points. SHAP values indicated that age had the most substantial influence among the considered metadata., Conclusion: The joint fusion approach developed in this study, integrating clinical metadata and imaging data, outperformed state-of-the-art models in classifying primary bone tumours. The use of SHAP values provided insights into the impact of different metadata on the model's performance, highlighting the significant role of age. This approach has potential implications for improving diagnostic accuracy and understanding the influence of clinical factors in tumour classification., (© 2024. The Author(s).)

Background: Electromagnetic field therapy is gaining attention for its potential in treating bone disorders, with Extracorporeal Magnetotransduction Therapy (EMTT) emerging as an innovative approach. EMTT offers a higher oscillation frequency and magnetic field strength compared to traditional Pulsed Electromagnetic Field (PEMF) therapy, showing promise in enhancing fracture healing and non-union recovery. However, the mechanisms underlying these effects remain unclear., Results: This study demonstrates that EMTT significantly enhances osteoblast bone formation at multiple levels, from gene expression to extracellular matrix mineralization. Key osteoblastogenesis regulators, including SP7 and RUNX2, and bone-related genes such as COL1A1, ALPL, and BGLAP, were upregulated, with expression levels surpassing those of the control group by over sevenfold ( p < 0.001). Enhanced collagen synthesis and mineralization were confirmed by von Kossa and Alizarin Red staining, indicating increased calcium and phosphate deposition. Additionally, calcium imaging revealed heightened calcium influx, suggesting a cellular mechanism for EMTT's osteogenic effects. Importantly, EMTT did not compromise cell viability, as confirmed by live/dead staining and WST-1 assays., Conclusion: This study is the first to show that EMTT can enhance all phases of osteoblastogenesis and improve the production of critical mineralization components, offering potential clinical applications in accelerating fracture healing, treating osteonecrosis, and enhancing implant osseointegration.

Background and Aim: Patients with liver cirrhosis often face a grave threat from infected ascites (IA). However, a well-established prognostic model for this complication has not been established in routine clinical practice. Therefore, we aimed to assess mortality risk in patients with liver cirrhosis and IA., Methods: We conducted a retrospective study across three tertiary hospitals, enrolling 534 adult patients with cirrhotic liver and IA, comprising 465 with spontaneous bacterial peritonitis (SBP), 34 with bacterascites (BA), and 35 with secondary peritonitis (SP). To determine the attributable mortality risk linked to IA, these patients were matched with 122 patients with hydropic decompensated liver cirrhosis but without IA. Clinical, laboratory, and microbiological parameters were assessed for their relation to mortality using univariable analyses and a multivariable random forest model (RFM). Least absolute shrinkage and selection operator (Lasso) regression model was used to establish an easy-to-use mortality prediction score., Results: The in-hospital mortality risk was highest for SP (39.0%), followed by SBP (26.0%) and BA (25.0%). Besides illness severity markers, microbiological parameters, such as Candida spp., were identified as the most significant indicators for mortality. The Lasso model determined 15 parameters with corresponding scores, yielding good discriminatory power (area under the receiver operating characteristics curve = 0.89). Counting from 0 to 83, scores of 20, 40, 60, and 80 corresponded to in-hospital mortalities of 3.3%, 30.8%, 85.2%, and 98.7%, respectively., Conclusion: We developed a promising mortality prediction score for IA, highlighting the importance of microbiological parameters in conjunction with illness severity for assessing patient outcomes., (© 2024 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Femoral fractures are often considered lethal for adult horses because femur osteosynthesis is still a surgical challenge. For equine femur osteosynthesis, primary stability is essential, but the detailed physiological forces occurring in the hindlimb are largely unknown. The objective of this study was to create a numerical testing environment to evaluate equine femur osteosynthesis based on physiological conditions. The study was designed as a finite element analysis (FEA) of the femur using a musculoskeletal model of the loading situation in stance. Relevant forces were determined in the musculoskeletal model via optimization. The treatment of four different fracture types with an intramedullary nail was investigated in FEA with loading conditions derived from the model. The analyzed diaphyseal fracture types were a transverse (TR) fracture, two oblique fractures in different orientations (OB-ML: medial-lateral and OB-AP: anterior-posterior) and a "gap" fracture (GAP) without contact between the fragments. For the native femur, the most relevant areas of increased stress were located distally to the femoral head and proximally to the caudal side of the condyles. For all fracture types, the highest stresses in the implant material were present in the fracture-adjacent screws. Maximum compressive (-348 MPa) and tensile stress (197 MPa) were found for the GAP fracture, but material strength was not exceeded. The mathematical model was able to predict a load distribution in the femur of the standing horse and was used to assess the performance of internal fixation devices via FEA. The analyzed intramedullary nail and screws showed sufficient stability for all fracture types., (© 2024. The Author(s).)

Purpose: Gastrointestinal disorders frequently necessitate surgery involving intestinal resection and anastomosis formation, potentially leading to severe complications like anastomotic leakage (AL) which is associated with increased morbidity, mortality, and adverse oncologic outcomes. While extensive research has explored the biology of anastomotic healing, there is limited understanding of the biomechanical properties of gastrointestinal anastomoses, which was aimed to be unraveled in this study., Methods: An ex-vivo model was developed for the biomechanical analysis of 32 handsewn porcine end-to-end anastomoses, using interrupted and continuous suture techniques subjected to different flow models. While multiple cameras captured different angles of the anastomosis, comprehensive data recording of pressure, time, and temperature was performed simultaneously. Special focus was laid on monitoring time, location and pressure of anastomotic leakage (LP) and bursting pressures (BP) depending on suture techniques and flow models., Results: Significant differences in LP, BP, and time intervals were observed based on the flow model but not on the suture techniques applied. Interestingly, anastomoses at the insertion site of the mesentery exhibited significantly higher rates of leakage and bursting compared to other sections of the anastomosis., Conclusion: The developed ex-vivo model facilitated comparable, reproducible, and user-independent biomechanical analyses. Assessing biomechanical properties of anastomoses offers an advantage in identifying technical weak points to refine surgical techniques, potentially reducing complications like AL. The results indicate that mesenteric insertion serves as a potential weak spot for AL, warranting further investigations and refinements in surgical techniques to optimize outcomes in this critical area of anastomotic procedures., (© 2024. The Author(s).)

Background: Collarbone fracture is a common injury, particularly among athletes involved in contact sports and participating in endurance activities. Conventional treatment requires surgery and postoperative immobilization, resulting in an average return-to-sport timeframe of approximately 13 weeks. This case challenges the established treatment protocols, aiming to expedite recovery and enable a quicker resumption of high-intensity athletic activities., Case Presentation: A 24-year-old Caucasian athlete completed a Half-Ironman Triathlon (70.3) merely three weeks post-collarbone fracture. Utilizing Extracorporeal Magneto-Transduction Therapy (EMTT) alongside surgical intervention, the patient achieved accelerated healing and remarkable performance outcomes without encountering any adverse effects., Conclusions: The integration of EMTT into the treatment paradigm for bone fractures alters the traditional understanding of recovery timelines and rehabilitation strategies. This case highlights the potential benefits of electromagnetic wave therapy in expediting the healing process and enabling athletes to resume high-level sports activities at an earlier stage., (© 2024. The Author(s).)

Osteoarthritis of the knee, a widespread cause of knee disability, is commonly treated in orthopedics due to its rising prevalence. Lower extremity misalignment, pivotal in knee injury etiology and management, necessitates comprehensive mechanical alignment evaluation via frequently-requested weight-bearing long leg radiographs (LLR). Despite LLR's routine use, current analysis techniques are error-prone and time-consuming. To address this, we conducted a multicentric study to develop and validate a deep learning (DL) model for fully automated leg alignment assessment on anterior-posterior LLR, targeting enhanced reliability and efficiency. The DL model, developed using 594 patients' LLR and a 60%/10%/30% data split for training, validation, and testing, executed alignment analyses via a multi-step process, employing a detection network and nine specialized networks. It was designed to assess all vital anatomical and mechanical parameters for standard clinical leg deformity analysis and preoperative planning. Accuracy, reliability, and assessment duration were compared with three specialized orthopedic surgeons across two distinct institutional datasets (136 and 143 radiographs). The algorithm exhibited equivalent performance to the surgeons in terms of alignment accuracy (DL: 0.21 ± 0.18°to 1.06 ± 1.3°vs. OS: 0.21 ± 0.16°to 1.72 ± 1.96°), interrater reliability (ICC DL: 0.90 ± 0.05 to 1.0 ± 0.0 vs. ICC OS: 0.90 ± 0.03 to 1.0 ± 0.0), and clinically acceptable accuracy (DL: 53.9%-100% vs OS 30.8%-100%). Further, automated analysis significantly reduced analysis time compared to manual annotation (DL: 22 ± 0.6 s vs. OS; 101.7 ± 7 s, p ≤ 0.01). By demonstrating that our algorithm not only matches the precision of expert surgeons but also significantly outpaces them in both speed and consistency of measurements, our research underscores a pivotal advancement in harnessing AI to enhance clinical efficiency and decision-making in orthopaedics., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sebastian Siebenlist reports a relationship with Arthrosurface that includes: consulting or advisory. Sebastian Siebenlist reports a relationship with Medi Bayreuth that includes: consulting or advisory., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Importance: The present study provides a substantial contribution to literature, showing that patients with enterococcal bloodstream infections (BSI) have a lower survival rate than those with Escherichia coli ( E. coli ) bloodstream infections after adjusting for 17 limiting prognostic factors and excluding patients with a limited life expectancy [metastatic tumor disease, Charlson Comorbidity Index (CCI) (greater than or equal to) 5]. This difference in the 5-year long-term survival was mainly driven by Enterococcus faecium (ECFM) bloodstream infections, with vancomycin resistance not being a significant contributing factor. Our findings imply that E. faecium bloodstream infections seem to be an independent risk factor for poor long-term outcomes. As such, future research should confirm this relationship and prioritize investigating its causality through prospective studies., Competing Interests: The authors declare no conflict of interest.

Here we present the GyroTrainer, a bespoke mechatronic balance board system designed to trigger activation of the back muscles while the user engages in a balance-challenging game. The GyroTrainer uses admittance control coupled with an iterative learning approach so as to tailor the admittance control parameters, i.e. difficulty level, according to the user's skill. Our experimental evaluation demonstrated that an individualized admittance control stiffness could be identified for each user, which corresponds with a desired level of difficulty and increased back muscle activity. A first game implementation demonstrates the feasibility of utilizing the GyroTrainer system and the individually identified admittance control stiffness for gamification of back muscle training.

In this study, we developed and validated a robotic testbench to investigate the biomechanical compatibility of three total knee arthroplasty (TKA) configurations under different loading conditions, including varus-valgus and internal-external loading across defined flexion angles. The testbench captured force-torque data, position, and quaternion information of the knee joint. A cadaver study was conducted, encompassing a native knee joint assessment and successive TKA testing, featuring femoral component rotations at -5°, 0°, and +5° relative to the transepicondylar axis of the femur. The native knee showed enhanced stability in varus-valgus loading, with the +5° external rotation TKA displaying the smallest deviation, indicating biomechanical compatibility. The robotic testbench consistently demonstrated high precision across all loading conditions. The findings demonstrated that the TKA configuration with a +5° external rotation displayed the minimal mean deviation under internal-external loading, indicating superior joint stability. These results contribute meaningful understanding regarding the influence of different TKA configurations on knee joint biomechanics, potentially influencing surgical planning and implant positioning. We are making the collected dataset available for further biomechanical model development and plan to explore the 6 Degrees of Freedom (DOF) robotic platform for additional biomechanical analysis. This study highlights the versatility and usefulness of the robotic testbench as an instrumental tool for expanding our understanding of knee joint biomechanics.

In tendon transfer surgeries sufficient stability of the tenorrhaphy is essential. In addition to the choice of a suitable technique, adequate overlap of donor and recipient tendons must be ensured. The aim of this study was to investigate the tensile strength with regard to tendon overlap of a recently published tenorrhaphy, termed Woven-Fridén (WF) tenorrhaphy, which displayed higher tensile strength and lower bulk when compared to the established Pulvertaft technique. For this purpose, WF tenorrhaphies with 1.5 cm, 2 cm, and 3 cm tendon overlap were performed and subsequently tested for different biomechanical properties by tensile testing. Among others, the parameters of ultimate load and stiffness were collected. Native tendons served as controls. A formula was derived to quantify the relation between tendon overlap and ultimate load. We observed that sufficient tensile strength (mean ultimate load of 217 N) is already given with a 2 cm tendon overlap. In addition, with more than 3 cm overlap length only little additional tensile strength is to be expected as the calculated ultimate load of 4 cm overlap (397 N) is approaching the plateau of the maximal ultimate load of 435 N (native tendons)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Wachtel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: The number of primary total knee arthroplasties (TKA) is expected to rise constantly. For patients and healthcare providers, the early identification of risk factors therefore becomes increasingly fundamental in the context of precision medicine. Others have already investigated the detection of risk factors by conducting literature reviews and applying conventional statistical methods. Since the prediction of events has been moderately accurate, a more comprehensive approach is needed. Machine learning (ML) algorithms have had ample success in many disciplines. However, these methods have not yet had a significant impact in orthopaedic research. The selection of a data source as well as the inclusion of relevant parameters is of utmost importance in this context. In this study, a standardized approach for ML in TKA to predict complications during surgery and an irregular surgery duration using data from two German arthroplasty-specific registries was evaluated., Methods: The dataset is based on two initiatives of the German Society for Orthopaedics and Orthopaedic Surgery. A problem statement and initial parameters were defined. After screening, cleaning and preparation of these datasets, 864 cases of primary TKA (2016-2019) were gathered. The XGBoost algorithm was chosen and applied with a hyperparameter search, a cross validation and a loss weighting to cope with class imbalance. For final evaluation, several metrics (accuracy, sensitivity, specificity, AUC) were calculated., Results: An accuracy of 92.0%, sensitivity of 34.8%, specificity of 95.8%, and AUC of 78.0% were achieved for predicting complications in primary TKA and 93.4%, 74.0%, 96.3%, and 91.6% for predicting irregular surgery duration, respectively. While traditional statistics (correlation coefficient) could not find any relevant correlation between any two parameters, the feature importance revealed several non-linear outcomes., Conclusion: In this study, a feasible ML model to predict outcomes of primary TKA with very promising results was built. Complex correlations between parameters were detected, which could not be recognized by conventional statistical analysis. Arthroplasty-specific data were identified as relevant by the ML model and should be included in future clinical applications. Furthermore, an interdisciplinary interpretation as well as evaluation of the results by a data scientist and an orthopaedic surgeon are of paramount importance., Level of Evidence: Level IV., (© 2022. The Author(s).)

Background: Scaffolds for tissue engineering can be received by whole organ decellularization while maintaining the site-specific extracellular matrix and the vascular tree. One among other decellularization techniques is the perfusion-based method using specific agents e.g. SDS for the elimination of cellular components. While SDS can disrupt the composition of the extracellular matrix and impair the adherence and growth of site-specific cells there are indications that xenogeneic cell types may benefit from protein denaturation by using higher detergent concentrations. The aim of this work is to investigate the effect of two different SDS-concentrations (i.e. 0.66% and 3%) on the ability of human endothelial cells to adhere and proliferate in an acellular rat kidney scaffold., Material and Methods: Acellular rat kidney scaffold was obtained by perfusion-based decellularization through the renal artery using a standardized protocol including SDS at concentrations of 0.66% or 3%. Subsequently cell seeding was performed with human immortalized endothelial cells EA.hy 926 via the renal artery. Recellularized kidneys were harvested after five days of pressure-controlled dynamic culture followed sectioning, histochemical and immunohistochemical staining as well as semiquantitative analysis., Results: Efficacy of decellularization was verified by absence of cellular components as well as preservation of ultrastructure and adhesive proteins of the extracellular matrix. In semiquantitative analysis of recellularization, cell count after five days of dynamic culture more than doubled when using the gentle decellularization protocol with a concentration of SDS at 0.66% compared to 3%. Detectable cells maintained their endothelial phenotype and presented proliferative behavior while only a negligible fraction underwent apoptosis., Conclusion: Recellularization of acellular kidney scaffold with endothelial cells EA.hy 926 seeded through the renal artery benefits from gentle decellularization procedure. Because of that, decellularization with a SDS concentration at 0.66% should be preferred in further studies and coculture experiments., (© 2023. The Author(s).)

Ascitic fluid infection is a serious complication of liver cirrhosis. The distinction between the more common spontaneous bacterial peritonitis (SBP) and the less common secondary peritonitis in patients with liver cirrhosis is crucial due to the varying treatment approaches. This retrospective multicentre study was conducted in three German hospitals and analysed 532 SBP episodes and 37 secondary peritonitis episodes. Overall, >30 clinical, microbiological, and laboratory parameters were evaluated to identify key differentiation criteria. Microbiological characteristics in ascites followed by severity of illness and clinicopathological parameters in ascites were the most important predictors identified by a random forest model to distinguish between SBP and secondary peritonitis. To establish a point-score model, a least absolute shrinkage and selection operator (LASSO) regression model selected the ten most promising discriminatory features. By aiming at a sensitivity of 95% either to rule out or rule in SBP episodes, two cut-off scores were defined, dividing patients with infected ascites into a low-risk (score ≥ 45) and high-risk group (score < 25) for secondary peritonitis. Overall, the discrimination of secondary peritonitis from SBP remains challenging. Our univariable analyses, random forest model, and LASSO point score may help clinicians with the crucial differentiation between SBP and secondary peritonitis.

Background/aim: Common surgical treatment options for large focal chondral defects (FCDs) in the knee include microfracturing (MFX) and microdrilling (DRL). Despite numerous studies addressing MFX and DRL of FDCs, no in vivo study has focused on biomechanical analysis of repair cartilage tissue in critical size FCDs with different amounts of holes and penetration depths., Materials and Methods: Two round FCDs (d=6 mm) were created on the medial femoral condyle in 33 adult merino sheep. All 66 defects were randomly assigned to 1 control or 4 different study groups: 1) MFX1, 3 holes, 2 mm depth; 2) MFX2, 3 holes, 4 mm depth; 3) DRL1, 3 holes, 4 mm depth; and 4) DRL2, 6 holes, 4 mm depth. Animals were followed up for 1 year. Following euthanasia, quantitative optical analysis of defect filling was performed. Biomechanical properties were analysed with microindentation and calculation of the elastic modulus., Results: Quantitative assessment of defect filling showed significantly better results in all treatment groups compared to untreated FCDs in the control group (p<0.001), with the best results for DRL2 (84.2% filling). The elastic modulus of repair cartilage tissue in the DRL1 and DRL2 groups was comparable to the adjacent native hyaline cartilage, while significantly inferior results were identified in both MFX groups (MFX1: p=0.002; MFX2: p<0.001)., Conclusion: More defect filling and better biomechanical properties of the repair cartilage tissue were identified for DRL compared to MFX, with the best results for 6 holes and 4 mm of penetration depth. These findings are in contrast to the current clinical practice with MFX as the gold standard and suggest a clinical return to DRL., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

This study is aimed at assessing the distinctive features of patients with infected ascites and liver cirrhosis and developing a scoring system to allow for the accurate identification of patients not requiring abdominocentesis to rule out infected ascites. A total of 700 episodes of patients with decompensated liver cirrhosis undergoing abdominocentesis between 2006 and 2020 were included. Overall, 34 clinical, drug, and laboratory features were evaluated using machine learning to identify key differentiation criteria and integrate them into a point-score model. In total, 11 discriminatory features were selected using a Lasso regression model to establish a point-score model. Considering pre-test probabilities for infected ascites of 10%, 15%, and 25%, the negative and positive predictive values of the point-score model for infected ascites were 98.1%, 97.0%, 94.6% and 14.9%, 21.8%, and 34.5%, respectively. Besides the main model, a simplified model was generated, containing only features that are fast to collect, which revealed similar predictive values. Our point-score model appears to be a promising non-invasive approach to rule out infected ascites in clinical routine with high negative predictive values in patients with hydropic decompensated liver cirrhosis, but further external validation in a prospective study is needed.

Musculoskeletal malignancies are a rare type of cancer. Consequently, sufficient imaging data for machine learning (ML) applications is difficult to obtain. The main purpose of this review was to investigate whether ML is already having an impact on imaging-driven diagnosis of musculoskeletal malignancies and what the respective reasons for this might be. A scoping review was conducted by a radiologist, an orthopaedic surgeon and a data scientist to identify suitable articles based on the PRISMA statement. Studies meeting the following criteria were included: primary malignant musculoskeletal tumours, machine/deep learning application, imaging data or data retrieved from images, human/preclinical, English language and original research. Initially, 480 articles were found and 38 met the eligibility criteria. Several continuous and discrete parameters related to publication, patient distribution, tumour specificities, ML methods, data and metrics were extracted from the final articles. For the synthesis, diagnosis-oriented studies were further examined by retrieving the number of patients and labels and metric scores. No significant correlations between metrics and mean number of samples were found. Several studies presented that ML could support imaging-driven diagnosis of musculoskeletal malignancies in distinct cases. However, data quality and quantity must be increased to achieve clinically relevant results. Compared to the experience of an expert radiologist, the studies used small datasets and mostly included only one type of data. Key to critical advancement of ML models for rare diseases such as musculoskeletal malignancies is a systematic, structured data collection and the establishment of (inter)national networks to obtain substantial datasets in the future. KEY POINTS: • Machine learning does not yet significantly impact imaging-driven diagnosis for musculoskeletal malignancies compared to other disciplines such as lung, breast or CNS cancer. • Research in the area of musculoskeletal tumour imaging and machine learning is still very limited. • Machine learning in musculoskeletal tumour imaging is impeded by insufficient availability of data and rarity of the disease., (© 2022. The Author(s).)

Objectives: To develop and validate machine learning models to distinguish between benign and malignant bone lesions and compare the performance to radiologists., Methods: In 880 patients (age 33.1 ± 19.4 years, 395 women) diagnosed with malignant (n = 213, 24.2%) or benign (n = 667, 75.8%) primary bone tumors, preoperative radiographs were obtained, and the diagnosis was established using histopathology. Data was split 70%/15%/15% for training, validation, and internal testing. Additionally, 96 patients from another institution were obtained for external testing. Machine learning models were developed and validated using radiomic features and demographic information. The performance of each model was evaluated on the test sets for accuracy, area under the curve (AUC) from receiver operating characteristics, sensitivity, and specificity. For comparison, the external test set was evaluated by two radiology residents and two radiologists who specialized in musculoskeletal tumor imaging., Results: The best machine learning model was based on an artificial neural network (ANN) combining both radiomic and demographic information achieving 80% and 75% accuracy at 75% and 90% sensitivity with 0.79 and 0.90 AUC on the internal and external test set, respectively. In comparison, the radiology residents achieved 71% and 65% accuracy at 61% and 35% sensitivity while the radiologists specialized in musculoskeletal tumor imaging achieved an 84% and 83% accuracy at 90% and 81% sensitivity, respectively., Conclusions: An ANN combining radiomic features and demographic information showed the best performance in distinguishing between benign and malignant bone lesions. The model showed lower accuracy compared to specialized radiologists, while accuracy was higher or similar compared to residents., Key Points: • The developed machine learning model could differentiate benign from malignant bone tumors using radiography with an AUC of 0.90 on the external test set. • Machine learning models that used radiomic features or demographic information alone performed worse than those that used both radiomic features and demographic information as input, highlighting the importance of building comprehensive machine learning models. • An artificial neural network that combined both radiomic and demographic information achieved the best performance and its performance was compared to radiology readers on an external test set., (© 2022. The Author(s).)

Background: Bone biopsies are often necessary to make a diagnosis in the case of irregular bone structures of the jaw. A 3D-printed surgical guide may be a helpful tool for enhancing the accuracy of the biopsy and for ensuring that the tissue of interest is precisely removed for examination. This study was conducted to compare the accuracy of biopsies performed with 3D-printed surgical guides to that of free-handed biopsies., Methods: Computed tomography scans were performed on patients with bony lesions of the lower jaw. Surgical guides were planned via computer-aided design and manufactured by a 3D-printer. Biopsies were performed with the surgical guides. Bone models of the lower jaw with geometries identical to the patients' lower jaws were produced using a 3D-printer. The jaw models were fitted into a phantom head model and free-handed biopsies were taken as controls. The accuracy of the biopsies was evaluated by comparing the parameters for the axis, angle and depth of the biopsies to the planned parameters., Results: Eight patients were included. The mean deviation between the biopsy axes was significantly lower in guided procedures than in free-handed biopsies (1.4 mm ± 0.9 mm; 3.6 mm ± 1.0 mm; p = 0.0005). The mean biopsy angle deviation was also significantly lower in guided biopsies than in free-handed biopsies (6.8° ± 4.0; 15.4° ± 3.6; p = 0.0005). The biopsy depth showed no significant difference between the guided and the free-handed biopsies., Conclusions: Computer-guided biopsies allow significantly higher accuracy than free-handed procedures., (© 2022. The Author(s).)

This paper presents the application of an adaptive exoskeleton for finger rehabilitation. The system consists of a force-controlled exoskeleton of the finger and wireless coupling to a mobile application for the rehabilitation of complex regional pain syndrome (CRPS) patients. The exoskeleton has sensors for motion detection and force control as well as a wireless communication module. The proposed mobile application allows to interactively control the exoskeleton, store collected patient-specific data, and motivate the patient for therapy by means of gamification. The exoskeleton was applied to three CRPS patients over a period of six weeks. We present the design of the exoskeleton, the mobile application with its game content, and the results of the performed preliminary patient study. The exoskeleton system showed good applicability; recorded data can be used for objective therapy evaluation.

The closure of wounds and subsequent optimal wound healing is essential to any successful surgical intervention. Especially on parts of the body with limited possibilities for local reconstruction, optimal distribution of load is essential. The aim of the present study was therefore to examine three different incision patterns, conventional straight, Lazy-S and Zigzag, with regard to their biomechanical stability and mode of failure on a porcine skin model. Our results demonstrate the superior biomechanical stability of Lazy-S and Zigzag incision patterns with perpendicular suture placement. This holds true, in particular, for Zigzag incisions, which showed the highest values for all parameters assessed. Moreover, the observed superior stability of Lazy-S and Zigzag incision patterns was diminished when sutures were placed in tensile direction. The conventional straight incision represents the standard access for a large number of surgical procedures. However, we were able to demonstrate the superior biomechanical stability of alternative incision patterns, in particular the Zigzag incision. This is most likely caused by an improved distribution of tensile force across the wound due to the perpendicular placement of sutures. Moreover, this technique offers additional advantages, such as a better overview of the operated area as well as several cosmetic improvements. We therefore advocate that the surgeon should consider the use of a Zigzag incision over a conventional straight incision pattern.

Background: For several decades, scientific efforts have been taken to develop strategies and medical aids for the reduction of anastomotic complications after intestinal surgery. Still, anastomotic leakage (AL) represents a frequently occurring postoperative complication with serious consequences on health, quality of life, and economic aspects. Approaches using collagen and/or fibrin-based sealants to cover intestinal anastomoses have shown promising effects toward leak reduction; however, they have not reached routine use yet. To assess the effects of covering intestinal anastomoses with collagen and/or fibrin-based sealants on postoperative leakage, a systematic review and meta-analysis were conducted., Method: PubMed, Web of Science, Cochrane Library, and Scopus (01/01/1964 to 17/01/2022) were searched to identify studies investigating the effects of coating any intestinal anastomoses with collagen and/or fibrin-based sealants on postoperative AL, reoperation rates, Clavien-Dindo major complication, mortality, and hospitalization length. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated., Results: Overall, 15 studies (five randomized controlled trials, three nonrandomized intervention studies, six observational cohort studies) examining 1,387 patients in the intervention group and 2,243 in the control group were included. Using fixed-effects meta-analysis ( I 2  < 50%), patients with coated intestinal anastomoses presented significantly lower AL rates (OR = 0.37; 95% CI 0.27-0.52; p  < 0.00001), reoperation rates (OR, 0.21; 95% CI, 0.10-0.47; p  = 0.0001), and Clavien-Dindo major complication rates (OR, 0.54; 95% CI, 0.35-0.84; p  = 0.006) in comparison to controls, with results remaining stable in sensitivity and subgroup analyses (stratified by study design, age group, intervention used, location of anastomoses, and indication for surgery). The length of hospitalization was significantly shorter in the intervention group (weighted mean difference (WMD), -1.96; 95% CI, -3.21, -0.71; p  = 0.002) using random-effects meta-analysis ( I 2  ≥ 50%), especially for patients with surgery of upper gastrointestinal malignancy (WMD, -4.94; 95% CI, -7.98, -1.90; p  = 0.001)., Conclusion: The application of collagen-based laminar biomaterials or fibrin sealants on intestinal anastomoses can significantly reduce postoperative rates of AL and its sequelae. Coating of intestinal anastomoses could be a step toward effective and sustainable leak prevention. To assess the validity and robustness of these findings, further clinical studies need to be conducted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cira, Stocker, Reischl, Obermeier, Friess, Burgkart and Neumann.)

Background: Machine Learning (ML) in arthroplasty is becoming more popular, as it is perfectly suited for prediction models. However, results have been heterogeneous so far. We hypothesize that an accurate ML model for outcome prediction in THA must be able to compute arthroplasty-specific data. In this study, we evaluate a ML approach applying data from two German arthroplasty-specific registries to predict adverse outcomes after THA, after careful evaluations of ML algorithms, outcome and input variables by an interdisciplinary team of data scientists and surgeons., Methods: Data of 1217 cases of primary THA from a single center were derived from two German arthroplasty-specific registries between 2016 to 2019. The XGBoost algorithm was adjusted and applied. Accuracy, sensitivity, specificity and AUC were calculated., Results: For the prediction of complications, the ML algorithm achieved an accuracy of 80.3%, a sensitivity of 31.0%, a specificity of 89.4% and an AUC of 64.1%. For the prediction of surgery duration, the ML algorithm yielded an accuracy of 81.7%, a sensitivity of 58.2%, a specificity of 91.6% and an AUC of 89.1%. The feature importance indicated non-linear outcomes for age, height, weight and surgeon. No relevant linear correlations were found., Conclusion: The attunement of input and output data as well as the modifications of the ML algorithm permitted the development of a feasible ML model for the prediction of complications and surgery duration.

Vascular graft infections (VGI) are severe complications in prosthetic vascular surgery with an incidence ranging from 1 to 6%. In these cases, synthetic grafts are commonly used in combination with antimicrobial agents. Expanded polytetrafluoroethylene (ePTFE) is in clinical use as a synthetic graft material and shows promising results by influencing bacterial adhesion. However, the literature on antibiotic-bound ePTFE grafts is scarce. Gentamicin is a frequently used antibiotic for local treatment of surgical site infections, but has not been evaluated as antimicrobial agent on ePTFE grafts. In this study, we examine the antimicrobial efficacy and biocompatibility of novel types of gentamicin-coated ePTFE grafts in vitro. ePTFE grafts coated with gentamicin salt formulations with covalently-bound palmitate were evaluated in two drug concentrations (GP1.75% and GP3.5%). To investigate effects from types of formulations, also suspensions of gentamicin in palmitate as well as polylactide were used at comparable levels (GS + PA and GS + R203). Antibacterial efficacies were estimated by employing a zone of inhibition, growth inhibition and bacterial adhesion assay against Staphylococcus aureus (SA). Cytotoxicity was determined with murine fibroblasts according to the ISO standard 10993-5. Gentamicin-coated ePTFE grafts show low bacterial adherence and strong antibacterial properties in vitro against SA. Bactericidal inhibition lasted until day 11. Highest biocompatibility was achieved using gentamicin palmitate GP1.75% coated ePTFE grafts. ePTFE grafts with gentamicin-coating are effective in vitro against SA growth and adherence. Most promising results regarding antimicrobial properties and biocompatibility were shown with chemically bounded gentamicin palmitate GP1.75% coatings. Graphical abstract., (© 2022. The Author(s).)

Background/aim: Increasing economic pressure in modern healthcare necessitates an increase in efficiency in total knee arthroplasty (TKA) while maintaining high-quality outcomes. Removal of debris using pulsatile lavage (PL) during cement polymerization may considerably reduce the operative duration. However, water can penetrate the interface, resulting in impaired implant fixation. The aim of the present study was to investigate the impact of early-onset PL during bone cement polymerization on implant fixation and operative duration., Materials and Methods: Cemented implantation of tibial trays was performed in 20 fresh-frozen human tibiae from 10 donors in a matched-pair study design in two groups: 1) PL during cement polymerization; and 2) PL after completion of the polymerization process. The cement penetration depth was analysed by computed tomography (CT), and the pull-out force was measured to evaluate primary implant fixation. The duration of the procedure was recorded for both groups., Results: Comparable pull-out forces were observed in the experimental (2,213 N) and control groups (2,350 N; p=0.68). The mean depth of cement penetration was similar in both groups. PL during cement polymerization could decrease the operative duration by 10 min., Conclusion: The application of PL during cement polymerization could significantly reduce operative duration and had no adverse effect on the mechanical fixation of the tibial component., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Artificial intelligence (AI) in healthcare is rapidly growing and offers novel options of data analysis. Machine learning (ML) represents a distinct application of AI, which is capable of generating predictions and has already been tested in different medical specialties with various approaches such as diagnostic applications, cost predictions or identification of risk factors. In orthopaedics, this technology has only recently been introduced and the literature on ML in knee arthroplasty is scarce. In this review, we aim to investigate which predictions are already feasible using ML models in knee arthroplasty to identify prerequisites for the effective use of this novel approach. For this reason, we conducted a systematic review of ML algorithms for outcome prediction in knee arthroplasty., Methods: A comprehensive search of PubMed, Medline database and the Cochrane Library was conducted to find ML applications for knee arthroplasty. All relevant articles were systematically retrieved and evaluated by an orthopaedic surgeon and a data scientist on the basis of the PRISMA statement. The search strategy yielded 225 articles of which 19 were finally assessed as eligible. A modified Coleman Methodology Score (mCMS) was applied to account for a methodological evaluation., Results: The studies presented in this review demonstrated fair to good results (AUC median 0.76/range 0.57-0.98), while heterogeneous prediction models were analysed: complications (6), costs (4), functional outcome (3), revision (2), postoperative satisfaction (2), surgical technique (1) and biomechanical properties (1) were investigated. The median mCMS was 65 (range 40-80) points., Conclusion: The prediction of distinct outcomes with ML models applying specific data is already feasible; however, the prediction of more complex outcomes is still inaccurate. Registry data on knee arthroplasty have not been fully analysed yet so that specific parameters have not been sufficiently evaluated. The inclusion of specific input data as well as the collaboration of orthopaedic surgeons and data scientists are essential prerequisites to fully utilize the capacity of ML in knee arthroplasty. Future studies should investigate prospective data with specific and longitudinally recorded parameters., Level of Evidence: III., (© 2022. The Author(s).)

Purpose: Dislocated tibial avulsions of the posterior cruciate ligament (PCL) require surgical intervention. Several arthroscopic strategies are options to fix the fragment and restore posterior laxity, including two types of suspension button devices: adjustable (self-locking) and rigid knotted systems. Our hypothesis was that a rigid knotted button construct has superior biomechanical properties regarding laxity restoration compared with an adjustable system. Both techniques were compared with standard screw fixation and the native PCL., Methods: Sixty porcine knees were dissected. The constructs were tested for elongation, stiffness, yield force, load to failure force, and failure mode in a material testing machine. Group N (native, intact PCL) was used as a control group. In group DB (Dogbone™), TR (Tightrope™), and S (screw), a standardized block osteotomy with the osteotomized fragment attached to the PCL was set. The DB and TR groups simulated using a suspension button system with either a rigid knotted (DB) or adjustable system (TR). These groups were compared to a screw technique (S) simulating antegrade screw fixation from posterior., Results: Comparing the different techniques (DB, TR, S), no significant elongation was detected; all techniques achieved a sufficient posterior laxity restoration. Significant elongation in the DB and TR group was detected compared with the native PCL (N). In contrast, screw fixation did not lead to significant elongation. The stiffness, yield load, and load to failure force did not differ significantly between the techniques. None of the techniques reached the same level of yield load and load to failure force as the intact state., Conclusion: Arthroscopic suspension button techniques sufficiently restore the posterior laxity and gain a comparable construct strength as an open antegrade screw fixation., (© 2021. The Author(s).)

Background An artificial intelligence model that assesses primary bone tumors on radiographs may assist in the diagnostic workflow. Purpose To develop a multitask deep learning (DL) model for simultaneous bounding box placement, segmentation, and classification of primary bone tumors on radiographs. Materials and Methods This retrospective study analyzed bone tumors on radiographs acquired prior to treatment and obtained from patient data from January 2000 to June 2020. Benign or malignant bone tumors were diagnosed in all patients by using the histopathologic findings as the reference standard. By using split-sample validation, 70% of the patients were assigned to the training set, 15% were assigned to the validation set, and 15% were assigned to the test set. The final performance was evaluated on an external test set by using geographic validation, with accuracy, sensitivity, specificity, and 95% CIs being used for classification, the intersection over union (IoU) being used for bounding box placements, and the Dice score being used for segmentations. Results Radiographs from 934 patients (mean age, 33 years ± 19 [standard deviation]; 419 women) were evaluated in the internal data set, which included 667 benign bone tumors and 267 malignant bone tumors. Six hundred fifty-four patients were in the training set, 140 were in the validation set, and 140 were in the test set. One hundred eleven patients were in the external test set. The multitask DL model achieved 80.2% (89 of 111; 95% CI: 72.8, 87.6) accuracy, 62.9% (22 of 35; 95% CI: 47, 79) sensitivity, and 88.2% (67 of 76; CI: 81, 96) specificity in the classification of bone tumors as malignant or benign. The model achieved an IoU of 0.52 ± 0.34 for bounding box placements and a mean Dice score of 0.60 ± 0.37 for segmentations. The model accuracy was higher than that of two radiologic residents (71.2% and 64.9%; P = .002 and P < .001, respectively) and was comparable with that of two musculoskeletal fellowship-trained radiologists (83.8% and 82.9%; P = .13 and P = .25, respectively) in classifying a tumor as malignant or benign. Conclusion The developed multitask deep learning model allowed for accurate and simultaneous bounding box placement, segmentation, and classification of primary bone tumors on radiographs. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Carrino in this issue.

Recent studies conclude that a new technique for tendon transfers, the side-to-side tenorrhaphy by Fridén (FR) provides higher biomechanical stability than the established standard first described by Pulvertaft (PT). The aim of this study was to optimize side-to-side tenorrhaphies. We compared PT and FR tenorrhaphies as well as a potential improvement, termed Woven-Fridén tenorrhaphy (WF), with regard to biomechanical stability. Our results demonstrate superior biomechanical stability and lower bulk of FR and, in particular, WF over PT tenorrhaphies. The WF and FR technnique therefore seem to be a notable alternative to the established standard tenorrhaphy as they display lower bulk and higher stability, permitting successful immediate active mobilization after surgery., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: M. A. E. works as an instructor for Arthrex Inc educational courses on a fee basis. No further external funding, payments, or services have been received or will be received from a commercial party related directly or indirectly to the subject of this article. The authors alone are responsible for experiments, data analysis, and writing of the paper. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

This paper presents a novel mechatronic exoskeleton architecture for finger rehabilitation. The system consists of an underactuated kinematic structure that enables the exoskeleton to act as an adaptive finger stimulator. The exoskeleton has sensors for motion detection and control. The proposed architecture offers three main advantages. First, the exoskeleton enables accurate quantification of subject-specific finger dynamics. The configuration of the exoskeleton can be fully reconstructed using measurements from three angular position sensors placed on the kinematic structure. In addition, the actuation force acting on the exoskeleton is recorded. Thus, the range of motion (ROM) and the force and torque trajectories of each finger joint can be determined. Second, the adaptive kinematic structure allows the patient to perform various functional tasks. The force control of the exoskeleton acts like a safeguard and limits the maximum possible joint torques during finger movement. Last, the system is compact, lightweight and does not require extensive peripherals. Due to its safety features, it is easy to use in the home. Applicability was tested in three healthy subjects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Dickmann , Wilhelm, Glowalla , Haddadin , van der Smagt  and Burgkart .)

Due to the frequency of biofilm-forming Staphylococcus aureus and Staphylococcus epidermidis in orthopedics, it is crucial to understand the interaction between the soluble factors produced by prokaryotes and their effects on eukaryotes. Our knowledge concerning the effect of soluble biofilm factors (SBF) and their virulence potential on osteogenic differentiation is limited to few studies, particularly when there is no direct contact between prokaryotic and eukaryotic cells. SBF were produced by incubating biofilm from S. aureus and S. epidermidis in osteogenic media. Osteoblasts of seven donors were included in this study. Our results demonstrate that the detrimental effects of these pathogens do not require direct contact between prokaryotic and eukaryotic cells. SBF produced by S. aureus and S. epidermidis affect the metabolic activity of osteoblasts. However, the effect of SBF derived from S. aureus seems to be more pronounced compared to that of S. epidermidis. The influence of SBF of S. aureus and S. epidermidis on gene expression of COL1A1, ALPL, BGLAP, SPP1, RUNX2 is bacteria-, patient-, concentration-, and incubation time dependent. Mineralization was monitored by staining the calcium and phosphate deposition and revealed that the SBF of S. epidermidis markedly inhibits calcium deposition; however, S. aureus shows a less inhibitory effect. Therefore, these new findings support the hypotheses that soluble biofilm factors affect the osteogenic processes substantially, particularly when there is no direct interaction between bacteria and osteoblast., (© 2021. The Author(s).)

Background: With the onset of the COVID-19 pandemic at the beginning of 2020, the crucial role of hygiene in healthcare settings has once again become very clear. For diagnostic and for didactic purposes, standardized and reliable tests suitable to assess the competencies involved in "working hygienically" are required. However, existing tests usually use self-report questionnaires, which are suboptimal for this purpose. In the present study, we introduce the newly developed, competence-oriented HygiKo test instrument focusing health-care professionals' hygiene competence and report empirical evidence regarding its psychometric properties., Methods: HygiKo is a Situational Judgement Test (SJT) to assess hygiene competence. The HygiKo-test consists of twenty pictures (items), each item presents only one unambiguous hygiene lapse. For each item, test respondents are asked (1) whether they recognize a problem in the picture with respect to hygiene guidelines and, (2) if yes, to describe the problem in a short verbal response. Our sample comprised n = 149 health care professionals (79.1 % female; age: M = 26.7 years, SD = 7.3 years) working as clinicians or nurses. The written responses were rated by two independent raters with high agreement (α > 0.80), indicating high reliability of the measurement. We used Item Response Theory (IRT) for further data analysis., Results: We report IRT analyses that show that the HygiKo-test is suitable to assess hygiene competence and that it allows to distinguish between persons demonstrating different levels of ability for seventeen of the twenty items), especially for the range of low to medium person abilities. Hence, the HygiKo-SJT is suitable to get a reliable and competence-oriented measure for hygiene-competence., Conclusions: In its present form, the HygiKo-test can be used to assess the hygiene competence of medical students, medical doctors, nurses and trainee nurses in cross-sectional measurements. In order to broaden the difficulty spectrum of the current test, additional test items with higher difficulty should be developed. The Situational Judgement Test designed to assess hygiene competence can be helpful in testing and teaching the ability of working hygienically. Further research for validity is needed., (© 2021. The Author(s).)

In this study, topology optimized, patient specific osteosynthesis plates (TOPOS-implants) are evaluated for the mandibular reconstruction using fibula segments. These shape optimized implants are compared to a standard treatment with miniplates (thickness: 1.0 mm, titanium grade 4) in biomechanical testing using human cadaveric specimen. Mandible and fibula of 21 body donors were used. Geometrical models were created based on automated segmentation of CT-scans of all specimens. All reconstructions, including cutting guides for osteotomy as well as TOPOS-implants, were planned using a custom-made software tool. The TOPOS-implants were produced by electron beam melting (thickness: 1.0 mm, titanium grade 5). The fibula-reconstructed mandibles were tested in static and dynamic testing in a multi-axial test system, which can adapt to the donor anatomy and apply side-specific loads. Static testing was used to confirm mechanical similarity between the reconstruction groups. Force-controlled dynamic testing was performed with a sinusoidal loading between 60 and 240 N (reconstructed side: 30% reduction to consider resected muscles) at 5 Hz for up to 5 · 105 cycles. There was a significant difference between the groups for dynamic testing: All TOPOS-implants stayed intact during all cycles, while miniplate failure occurred after 26.4% of the planned loading (1.32 · 105 ± 1.46 · 105 cycles). Bone fracture occurred in both groups (miniplates: n = 3, TOPOS-implants: n = 2). A correlation between bone failure and cortical bone thickness in mandible angle as well as the number of bicortical screws used was demonstrated. For both groups no screw failure was detected. In conclusion, the topology optimized, patient specific implants showed superior fatigue properties compared to miniplates in mandibular reconstruction. Additionally, the patient specific shape comes with intrinsic guiding properties to support the reconstruction process during surgery. This demonstrates that the combination of additive manufacturing and topology optimization can be beneficial for future maxillofacial surgery., Competing Interests: The authors have declared that no competing interests exist. The affiliation Josefinum, and private practice for Oral and Maxillofacial Surgery at Pferseepark of JW does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The accuracy of computer-assisted biopsies at the lower jaw was compared to the accuracy of freehand biopsies., Methods: Patients with a bony lesion of the lower jaw with an indication for biopsy were prospectively enrolled. Two customized bone models per patient were produced using a 3D printer. The models of the lower jaw were fitted into a phantom head model to simulate operation room conditions. Biopsies for the study group were taken by means of surgical guides and freehand biopsies were performed for the control group., Results: The deviation of the biopsy axes from the planning was significantly less when using templates. It turned out to be 1.3 ± 0.6 mm for the biopsies with a surgical guide and 3.9 ± 1.1 mm for the freehand biopsies., Conclusions: Surgical guides allow significantly higher accuracy of biopsies. The preliminary results are promising, but clinical evaluation is necessary.

Recent years have seen an increasing number of genetically engineered pig models of human diseases including cancer. We previously generated pigs with a modified TP53 allele that carries a Cre-removable transcriptional stop signal in intron 1, and an oncogenic mutation TP53 R167H (orthologous to human TP53 R175H ) in exon 5. Pigs with the unrecombined mutant allele (flTP53 R167H ) develop mainly osteosarcoma but also nephroblastomas and lymphomas. This observation suggested that TP53 gene dysfunction is itself the key initiator of bone tumorigenesis, but raises the question which aspects of the TP53 regulation lead to the development of such a narrow tumour spectrum. Molecular analysis of p53 revealed the presence of two internal TP53 promoters (Pint and P2) equivalent to those found in human. Consequently, both pig and human express TP53 isoforms. Data presented here strongly suggest that P2-driven expression of the mutant R167H-Δ152p53 isoform (equivalent to the human R175H-Δ160p53 isoform) and its circular counterpart circTP53 determine the tumour spectrum and play a critical role in the malignant transformation in flTP53 R167H pigs. The detection of Δ152p53 isoform mRNA in serum is indicative of tumorigenesis. Furthermore, we showed a tissue-specific p53-dependent deregulation of the p63 and p73 isoforms in these tumours. This study highlights important species-specific differences in the transcriptional regulation of TP53. Considering the similarities of TP53 regulation between pig and human, these observations provide useful pointers for further investigation into isoform function including the novel circTP53 in both the pig model and human patients.

Background/aim: Surgical resection for soft tissue sarcomas (STSs) is the gold standard for a curative oncologic therapy in combination with neoadjuvant or adjuvant radiation therapy (NRT/ART). The aim of this study was to determine prognostic factors influencing the survival of patients with STS undergoing NRT or ART considering various parameters in a retrospective, single-centre analysis over 15 years., Patients and Methods: We included 119 patients (male 59) and the median follow-up period was 69 months (4-197). The patients received NRT (n=64) or ART (n=55). We recorded the histopathologic subtype of STS, tumour grade, localization, tumour margins, complications, survival, local recurrence, and metastases. Survival analysis was performed using the Kaplan-Meier method., Results: The overall survival rate was 68.9% at 5 years. The localization (epifascial/subfascial), resection margin and type of radiation therapy (NRT/ART) had no significant impact on survival. Tumour grade, tumour size, local recurrence and metastases were significantly correlated with patient survival (p<0.05). Local recurrence was significantly higher in patients with ART (p=0.044)., Conclusion: Tumour grade and tumour size were independently associated with disease-specific survival, and patients with local recurrence and metastases had lower survival rates., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Quantitative magnetic resonance (MR) imaging techniques are established for evaluation of cartilage composition and trabecular bone microstructure at the knee. It remains unclear whether quantitative MR parameters predict the midterm morphological outcome after matrix-associated chondrocyte implantation (MACI) with autologous bone grafting (ABG)., Purpose: To assess longitudinal changes and associations of the biochemical composition of cartilage repair tissue, the subchondral bone architecture, and morphological knee joint abnormalities on 3-T MR imaging after MACI with ABG at the knee., Study Design: Case series; Level of evidence, 4., Methods: Knees of 18 patients (28.7 ± 8.4 years [mean ± SD]; 5 women) were examined preoperatively and 3, 6, 12, and 24 months after MACI and ABG using 3-T MR imaging. Cartilage composition was assessed using T 2 relaxation time measurements. Subchondral bone microstructure was quantified using a 3-dimensional phase-cycled balanced steady-state free precision sequence. Trabecular bone parameters were calculated using a dual threshold algorithm (apparent bone fraction, apparent trabecular number, and apparent trabecular separation). Morphological abnormalities were assessed using the MOCART (magnetic resonace observation of cartilage repair tissue) score, the WORMS (Whole-Organ Magnetic Resonance Imaging Score), and the CROAKS (Cartilage Repair Osteoarthritis Knee Score). Clinical symptoms were assessed using the Tegner activity and Lysholm knee scores. Statistical analyses were performed by using multiple linear regression analysis., Results: Total WORMS ( P = .02) and MOCART ( P = .001) scores significantly improved over 24 months after MACI. Clinical symptoms were significantly associated with the presence of bone marrow edema pattern abnormalities 24 months after surgery ( P = .035). Overall there was a good to excellent radiological outcome found after 24 months (MOCART score, 88.8 ± 10.1). Cartilage repair T 2 values significantly decreased between 12 and 24 months after MACI ( P = .009). Lower global T 2 values after 3 months were significantly associated with better MOCART scores after 24 months ( P = .04). Moreover, trabecular bone parameters after 3 months were significantly associated with the total WORMS after 24 months (apparent bone fraction, P = .048; apparent trabecular number, P = .013; apparent trabecular separation, P = .013)., Conclusion: After MACI with ABG, early postoperative quantitative assessment of biochemical composition of cartilage and microstructure of subchondral bone may predict the outcome after 24 months. The perioperative global joint cartilage matrix quality is essential for proper proliferation of the repair tissue, reflected by MOCART scores. The subchondral bone quality of the ABG site is essential for proper maturation of the cartilage repair tissue, reflected by cartilage T 2 values.

Background: Peri-prosthetic joint infection (PJI) is a major complication of knee arthroplasty that can cause long-term disability. In addition to its physical impact, there is a clear psychological burden that has not been measured yet. We hypothesized that the psychosocial burden of PJI can be assessed quantitatively using standardized questionnaires and may be correlated with treatment stage. Methods: Thirty-one patients were enrolled in this longitudinal prospective cohort study from August 2015 to November 2016. Participants had clinically established knee PJI after primary total knee replacement in osteoarthritis according to the Musculoskeletal Infection Society criteria and underwent a standardized two-stage protocol. After explantation of the prosthesis and implantation of a polymethylmethacrylate knee spacer, patients were treated with organism-specific intravenous antibiotics for two weeks, followed by oral antibiotics for four weeks; and then reimplantation was performed in all cases. Psychometrically validated standardized questionnaires were used to measure psychosocial stress via self-assessment at four time points: (1) Before explantation of the prosthesis; (2) after explantation; (3) after the antibiotic treatment before reimplantation; and (4) three months after reimplantation (follow-up). The Patient Health Questionnaire (PHQ)-4, Short Form (SF)-12 (including PSK and KSK), Questions about Life Satisfaction (FLZ M ) and Fear of Progression (PA-F-KF) (titles and abbreviations in German) scores were interpreted according to cut-off values for depression, fear of progression, anxiety, and quality of life. Results: Eighteen patients (58.1%) showed a PHQ-4 score above the cut-off value for depression at least once, with the highest score before reimplantation (time point 3). On the SF-12, the mean subtest mental scale (PSK) score was 42.6 (± 14.5), and the mean subtest physical scale (KSK) score was 26.9 (± 7.5) over the four time points, which was significantly lower than that of the general German population (PSK 53.1, KSK 44.0; p < 0.05). The SF-12 scores did not change significantly over time. On the FLZ, health was least satisfactory, followed by recreational activities and work. On the PA-F-KF, patients had the greatest fear of being dependent on outside help, drastic medical interventions, and infection progression. The mean PA-F-KF value was 31.24 (± 9.60; values ≥34 are regarded as critical). Conclusion: Peri-prosthetic joint infection is a measurable, relevant psychosocial stressor for patients. Their quality of life and fear of the disease progressing are comparable to those of oncology patients. Routine screening should be conducted to identify affected patients early for appropriate treatment, improving long-term outcomes. Orthopaedic surgeons who treat patients with PJI should initiate by psychologists as well in order to maintain the patient's long-term quality of life.

Background/aim: Myxofibrosarcoma (MFS) is characterized by an infiltrative growth pattern. This study aimed to determine the correlation between overall survival (OS) and morphological features of MFS as well as examine the reproducibility of these findings on preoperative magnetic resonance imaging (MRI)., Patients and Methods: Fifty-eight MFS patients underwent preoperative MR imaging with the following features analysed: i) tumour size, ii) localization, iii) margins, iv) morphology, v) signal characteristics, vi) contrast enhancement, vii) presence and extent of perilesional oedema, and viii) presence of the tail sign., Results: Only circumscribed perilesional oedema was associated with a significantly better survival compared to diffuse oedema (p=0.010), which was found in the majority of cases. The tail sign was found in less than 50% of the cases. Cohen's kappa coefficients confirmed a relatively high interrater variability., Conclusion: Perilesional diffuse oedema on MR imaging of MFS is significantly correlated with a poor overall survival. The interrater variability in interpretation of MR examinations varies from slight to substantial agreement. Preoperative MR imaging with detailed planning of the resection seem to be a logical approach to achieve negative resection margins and recurrence-free survival., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Despite increasing numbers of primary hip arthroplasties performed through the direct anterior approach (DAA), there is a lack of literature on DAA revision arthroplasty. The present study was performed in order to evaluate outcomes and revision rates after revision through the DAA using an asymmetric acetabular component with optional intra- and extramedullary fixation. In a retrospective cohort study, we analyzed prospectively collected data of 57 patients (61 hips, 43 female, 18 male) who underwent aseptic acetabular component revision through the DAA with the abovementioned implant system between January 2015 and December 2017. The mean follow-up was 40 months (12-56). Survival rates were estimated using the Kaplan-Meier method. All complications were documented and functional outcomes were assessed pre- and postoperatively. Kaplan-Meier analysis revealed an estimated five-year implant survival of 97% (confidence interval CI 87-99%). The estimated five-year survival with revision for any cause was 93% (CI 83-98%). The overall revision rate was 6.6% (n = 4). Two patients had to undergo revision due to periprosthetic infection (3.3%). In one patient, the acetabular component was revised due to aseptic loosening four months postoperatively. Another patient suffered from postoperative iliopsoas impingement and was treated successfully by arthroscopic iliopsoas tenotomy. Two (3.3%) of the revised hips dislocated postoperatively. The mean Harris Hip Score improved from 35 (2-66) preoperatively to 86 (38-100) postoperatively ( p < 0.001). The hip joint's anatomical center of rotation was restored at a high degree of accuracy. Our findings demonstrate that acetabular revision arthroplasty through the DAA using an asymmetric acetabular component with optional intra- and extramedullary fixation is safe and practicable, resulting in good radiographic and clinical midterm results.

Background: Safe diagnosis of periprosthetic joint infection (PJI) is of utmost importance for successful exchange arthroplasty. However, current diagnostic tools show insufficient accuracy in the clinically common and challenging chronic low-grade infections. To close this diagnostic gap, reliable (bio)markers display the most promising candidates. Antimicrobial peptides (AMPs) are part of the innate immune response towards microbial growth. Recently we could show significant intraarticular levels of human cathelicidin LL-37 and β-defensin-3 (HBD-3) with high diagnostic accuracy in PJI synovial fluid. Consequently, these promising biomarkers were evaluated in PJI synovial membrane and synoviocytes, which may significantly facilitate histological diagnosis of PJI to improve outcome of septic joint replacement., Methods: In this prospective single-center controlled clinical study (diagnostic level II), consecutive patients with total hip (THR) and knee (TKR) replacements were included undergoing primary arthroplasty (n = 8), surgical revision due to aseptic loosening (n = 9) and septic arthroplasty with coagulase-negative staphylococci (n = 8) according to the criteria of the Musculoskeletal Infection Society (MSIS). Semiquantitative immunohistochemical (IHC) analysis of LL-37, HBD-3 and HBD-2 in synovial membrane and isolated synoviocytes based on Total Allred Score (TS) and Immunoreactive Remmele and Stegner score (IRS) was performed. For statistical analysis, SPSS 26.0/R3.6.3 (p < 0.05) was used., Results: The AMPs LL-37 and HBD-3 were significantly elevated (up to 20×) in synovial membranes from PJI compared to aseptic loosening or primary arthroplasty. The area under the curve (AUC) in a receiver operating characteristic curve analysis was equal to 1.0 for both scores revealing excellent diagnostic accuracy. Isolated synoviocytes as cellular AMP source showed comparable results with a significant LL-37/HBD-3-increase up to 3 × in PJI. In contrast, local HBD-2 levels were negligible (p > 0.23) upon PJI with a lower diagnostic accuracy (AUC = 0.65) in analogy to our previous findings with synovial fluid., Conclusions: Our results implicate AMPs as promising and specific biomarkers for the histological diagnosis of PJI.

Gluteal insufficiency or hip abductor mechanism deficiency mainly following (revision) total hip replacement is associated with highly painful complaints and severe suffering of patients. It represents a great diagnostic and therapeutic challenge. Differentiated conservative treatment pathways, open surgical and endoscopic anatomic repair techniques with intact gluteal musculature and muscle transfer are available as salvage procedures for chronic not anatomically reconstructable mass ruptures. A stepwise diagnostic and therapeutic approach is required for restoration of the quality of life and painless or almost painless mobility of affected patients in occupation and daily life.

Background: For focal cartilage defects, biological repair might be ineffective in patients over 45 years. A focal metallic implant (FMI) (Hemi-CAP Arthrosurface Inc., Franklin, MA, USA) was designed to reduce symptoms. The aim of this study was to evaluate the effects of a FMI on the opposing tibial cartilage in a biomechanical set-up. It is hypothesized that a FMI would not damage the opposing cartilage under physiological loading conditions., Methods: An abrasion machine was used to test the effects of cyclic loading on osteochondral plugs. The machine applied a compressive load of 33 N and sheared the samples 10 mm in the anteroposterior direction by 1 Hz. Tibial osteochondral plugs from porcine knees were placed in opposition to a FMI and cycled for 1 or 6 h. After testing each plug was fixed, stained and evaluated for cartilage damage., Results: After 1 h of loading (n = 6), none of the osteochondral plugs showed histologic signs of degradation. After 6 h of loading (n = 6) three samples had histologic signs of injury in the tangential zone (grade 1) and one had signs of injury in the transitional and deep zones (grade 2). Exploration for 6 h resulted in significant more cartilage damage compared to the shorter exploration time (p = 0.06). However, no significant difference between saline and hyaluronic acid was evident (p = 0.55)., Conclusion: Under physiologic loading conditions, contact with a FMI leads to cartilage damage in the opposing articular cartilage in six hours. In clinical practice, a thorough analysis of pre-existing defects on the opposing cartilage is recommended when FMI is considered.

Background: Aim of the present study is the evaluation of ultrasound as a physical method for virus inactivation in human plasma products prior to transfusion. Our study is focused on achieving a high level of virus inactivation simultaneously leaving blood products unaltered, measured by the level of degradation of coagulation factors, especially in third world countries where virus contamination of blood products poses a major problem. Virus inactivation plays an important role, especially in the light of newly discovered or unknown viruses, which cannot be safely excluded via prior testing., Methods: Taking into account the necessary protection of the relevant coagulation activity for plasma, the basis for a sterile virus inactivation under shielding gas insufflation was developed for future practical use. Influence of frequency and power density in the range of soft and hard cavitation on the inactivation of transfusion-relevant model viruses for Hepatitis-(BVDV = bovine diarrhea virus), for Herpes-(SFV = Semliki Forest virus, PRV = pseudorabies virus) and Parvovirus B19 (PPV = porcine parvovirus) were examined. Coagulation activity was examined via standard time parameters to minimize reduction of functionality of coagulation proteins. A fragmentation of coagulation proteins via ultrasound was ruled out via gel electrophoresis. The resulting virus titer was examined using end point titration., Results: Through CO 2 shielding gas insufflation-to avoid radical emergence effects-the coagulation activity was less affected and the time window for virus inactivation substantially widened. In case of the non-lipidated model virus (AdV-luc = luciferase expressing adenoviral vector), the complete destruction of the virus capsid through hard cavitation was proven via scanning electron microscopy (SEM). This can be traced back to microjets and shockwaves occurring in hard cavitation. The degree of inactivation seems to depend on size and compactness of the type of viruses. Using our pre-tested and subsequently chosen process parameters with the exception of the small PPV, all model viruses were successfully inactivated and reduced by up to log 3 factor. For a broad clinical usage, protection of the coagulation activities may require further optimization., Conclusions: Building upon the information gained, an optimum inactivation can be reached via raising of power density up to 1200 W and simultaneous lowering of frequency down to 27 kHz. In addition, the combination of the two physical methods UV treatment and ultrasound may yield optimum results without the need of substance removal after the procedure.

Purpose: Arthroscopic partial meniscectomy of medial meniscus tears and varus alignment are considered independent risk factors for increased medial compartment load, thus contributing to the development of medial osteoarthritis. The purpose of this biomechanical study was to investigate the effect of lower limb alignment on contact pressure and contact area in the knee joint following sequential medial meniscus resection. It was hypothesized that a meniscal resection of 50% would lead to a significant overload of the medial compartment in varus alignment., Methods: Eight fresh-frozen human cadaveric knees were axially loaded with a 750 N compressive force in full extension with the mechanical axis rotated to intersect the tibia plateau at 30%, 40%, 50%, 60% and 70% of its width. Tibiofemoral mean contact pressure (MCP), peak contact pressure (PCP), and contact area (CA) of the medial and lateral compartment were measured separately using pressure-sensitive films (K-Scan 4000, Tekscan) in four different meniscal conditions, respectively, intact, 50% resection, 75% resection, and total meniscectomy., Results: Medial MCP was significantly increased when comparing the intact meniscus to each meniscal resection in all tested alignments (p < 0.05). Following meniscal resection of 50%, MCP was significantly higher with greater varus alignment compared to valgus alignment (p < 0.05). Similarly, medial PCP was higher at varus alignment compared to valgus alignment (p < 0.05). Further resection to 75% and 100% of the meniscus resulted in a significantly higher medial PCP at 30% of tibia plateau width compared to all other alignments (p < 0.05). Medial CA of the intact meniscus decreased significantly after 50%, 75% and 100% meniscal resection in all alignments (p < 0.05). Lateral joint pressure was not significantly increased by greater valgus alignment., Conclusion: Lower limb alignment and the extent of medial meniscal resection significantly affect tibiofemoral contact pressure. Combined varus alignment and medial meniscal resection increased MCP and PCP within the medial compartment, whereas valgus alignment prevented medial overload. As a clinical consequence, lower limb alignment should be considered in the treatment of patients undergoing arthroscopic partial meniscectomy with concomitant varus alignment. In patients presenting with ongoing medial joint tenderness and effusion, realignment osteotomy can be a surgical technique to unload the medial compartment.

Purpose: Assessment of medial meniscus extrusion (MME) has become increasingly popular in clinical practice to evaluate the dynamic meniscus function and diagnose meniscus pathologies. The purpose of this biomechanical study was to investigate the correlation between MME and the changes in joint contact pressure in varus and valgus alignment. It was hypothesized that varus alignment would result in significantly higher MME along with a higher joint contact pressure in the medial compartment., Methods: Eight fresh-frozen human cadaveric knees were axially loaded, with a 750 N compressive load, in full extension with the mechanical axis shifted to intersect the tibial plateau at 30% and 40% (varus), 50% (neutral), 60% and 70% (valgus) of its width (TPW). Tibiofemoral peak contact pressure (PCP), mean contact pressure (MCP) and contact area (CA) were determined using pressure-sensitive films. MME was obtained via ultrasound at maximum load., Results: MME was significantly increased from valgus (1.32 ± 0.22 mm) to varus alignment (3.16 ± 0.24 mm; p < 0.001). Peak contact pressure at 30% TPW varus alignment was significantly higher compared to 60% TPW valgus (p = 0.018) and 70% TPW valgus (p < 0.01). MME significantly correlated with PCP (r = 0.56; p < 0.001) and MCP (r = 0.47, p < 0.01) but not with CA (r = 0.23; n.s.)., Conclusion: MME was significantly increased in varus alignment, compared to neutral or valgus alignment, with an intact medial meniscus. It was also significantly correlated with PCP and MCP within the medial compartment. However, valgus malalignment and neutral axis resulted in reduced MME and contact pressure. Lower limb alignment must be taken into account while assessing MME in clinical practice., Level of Evidence: Controlled laboratory study.

Purpose: Displaced tibial posterior cruciate ligament (PCL) avulsion fractures require surgical fixation in order to provide an adequate bone healing and to avoid a loss of posterior stability. The purpose of this study was to compare the biomechanical properties of a recently established modified suture bridge technique to a well-established transtibial pullout technique. It was hypothesized that the suture bridge technique shows lower elongation and higher load to failure force compared to a transtibial pullout fixation., Methods: Twelve fresh-frozen human cadaveric knees were biomechanically tested using an uniaxial hydrodynamic material testing system. A standardized bony avulsion fracture of the tibial PCL insertion was generated. Two different techniques were used for fixation: (A) suture bridge configuration and (B) transtibial pullout fixation. In 90° of flexion elongation, initial stiffness and failure load were determined., Results: The suture-bridge technique resulted in a significant lower elongation (4.5 ± 2.1 mm) than transtibial pullout technique (12.4 ± 3.0 mm, p < 0.001). The initial stiffness at the beginning of cyclic loading was 46.9 ± 3.9 N/mm in group A und 40.8 ± 9.0 N/mm in group B (p = 0.194). Load to failure testing exhibited 286.8 ± 88.3 N in group A and 234.3 ± 96.8 N in group B (p = 0.377)., Conclusion: The suture bridge technique provides a significant lower construct elongation during cyclic loading. But postoperative rehabilitation must respect the low construct strength of both techniques because both fixation techniques did not show a sufficient fixation strength to allow for a more aggressive rehabilitation.

Background: Beside botulinum-toxin injections and hyaluronic acid fillers, thread lifts have established themselves as the third column of minimally invasive facial rejuvenation. Most commonly, barbed threads for this approach are made out of polydioxanone, a material known for decades from application in resorbable sutures. The clinical efficacy and the putative material safety of polydioxanone have fueled the popularity of thread lifts., Methods: The present study highlights significant variation among six commercially available threads in microstructure, tensile strength, elasticity, anchoring capacity in human tissue, and biocompatibility., Results: Despite their license to be marketed and sold in the European Union, some products performed significantly worse than others on material testing, and even displayed cytotoxic characteristics., Conclusion: The results of this study are highly relevant for clinicians and may be linked to various typical side effects of polydioxanone threads for facial rejuvenation.