Search

The cricothyroid joint (CTJ) plays a key role in pitch adjustment of the human voice. It allows an external elongation of the vocal fold performed by the cricothyroid muscle with a consecutive stretching and increasing of tension. Phonosurgical methods such as cricothyroid approximation need sophisticated investigations on anatomical and functional principles because of the low satisfaction rates. Fifty cadaveric specimens were analyzed to reveal the morphological and functional anatomy of the CTJ focusing on possible gliding movements in a horizontal and vertical direction. The cartilaginous surfaces of the CTJ were categorized according to Maue and Dickson into three different types (type A: well-defined facet; type B: no definable facet; type C: flat cartilage surface or protuberance) and functional correlations examined. Side different statements and intraindividual differences between male and female specimens were included. Besides from rotational movements, the CTJ allowed horizontal and vertical gliding movements depending on the different types of the cartilaginous surfaces. Especially the difference concerning mobility between type A and the others was highly significant (P<0.001). Two thirds of our specimens showed a similar type in both CTJs, whereas in one third it was asymmetric. In comparison to the possible change of distances between horizontal gliding movements and rotation, rotation caused significant elongation of the vocal folds, which should be proposed in phonosurgical methods for cricothyroid approximation. [ABSTRACT FROM AUTHOR]

STUDY DESIGN.: Case report and review of the literature. OBJECTIVE.: We report a case of Grisel's syndrom with a delayed diagnosis. The patient's first presentation in our pediatric orthopedics department was 2 month after surgery (cochlea implantation) with a persistent torticollis. Radiographs revealed a subluxated atlantoaxial joint. We treated our patient with manual repositioning and calculated antibiotics, which lead to a restitutio ad integrum within a short time. SUMMARY OF BACKGROUND DATA.: Grisel's syndrome is synonymous with rare nontraumatic, rotational subluxation of the atlantoaxial joint (C1-C2). All formerly reported cases showed a clear association to infection or were related to head and neck surgery. Still, there is a lack of understanding about pathogenetic features and causative agents. In 1977 Fielding proposed a classification of the atlantoaxial subluxation and stage-related therapy was recommended. METHODS.: Our patient was a 11-year-old girl with a torticollis after insertion of a cochlea implant. After surgery, physiotherapy was performed because of her wryneck. As the symptoms did not improve, she was presented in our clinic. Our radiographs revealed a subluxated atlantoaxial joint. RESULTS.: In general anesthesia we performed a manual repositioning and she was temporarily immobilized with a cervical collar for 2 weeks. In addition, we administered calculated antibiotics, although CRP and leukocytes were not elevated. The follow up showed a good repositioning within a short time. CONCLUSION.: At least in this case, our treatment led to shorter recovery and avoidance of halo fixation. Our new therapeutic approach to patients with Grisel's syndrome might lead to a shorter recovery. [ABSTRACT FROM AUTHOR]

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.)

Background: In revision total knee arthroplasty, zonal fixation methods with a combination of augments, press-fit stems, and sleeves are popular. We hypothesized that high distal femoral augmentation with diaphyseal press-fit stems leads to an increased rate of early aseptic loosening and that femoral metaphyseal sleeves improve implant survival. Therefore, we retrospectively investigated implant survival in relation to augment heights and sleeves., Methods: A total of 136 patients with mean clinical follow-up of 50 months (range, 28-85) who underwent modular total knee arthroplasty and revision total knee arthroplasty with semiconstrained implants between January 2012 and July 2018 were retrospectively evaluated. Implant survival with 4, 8, and 12 mm distal femoral augments was compared to no distal augmentation. Subsequently, a subgroup analysis was performed for femoral sleeve implantation., Results: We observed an implant survival rate of 97.0%, 87.5%, and 69.2% for 4, 8, and 12 mm distal femoral augmentation, respectively (P = .73; P = .19; P = .008). The implant survival rate with femoral sleeves was 95.8% for the 8 mm augments and 85.7% for the 12 mm augments (P = .42; P = .96). Without femoral sleeves, the implant survival rate was 78.3% with the 8 mm augments and 50.0% with the 12 mm augments (P = .02; P < .001)., Conclusion: Higher rates of aseptic femoral loosening were identified for distal femoral augmentation of 8 mm or more without metaphyseal sleeve fixation in semiconstrained implants. Thus, in cases with femoral metaphyseal bone damage requiring high distal femoral augmentation, metaphyseal sleeves should be used to avoid early aseptic femoral loosening., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

In winter sports, skiers, snowboarders and ice hockey players have the highest risk of traumatic brain injuries (TBI). In skiing/snowboarding severe TBIs are of concern; in ice hockey, repetitive minor TBIs are frequent. The main causes of TBI in recreational skiing are collisions with trees; in professionals falls due to technical or tactical mistakes are the main causes. In ice hockey 10-15% of all injuries are due to a sports-related concussion (SRC), mostly caused by player-opponent contact. The pathomechanism in TBI is a combination of rotational and linear acceleration during head impact, which causes a diffuse axonal injury. Long-term complications such as neurodegenerative diseases and functional deficits are of relevance. Prevention by wearing helmets is effective, but less effective in TBI/SRC than in focal injuries., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: The aim of this study was to analyze incidences and sport-specific injury patterns among users of a bodyweight-based training method instructed by a smartphone app (Freeletics Bodyweight App)., Methods: An online questionnaire based on current validated epidemiological observation methods was designed using the statistic website Surveymonkey. Subscribers of the Freeletics Bodyweight App were contacted via an online link. Injury incidence, defined as an event leading to a training pause of at least 1 day, was recorded. The type of injury was reported and classified. Furthermore, all participants were asked whether they recognized any positive or negative effects on their subjective health status. The collected data were analyzed using Surveymonkey statistic services., Results: A total of 4365 Freeletics users responded to the questionnaire, 3668 completed forms were subject of further investigation. The injury period prevalence reported by users of the Freeletics App was 24% in men and 21% in women. The most frequently reported site of injury was the shoulder (29%) and the knee joint (28%), with strains (28.5%) and other muscle injuries (14.4%) being the most frequently reported types of injuries. An injury incidence rate of 4.57 per 1000 h was calculated, with injuries occurring less frequently in experienced users. Most participants reported a distinct positive effect of the app-based training on their health status., Conclusion: In comparison to other sports activities app-based bodyweight training is associated with a comparably low injury period prevalence. The vast majority of injuries were reported to have resolved within one week., (© 2022. The Author(s).)

Introduction: High tibial osteotomy (HTO) is a valid and joint preserving surgical technique to treat medial degenerative osteoarthritis (OA) in young and active patients. A recent study shows that patients' expectations of osteotomy around the knee are high, but OA progression and potential conversion to a total knee arthroplasty (TKA) were underestimated. The aim of this study was to investigate surgeons' expectations of HTO and to compare the results to the patients' expectations and actual outcomes reported in the literature., Methods: 461 surgeons were questioned online using the 'Hospital for Special Surgery Knee Surgery Expectations Survey (HFSS-KSES)' and a ten-item non-validated questionnaire to investigate the expectations of HTO. Two subgroups were formed to investigate differences regarding the surgeons' experience. Statistical analysis was performed using IBM SPSS Statistics., Results: Surgeons' expectations of HTO were rated between very and little important with pain reduction being the most important item on the HFSS-KSES. Furthermore, 'improving the ability to walk', 'to perform daily activities', 'having confidence in the knee', and 'avoiding future degeneration' were rated of high importance. An important difference regarding the experience was the lower expectations on delay/prevention of TKA of less-experienced surgeons., Conclusion: Surgeons' expectations of HTO are high but nevertheless different to the patients' expectations reported in the literature. Also, expectations for the delay/prevention of TKA differed regarding the experience of surgeons. While pain reduction represents one of the most important items for surgeons and patients, the expected outcome regarding the delay/prevention of a TKA and returning to sports differs to the patients' expectations and to the actual outcome reported in the literature. This should be considered when performing the preoperative informed consent., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The diagnosis and treatment of periprosthetic joint infection (PJI) currently relies on cultures, which are time-consuming and often fail. Multiplex PCR assays promise reliable and prompt results, but have been heterogeneously evaluated. In this study, we analyse multiplex PCR in pathogen identification using only tissue biopsies. 42 patients after revision arthroplasty of the hip or knee were evaluated using multiplex PCR to identify microorganisms. The patients were classified according to the diagnostic criteria published by Zimmerli et al. and the results were compared to the respective microbiological cultures. PJI was detected in 15 patients and 27 revisions were aseptic. The multiplex PCR of tissue biopsies had a sensitivity of 0.3 (95% CI 0.12-0.62), a specificity of 1.0 (0.87-1.0), a positive predictive value of 1.0 (0.48-1.0) and a negative predictive value of 0.73 (0.56-0.86). The diagnostic accuracy of multiplex PCR on tissue biopsy samples is low in comparison to routine microbiological cultures. The evaluation of tissue biopsies using multiplex PCR was prone to false negative results. However, multiplex PCR assays have the advantage of rapid pathogen identification. We therefore recommend further investigation of multiplex PCR in the setting of suspected PJI with a careful choice of specimens., (© 2021. The Author(s).)

Background: There is no universally accepted treatment standard for idiopathic toe walking patients (ITW) in the current literature. None of the established methods provide homogenous satisfying results. In our department we treat ITW patients with lower leg orthoses with a circular foot unit for a total of 16 weeks. In this study we reviewed our database to evaluate the success of our treatment protocol for a 24 months follow up period., Results: Twenty-two patients were included in this study. Age at the beginning of treatment was 7.0 years +/- 2.9 (range 2.5-13.1). Percentage of ITW at the beginning of treatment according to the perception of the parents was 89% +/- 22.2 (range 50-100). Immediately after the treatment with our device, percentage of ITW dropped to 11% +/- 13.2 (range 0-50). After 12 months, 73% of the patients (16/22) walked completely normal or showed ITW less than 10% of the day. After 24 months, 64% of the patients kept a normal gait (14/22)., Conclusion: This study provides evidence that the treatment of idiopathic toe walking with lower leg orthoses with a circular foot unit results in satisfying long-term results in two thirds of the patients.

As most chemotherapeutic drugs are ineffective in the treatment of chondrosarcoma, we studied the expression pattern and function of SOX9, the master transcription factor for chondrogenesis, in chondrosarcoma, to understand the basic molecular principles needed for engineering new targeted therapies. Our study shows an increase in SOX9 expression in chondrosarcoma compared to normal cartilage, but a decrease when the tumors are finally defined as dedifferentiated chondrosarcoma (DDCS). In DDCS, SOX9 is almost completely absent in the non-chondroid, dedifferentiated compartments. CRISPR/Cas9-mediated knockout of SOX9 in a human chondrosarcoma cell line (HTB94) results in reduced proliferation, clonogenicity and migration, accompanied by an inability to activate MMP13. In contrast, adhesion, apoptosis and polyploidy formation are favored after SOX9 deletion, probably involving BCL2 and survivin. The siRNA-mediated SOX9 knockdown partially confirmed these results, suggesting the need for a certain SOX9 threshold for particular cancer-related events. To increase the efficacy of chondrosarcoma therapies, potential therapeutic approaches were analyzed in SOX9 knockout cells. Here, we found an increased impact of doxorubicin, but a reduced sensitivity for oncolytic virus treatment. Our observations present novel insight into the role of SOX9 in chondrosarcoma biology and could thereby help to overcome the obstacle of drug resistance and limited therapy options.

Purpose: To evaluate imaging characteristics obtained from magnetic resonance imaging (MRI) with metal artifact reduction (MAR) to differentiate between periprosthetic joint infection (PJI), aseptic loosening and cases without these pathologies after total hip arthroplasty (THA)., Methods: Patients with THA (n = 41; mean age 66.4 ± 9.6 years; 25 women) undergoing 1.5 T MRI with high-bandwidth sequences and view angle tilting followed by revision surgery within 3 months were identified retrospectively. Imaging findings at the metal-bone interface, in the surrounding bone, the soft tissues and lymphadenopathy were assessed by three radiologists in a standardized fashion. Based on clinical and intraoperative findings, patients were categorized in groups with PJI (n = 15), aseptic loosening (n = 15) or without these pathologies (n = 11). Imaging findings were assessed in crosstabs, receiver-operating characteristics and classification and regression trees., Results: Findings at the acetabular cup were specific for the presence of either PJI or aseptic loosening (specificity>0.765 for all), while findings at the stem were sensitive (sensitivity>0.824 for all except periostitis). To differentiate PJI versus aseptic loosening, soft tissue edema (sensitivity, 0.867/specificity>0.733), abnormalities at both, acetabular and femoral components (0.667/0.933-1.000) and enlarged lymph nodes (0.800/0.867) were accurate., Conclusion: Standardized assessment of MR imaging findings in THA patients facilitated the differentiation of PJI and aseptic loosening. This information can be helpful for therapy planning., (Copyright © 2020 Elsevier B.V. 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: A major obstacle for the treatment of prosthetic joint infection (PJI) is the identification of the underlying causative organism. While the diagnostic criteria ruling PJI in or out have become ever more accurate, the detection of the causative pathogen(s) still relies mostly on conventional and time-consuming microbial culture. The aim of this study was to evaluate the diagnostic potential of a second-generation multiplex PCR assay (Unyvero ITI G2, Curetis AG, Holzgerlingen, Germany) used on synovial fluid specimens. Our hypothesis was that the method would yield a higher diagnostic accuracy in the pre-operative workup than synovial fluid culture. Thus, a more precise classification of septic and aseptic prosthesis failure could be achieved before revision surgery., Methods: Prospectively collected frozen joint fluid specimens from 26 patients undergoing arthroplasty revision surgery of the hip or knee were tested as per the manufacturer's protocol. Sensitivities, specificities, positive and negative predictive values as well as positive and negative likelihood ratios with corresponding confidence intervals were estimated using the statistical software R. A combination of the serum C-reactive protein (CRP) level, leukocyte count, erythrocyte sedimentation rate, joint fluid culture, tissue biopsy culture, and tissue biopsy histology served as the gold standard., Results: Of the 26 patients included in the study, 15 were infected and 11 were aseptic. Conventional joint fluid culture showed a sensitivity of 0.67 and a specificity of 0.91. Joint fluid multiplex PCR yielded a sensitivity of 0.8 and a specificity of 1.0., Conclusions: Using the second-generation Unyvero ITI cartridge on joint fluid aspirate for the detection of prosthetic joint infection, we were able to achieve a higher diagnostic accuracy than with conventional culture. We conclude that to improve pathogen detection before revision surgery, this method represents a valuable and practicable tool.

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.

Introduction: Targeting the cell cycle machinery represents a rational therapeutic approach in myelodysplastic syndromes (MDS) and secondary acute myeloid leukemia (sAML). Despite substantial response rates, clinical use of the PLK inhibitor volasertib has been hampered by elevated side effects such as neutropenia and infections., Objectives: The primary objective was to analyse whether a reduced dose of volasertib was able to limit toxic effects on the healthy haematopoiesis while retaining its therapeutic effect., Methods: Bone marrow mononuclear cells (BMMNCs) of patients with MDS/sAML (n = 73) and healthy controls (n = 28) were treated with volasertib (1 μM to 1 nM) or vehicle control. Short-term viability analysis was performed by flow cytometry after 72 hours. For long-term viability analysis, colony-forming capacity was assessed after 14 days. Protein expression of RIPK3 and MCL-1 was quantified via flow cytometry., Results: Reduced dose levels of volasertib retained high cell death-inducing efficacy in primary human stem and progenitor cells of MDS/sAML patients without affecting healthy haematopoiesis in vitro. Interestingly, volasertib reduced colony-forming capacity and cell survival independent of clinical stage or mutational status., Conclusions: Volasertib offers a promising therapeutic approach in patients with adverse prognostic profile. RIPK3 and MCL-1 might be potential biomarkers for sensitivity to volasertib treatment., (© 2019 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Patients with Myelodysplastic Syndromes (MDS) and secondary Acute Myeloid Leukemia (sAML) have a very poor prognosis after failure of hypomethylating agents (HMA). Stem cell transplantation is the only effective salvage therapy, for which only a limited number of patients are eligible due to age and comorbidity. Combination therapy of venetoclax and azacitidine (5-AZA) seems to be a promising approach in myeloid malignancies, but data from patients with HMA failure are lacking. Furthermore, a considerable concern of combination regimens in elderly AML and MDS patients is the toxicity on the remaining healthy hematopoiesis. Here, we report in vitro data showing the impact of venetoclax and 5-AZA, alone or in combination, in a larger cohort of MDS/sAML patients (n = 21), even after HMA failure (n = 13). We especially focused on the effects on healthy hematopoiesis and the impact on colony forming capacity as a parameter for long-term effects. To the best of our knowledge, we show for the first time that venetoclax in combination with capped dose of 5-AZA targets cell malignancies, while sparing healthy hematopoiesis., Competing Interests: The authors declare that they have no competing interests.

The quest for predictive tumor markers for osteosarcoma (OS) has not well progressed over the last two decades due to a lack of preclinical models. The aim of this study was to investigate if microenvironmental modifications in an original humanized in vivo model alter the expression of OS tumor markers. Human bone micro-chips and bone marrow, harvested during hip arthroplasty, were implanted at the flanks of NOD/scid mice. We administered recombinant human bone morphogenetic protein 7 (rhBMP-7) in human bone micro-chips/bone marrow group I in order to modulate bone matrix and bone marrow humanization. Ten weeks post-implantation, human Luc-SAOS-2 OS cells were injected into the humanized tissue-engineered bone organs (hTEBOs). Tumors were harvested 5 weeks post-implantation to determine the expression of the previously described OS markers ezrin, periostin, VEGF, HIF1α and HIF2α. Representation of these proteins was analyzed in two different OS patient cohorts. Ezrin was downregulated in OS in hTEBOs with rhBMP-7, whereas HIF2α was significantly upregulated in comparison to hTEBOs without rhBMP-7. The expression of periostin, VEGF and HIF1α did not differ significantly between both groups. HIF2α was consistently present in OS patients and dependent on tumor site and clinical stage. OS patients post-chemotherapy had suppressed levels of HIF2α. In conclusion, we demonstrated the overall expression of OS-related factors in a preclinical model, which is based on a humanized bone organ. Our preclinical research results and analysis of two comprehensive patient cohorts imply that HIF2α is a potential prognostic marker and/or therapeutic target. STATEMENT OF SIGNIFICANCE: This study demonstrates the clinical relevance of the humanized organ bone microenvironment in osteosarcoma research and validates the expression of tumor markers, especially HIF2α. The convergence of clinically proven bone engineering concepts for the development of humanized mice models is a new starting point for investigations of OS-related marker expression. The validation and first data set in such a model let one conclude that further clinical studies on the role of HIF2α as a prognostic marker and its potential as therapeutic target is a condition sine qua non., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

In addition to their outstanding significance in the field of tumor orthopaedics, megaprostheses are becoming increasingly important for revision arthroplasty. Despite their wide application, the reported complication and failure rates remain high. The analysis of failure mechanisms roughly allows a breakdown into mechanical and non-mechanical causes; soft-tissue failure, loosening and periprosthetic infection play outstanding roles. Each type of failure can be associated to a specific prosthetic component: To avoid soft tissue failure, muscular connection to the prosthesis is essential; to avoid loosening, the anchoring technique on the stem is crucial; to prevent infection, the surface condition or possibly the coating of the prosthesis seem to play major roles. Some fully-fledged proximal femoral replacement systems have become established on the market and have similar clinical outcomes. However, there are significant differences in anchoring techniques, modularity or module connections and soft tissue connection. In any case, the high failure rates show that there is great potential for future developments. Innovative suggestions for each component are certainly possible through cross-linking to already functioning systems. Together with new findings from basic research, future systems should be able to significantly reduce the rate of prosthetic failures., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Animal fracture models, primarily performed in rats, are crucial to investigate normal and pathological bone healing. However, results of biomechanical testing representing a major outcome measure show high standard deviations often precluding statistical significance. Therefore, the aim of our study was a systematical examination of biomechanical characteristics of rat femurs during three-point bending. Furthermore, we tried to reduce variation of results by individually adapting the span of bearing and loading areas to the bone's length., Methods: We examined 40 paired femurs of male Wistar-rats by DXA (BMD and BMC of the whole femur) and pQCT-scans at the levels of bearing and loading areas of the subsequent biomechanical three-point bending test. Individual adjustment of bearing and loading bars was done respecting the length of each specimen. Subgroups of light (< 400 g, n = 22) and heavy (> 400 g, n = 18) animals were formed and analysed separately. We furthermore compared the results of the individualised bending-setting to 20 femurs tested with a fix span of 15 mm., Results: Femurs showed a length range of 34 to 46 mm. The failure loads ranged from 116 to 251 N (mean 175.4 ± 45.2 N; heavy animals mean 221 ± 18.9 N; light animals mean 138.1 ± 16.4 N) and stiffness ranged from 185 N/mm to 426 N/mm (mean 315.6 ± 63 N/mm; heavy animals mean 358.1 ± 34.64 N/mm; light animals mean 280.8 ± 59.85 N/mm). The correlation of densitometric techniques and failure loads was high (DXA R 2  = 0.89 and pQCT R 2  = 0.88). In comparison to femurs tested with a fix span, individual adaptation of biomechanical testing homogenized our data significantly. Most notably, the standard deviation of failure loads (221 ± 18.95 N individualized setting vs. 205.5 ± 30.36 N fixed) and stiffness (358.1 ± 34.64 N/mm individualized setting vs. 498.5 ± 104.8 N/mm fixed) was reduced by at least one third., Conclusions: Total variation observed in any trait reflects biological and methodological variation. Precision of the method hence affects the statistical power of the study. By simply adapting the setting of the biomechanical testing, interindividual variation could be reduced, which improves the precision of the method significantly.

Background: In the Ponseti treatment of idiopathic clubfoot, children are generally provided with a standard foot abduction orthosis (FAO). A significant proportion of these patients experience irresolvable problems with the FAO leading to therapeutic non-compliance and eventual relapse. Accordingly, these patients were equipped with a unilateral lower leg orthosis (LLO) developed in our institution. The goal of this retrospective study was to determine compliance with and the efficacy of the LLO as an alternative treatment measure. The minimum follow-up was 5 years., Results: A total of 45 patients (75 ft) were retrospectively registered and included in the study. Compliance with the bracing protocol was 91% with the LLO and 46% with the FAO. The most common problems with the FAO were sleep disturbance (50%) and cutaneous problems (45%). Nine percent of patients experienced sleep disturbance, and no cutaneous problems occurred with the LLO. Thirteen percent of patients being treated with an FAO until the age of four (23 patients; 40 ft) underwent surgery because of relapse, defined by rigid recurrence of any of the components of a clubfoot. Fourteen percent of patients being treated with an LLO (22 patients; 35 ft), mostly following initial treatment with an FAO, experienced recurrence., Conclusion: Changing from FAO to LLO at any point during treatment did not result in an increased rate of surgery and caused few problems.

Background: Existing preclinical murine models often fail to predict effects of anti-cancer drugs. In order to minimize interspecies-differences between murine hosts and human bone tumors of in vivo xenograft platforms, we tissue-engineered a novel orthotopic humanized bone model., Methods: Orthotopic humanized tissue engineered bone constructs (ohTEBC) were fabricated by 3D printing of medical-grade polycaprolactone scaffolds, which were seeded with human osteoblasts and embedded within polyethylene glycol-based hydrogels containing human umbilical vein endothelial cells (HUVECs). Constructs were then implanted at the femur of NOD-scid and NSG mice. NSG mice were then bone marrow transplanted with human CD34  +  cells. Human osteosarcoma (OS) growth was induced within the ohTEBCs by direct injection of Luc-SAOS-2 cells. Tissues were harvested for bone matrix and marrow morphology analysis as well as tumor biology investigations. Tumor marker expression was analyzed in the humanized OS and correlated with the expression in 68 OS patients utilizing tissue micro arrays (TMA)., Results: After harvesting the femurs micro computed tomography and immunohistochemical staining showed an organ, which had all features of human bone. Around the original mouse femur new bone trabeculae have formed surrounded by a bone cortex. Staining for human specific (hs) collagen type-I (hs Col-I) showed human extracellular bone matrix production. The presence of nuclei staining positive for human nuclear mitotic apparatus protein 1 (hs NuMa) proved the osteocytes residing within the bone matrix were of human origin. Flow cytometry verified the presence of human hematopoietic cells. After injection of Luc-SAOS-2 cells a primary tumor and lung metastasis developed. After euthanization histological analysis showed pathognomic features of osteoblastic OS. Furthermore, the tumor utilized the previously implanted HUVECS for angiogenesis. Tumor marker expression was similar to human patients. Moreover, the recently discovered musculoskeletal gene C12orf29 was expressed in the most common subtypes of OS patient samples., Conclusion: OhTEBCs represent a suitable orthotopic microenvironment for humanized OS growth and offers a new translational direction, as the femur is the most common location of OS. The newly developed and validated preclinical model allows controlled and predictive marker studies of primary bone tumors and other bone malignancies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aims: Asphericity of the femoral head-neck junction is common in cam-type femoroacetabular impingement (FAI) and usually quantified using the alpha angle on radiographs or MRI. The aim of this study was to determine the natural alpha angle in a large cohort of patients by continuous circumferential analysis with CT., Methods: CT scans of 1312 femurs of 656 patients were analyzed in this cross-sectional study. There were 362 men and 294 women. Their mean age was 61.2 years (18 to 93). All scans had been performed for reasons other than hip disease. Digital circumferential analysis allowed continuous determination of the alpha angle around the entire head-neck junction. All statistical tests were conducted two-sided; a p-value < 0.05 was considered statistically significant., Results: The mean maximum alpha angle for the cohort was 59.0° (sd 9.4). The maximum was located anterosuperiorly at 01:36 on the clock face, with two additional maxima of asphericity at the posterior and inferior head-neck junction. The mean alpha angle was significantly larger in men (59.4°, sd 8.0) compared with women (53.5°, sd 7.4°; p = 0.0005), and in Caucasians (60.7°, sd 9.0°) compared with Africans (56.3°, sd 8.0; p = 0.007) and Asians (50.8°, sd 7.2; p = 0.0005). The alpha angle showed a weak positive correlation with age (p < 0.05). If measured at commonly used planes of the radially reconstructed CT or MRI, the alpha angle was largely underestimated; measurement at the 01:30 and 02:00 positions showed a mean underestimation of 4° and 6°, respectively., Conclusion: This study provides important data on the normal alpha angle dependent on age, gender, and ethnic origin. The normal alpha angle in men is > 55°, and this should be borne in mind when making a diagnosis of cam-type morphology. Cite this article: Bone Joint J 2018;100-B:570-8.

Objectives: Rat fracture models are extensively used to characterize normal and pathological bone healing. Despite, systematic research on inter- and intra-individual differences of common rat bones examined is surprisingly not available. Thus, we studied the biomechanical behaviour and radiological characteristics of the humerus, the tibia and the femur of the male Wistar rat-all of which are potentially available in the experimental situation-to identify useful or detrimental biomechanical properties of each bone and to facilitate sample size calculations., Methods: 40 paired femura, tibiae and humeri of male Wistar rats (10-38 weeks, weight between 240 and 720 g) were analysed by DXA, pQCT scan and three-point-bending. Bearing and loading bars of the biomechanical setup were adapted percentually to the bone's length. Subgroups of light (skeletal immature) rats under 400 g (N = 11, 22 specimens of each bone) and heavy (mature) rats over 400 g (N = 9, 18 specimens of each bone) were formed and evaluated separately., Results: Radiologically, neither significant differences between left and right bones, nor a specific side preference was evident. Mean side differences of the BMC were relatively small (1-3% measured by DXA and 2.5-5% by pQCT). Over all, bone mineral content (BMC) assessed by DXA and pQCT (TOT CNT, CORT CNT) showed high correlations between each other (BMC vs. TOT and CORT CNT: R 2  = 0.94-0.99). The load-displacement diagram showed a typical, reproducible curve for each type of bone. Tibiae were the longest bones (mean 41.8 ± 4.12 mm) followed by femurs (mean 38.9 ± 4.12 mm) and humeri (mean 29.88 ± 3.33 mm). Failure loads and stiffness ranged from 175.4 ± 45.23 N / 315.6 ± 63.00 N/mm for the femurs, 124.6 ± 41.13 N / 260.5 ± 59.97 N/mm for the humeri to 117.1 ± 33.94 N / 143.8 ± 36.99 N/mm for the tibiae. Smallest interindividual differences were observed in failure loads of the femurs (CV% 8.6) and tibiae (CV% 10.7) of heavy animals, light animals showed good consistency in failure loads of the humeri (CV% 7.7). Most consistent results of both sides (left vs. right) in failure loads were provided by the femurs of light animals (mean difference 4.0 ± 2.8%); concerning stiffness, humeri of heavy animals were most consistent (mean difference of 6.2 ± 5%). In general, the failure loads showed strong correlations to the BMC (R 2  = 0.85-0.88) whereas stiffness correlated only moderate, except for the humerus (BMC vs. stiffness: R 2  = 0.79)., Discussion: Altogether, the rat's femur of mature specimens showed the most accurate and consistent radiological and biomechanical results. In synopsis with the common experimental use enabling comparison among different studies, this bone offers ideal biomechanical conditions for three point bending experiments. This can be explained by the combination of a superior aspect ratio and a round and long, straight morphology, which satisfies the beam criteria more than other bones tested.

Background: The purpose of this study was to investigate whether pathological fractures (PF) influence the prognosis of patients with osteosarcoma (OS) or Ewing tumor (ET) regarding 5-year survival, occurrence of metastases, and local recurrence., Methods: We retrospectively analyzed 205 patients with metastatic and nonmetastatic OS or ET. Survival analysis was performed for all patients and differentiated for patients with OS (n = 127) and ET (n = 78) as well as for adults (n = 101) and children (n = 104)., Results: Patients with PF showed survival rates of 64% compared to 83% for those without PF (p = 0.023). Local recurrence occurred in 7% of the patients without and in 24% of those with PF (p = 0.023). In patients with ET and in children, survival analysis showed no significant difference between patients with and without PF in survival and local recurrence rates. In patients with OS, survival rate decreased from 83 to 59% (p = 0.024) and local recurrence rate increased from 13 to 30% (p = 0.042). In adults, survival rate decreased from 78 to 51% (p = 0.004) and local recurrence rate increased from 13 to 42% (p < 0.001). In multivariate analysis, age and PF were associated with inferior survival., Conclusion: This study suggests that the occurrence of PF has a negative impact on survival and implicates an increased risk of local recurrence. In children and in patients with ET, PF did not have a prognostic impact., (© 2018 S. Karger AG, Basel.)

Background: A high percentage of closed femur fractures have slight comminution. Using micro-CT (μCT), multiple fragment segmentation is much more difficult than segmentation of unfractured or osteotomied bone. Manual or semi-automated segmentation has been performed to date. However, such segmentation is extremely laborious, time-consuming and error-prone. Our aim was to therefore apply a fully automated segmentation algorithm to determine μCT parameters and examine their association with biomechanics., Methods: The femura of 64 rats taken after randomised inhibitory or neutral medication, in terms of the effect on fracture healing, and controls were closed fractured after a Kirschner wire was inserted. After 21 days, μCT and biomechanical parameters were determined by a fully automated method and correlated (Pearson's correlation)., Results: The fully automated segmentation algorithm automatically detected bone and simultaneously separated cortical bone from callus without requiring ROI selection for each single bony structure. We found an association of structural callus parameters obtained by μCT to the biomechanical properties. However, results were only explicable by additionally considering the callus location., Conclusions: A large number of slightly comminuted fractures in combination with therapies that influence the callus qualitatively and/or quantitatively considerably affects the association between μCT and biomechanics. In the future, contrast-enhanced μCT imaging of the callus cartilage might provide more information to improve the non-destructive and non-invasive prediction of callus mechanical properties. As studies evaluating such important drugs increase, fully automated segmentation appears to be clinically important.

With a dislocation rate of up to 35% after revision total hip arthroplasty (THA), instability is one of the major causes why this procedure fails. Independent factors for patients at risk are age, sex, and the type of revision needed. The surgical approach, implant choice, and positioning of the components are factors that the surgeon can influence to keep the dislocation rate low. Large femoral heads or double mobility (DM) cups can increase the stability of the joint. After detailed failure analysis, targeted use of different technical innovations enhances stability in revision THA and prevents further revisions.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) have long been suspected of negatively affecting fracture healing, although numerous disputes still exist and little data are available regarding diclofenac. Glucocorticoids interfere in this process over a similar and even broader mechanism of action. As many previously conducted studies evaluated either morphological changes or biomechanical properties of treated bones, the conjunction of both structural measures is completely missing. Therefore, it was our aim to evaluate the effects of diclofenac and prednisolone on the fracture callus biomechanically, morphologically and by 3-dimensional (3D) microstructural analysis., Methods: Femura of diclofenac-, prednisolone- or placebo-treated rats were pinned and a closed transverse fracture was generated. After 21 days, biomechanics, micro-CT (μCT) and histology were examined., Results: The diclofenac group showed significantly impaired fracture healing compared with the control group by biomechanics and μCT (e.g. stiffness: 57.31 ± 31.11 N/mm vs. 122.44 ± 81.16 N/mm, p = 0.030; callus volume: 47.05 ± 15.67 mm3 vs. 67.19 ± 14.90 mm3, p = 0.037, trabecular thickness: 0.0937 mm ± 0.003 vs. 0.0983 mm ± 0.003, p = 0.023), as confirmed by histology. Biomechanics of the prednisolone group showed obviously lower absolute values than the control group. These alterations were confirmed in conjunction with μCT and histology., Conclusions: The inhibiting effects of both substances were not only mediated by absolute parameters (e.g. breaking load, BV), but we have shown, for the first time, that additional changes occurred in the microstructural bony network. Especially in patients at risk for delayed bone healing (arteriosclerosis, diabetes mellitus, smoking), the administration of these drugs should be weighed carefully.

Low molecular weight heparin (LMWH) is routinely used to prevent thromboembolism in orthopaedic surgery, especially in the treatment of fractures or after joint-replacement. Impairment of fracture-healing due to increased bone-desorption, delayed remodelling and lower calcification caused by direct osteoclast stimulation is a well-known side effect of unfractioned heparin. However, the effect of LMWH is unclear and controversial. Recent studies strongly suggest impairment of bone-healing in-vitro and in animal models, characterized by a significant decrease in volume and quality of new-formed callus. Since October 2008, Rivaroxaban (Xarelto) is available for prophylactic use in elective knee- and hip-arthroplasty. Recently, some evidence has been found indicating an in vitro dose independent reduction of osteoblast function after Rivaroxaban treatment. In this study, the possible influence of Rivaroxaban and Enoxaparin on bone-healing in vivo was studied using a standardized, closed rodent fracture-model. 70 male Wistar-rats were randomized to Rivaroxaban, Enoxaparin or control groups. After pinning the right femur, a closed, transverse fracture was produced. 21 days later, the animals were sacrificed and both femora harvested. Analysis was done by biomechanical testing (three-point bending) and micro CT. Both investigated substances showed histomorphometric alterations of the newly formed callus assessed by micro CT analysis. In detail the bone (callus) volume was enhanced (sign. for Rivaroxaban) and the density reduced. The bone mineral content was enhanced accordingly (sign. for Rivaroxaban). Trabecular thickness was reduced (sign. for Rivaroxaban). Furthermore, both drugs showed significant enlarged bone (callus) surface and degree of anisotropy. In contrast, the biomechanical properties of the treated bones were equal to controls. To summarize, the morphological alterations of the fracture-callus did not result in functionally relevant deficits.

Periprosthetic fractures of hip and knee prostheses are gaining clinical significance due to the increasing numbers of of primary arthroplasties. Additionally, these fractures are often associated with poor bone quality or present in patients after multiple revision procedures and concomitant excessive bone defects precluding those patients to be adequately treated by conventional osteosynthesis. Revision implants provide a wide range of options for the treatment of these fractures in order to achieve good clinical results. In the acetabular region cavitary defects associated with periprosthetic fractures can be treated by the use of megacups. Extensive segmental defects and pelvic discontinuity necessitate the use of cups with additional iliac support or even customized implants. Proximal femoral fractures can usually be fixed with modular stems and diaphyseal anchorage. Periprosthetic knee joint fractures can be treated with revision implants with modular sleeves or augment-combinations allowing sufficient bridging of bony defects. Functional reconstruction or refixation of the extensor mechanism is of crucial importance.

Objectives: Venous thromboembolism (VTE) is a major potential complication following orthopaedic surgery. Subcutaneously administered enoxaparin has been used as the benchmark to reduce the incidence of VTE. However, concerns have been raised regarding the long-term administration of enoxaparin and its possible negative effects on bone healing and bone density with an increase of the risk of osteoporotic fractures. New oral anticoagulants such as rivaroxaban have recently been introduced, however, there is a lack of information regarding how these drugs affect bone metabolism and post-operative bone healing., Methods: We measured the migration and proliferation capacity of mesenchymal stem cells (MSCs) under enoxaparin or rivaroxaban treatment for three consecutive weeks, and evaluated effects on MSC mRNA expression of markers for stress and osteogenic differentiation., Results: We demonstrate that enoxaparin, but not rivaroxaban, increases the migration potential of MSCs and increases their cell count in line with elevated mRNA expression of C-X-C chemokine receptor type 4 (CXCR4), tumor necrosis factor alpha (TNFα), and alpha-B-crystallin (CryaB). However, a decrease in early osteogenic markers (insulin-like growth factors 1 and 2 (IGF1, IGF2), bone morphogenetic protein2 (BMP2)) indicated inhibitory effects on MSC differentiation into osteoblasts caused by enoxaparin, but not by rivaroxaban., Conclusions: Our findings may explain the adverse effects of enoxaparin treatment on bone healing. Rivaroxaban has no significant impact on MSC metabolism or capacity for osteogenic differentiation in vitro.Cite this article: Dr H. Pilge. Enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing. Bone Joint Res 2016;5:95-100. DOI: 10.1302/2046-3758.53.2000595., (© 2016 Pilge et al.)

Background: Low-molecular-weight heparins (e.g. Enoxaparin) are widely used to prevent venous thromboembolism after orthopaedic surgery, but there are reports about serious side effects including reduction in bone density and strength. In recent years new oral antithrombotic drugs (e.g. direct Factor Xa-inhibitor, Rivaroxaban) have been used to prevent venous thromboembolism. However, there is lack of information on the effects of these new drugs on human mesenchymal stromal cells during osteogenic differentiation and, therefore, effects during postoperative bone healing., Methods: We evaluated the effects of Rivaroxaban and Enoxaparin on the proliferation, mRNA and surface receptor expression as well as differentiation capacity of primary human mesenchymal stromal cells during their osteogenic differentiation., Results: Enoxaparin, but not Rivaroxaban treatment significantly increased human mesenchymal stromal cell (hMSC) proliferation during the first week of osteogenic differentiation while suppressing osteogenic marker genes, surface receptor expression and calcification., Conclusions: This is the first paper to demonstrate that Rivaroxaban had no significant influence on hMSC differentiation towards the osteogenic lineage, indicating a less affected bone healing process compared with Enoxaparin in vitro. Based on these findings Rivaroxaban seems to be superior to Enoxaparin in early stages of bone healing in vitro.

Background: The diagnosis and treatment of periprosthetic joint infection (PJI) remain true clinical challenges. PJI diminishes therapeutic success, causes dissatisfaction for the patient and medical staff, and often requires extensive surgical revision(s). At the present time, an extensive multimodal algorithmic approach is used to avoid time- and cost-consuming diagnostic aberrations. However, especially in the case of the frequent and clinically most relevant "low-grade" PJI, the current diagnostic "gold standard" has reached its limits., Evaluation: Synovial biomarkers are thought to close this diagnostic gap, hopefully enabling the safe differentiation among aseptic, (chronic) septic, implant allergy-related and the arthrofibrotic genesis of symptomatic arthroplasty. Therefore, joint aspiration for obtaining synovial fluid is preferred over surgical synovial tissue biopsy because of the faster results, greater practicability, greater patient safety, and lower costs. In addition to the parameters synovial IL-6, CRP, and leukocyte esterase, novel biomarkers such as antimicrobial peptides and other proinflammatory cytokines are currently highlighted because of their very high to excellent diagnostic accuracy., Conclusion: Independent multicenter validation studies are required to show whether a set of different innovative synovial fluid biomarkers rather than a few single parameters is favorable for a safe "one-stop shop" differential diagnosis of PJI.

The aim of this study was to analyse the gait pattern, muscle force and functional outcome of patients who had undergone replacement of the proximal tibia for tumour and alloplastic reconstruction of the extensor mechanism using the patellar-loop technique. Between February 1998 and December 2009, we carried out wide local excision of a primary sarcoma of the proximal tibia, proximal tibial replacement and reconstruction of the extensor mechanism using the patellar-loop technique in 18 patients. Of these, nine were available for evaluation after a mean of 11.6 years (0.5 to 21.6). The strength of the knee extensors was measured using an Isobex machine and gait analysis was undertaken in our gait assessment laboratory. Functional outcome was assessed using the American Knee Society (AKS) and Musculoskeletal Tumor Society (MSTS) scores. The gait pattern of the patients differed in ground contact time, flexion heel strike, maximal flexion loading response and total sagittal plane excursion. The mean maximum active flexion was 91° (30° to 110°). The overall mean extensor lag was 1° (0° to 5°). The mean extensor muscle strength was 25.8% (8.3% to 90.3%) of that in the non-operated leg (p < 0.001). The mean functional scores were 68.7% (43.4% to 83.3%) (MSTS) and 71.1 (30 to 90) (AKS functional score). In summary, the results show that reconstruction of the extensor mechanism using this technique gives good biomechanical and functional results. The patients' gait pattern is close to normal, except for a somewhat stiff knee gait pattern. The strength of the extensor mechanism is reduced, but sufficient for walking., (©2015 The British Editorial Society of Bone & Joint Surgery.)