Publications by authors named "Reinhard Windhager"

292 Publications

Galectin network in osteoarthritis: galectin-4 programs a pathogenic signature of gene and effector expression in human chondrocytes in vitro.

Histochem Cell Biol 2021 Nov 30. Epub 2021 Nov 30.

Karl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Galectin-4 (Gal-4) is a member of the galectin family, which have been identified as galactose-binding proteins. Gal-4 possesses two tandem repeat carbohydrate recognition domains and acts as a cross-linking bridge in sulfatide-dependent glycoprotein routing. We herein document its upregulation in osteoarthritis (OA) in correlation with the extent of cartilage degradation in vivo. Primary human OA chondrocytes in vitro respond to carbohydrate-inhibitable Gal-4 binding with the upregulation of pro-degradative/-inflammatory proteins such as interleukin-1β (IL-1β) and matrix metalloproteinase-13 (MMP-13), as documented by RT-qPCR-based mRNA profiling and transcriptome data processing. Activation of p65 by phosphorylation of Ser536 within the NF-κB pathway and the effect of three p65 inhibitors on Gal-4 activity support downstream involvement of such signaling. In 3D (pellet) cultures, Gal-4 presence causes morphological and biochemical signs of degradation. Taken together, our findings strongly support the concept of galectins acting as a network in OA pathogenesis and suggest that blocking their activity in disease progression may become clinically relevant in the future.
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http://dx.doi.org/10.1007/s00418-021-02053-1DOI Listing
November 2021

Nineteen percent of meniscus repairs are being revised and failures frequently occur after the second postoperative year: a systematic review and meta-analysis with a minimum follow-up of 5 years.

Knee Surg Sports Traumatol Arthrosc 2021 Oct 20. Epub 2021 Oct 20.

Department of Orthopaedic and Trauma Surgery, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.

Purpose: Meniscus repair has gained increasing interest over the last two decades as loss of meniscus tissue predisposes to early onset knee arthritis. Although there are many reports of meniscus repair outcome in short-term studies, data on the long-term outcome of meniscus repair are still scarce. The purpose of this meta-analysis was to evaluate the overall failure rate of meniscus repair with a minimum follow-up of 5 years. Additionally, possible factors influencing meniscus repair outcome were assessed.

Methods: PubMed and Scopus were searched for studies of the last 20 years reporting on meniscus repair outcome with a minimum follow-up of 5 years. The study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search terms used for this study were ([meniscus OR meniscal] AND repair). Titles and abstracts were evaluated by two authors independently. Using meta package of R (version 3.6.2), random-effect models were performed to pool failure rates. Subgroup analyses were performed and effect estimates in form of an odds ratio with 95% CIs were established.

Results: In total, 12 studies with 864 patients were included. Degenerative tears were excluded in two studies and one study only included traumatic meniscus tears. Other studies did not state whether the cause of meniscus tear was degenerative or traumatic. Studies reporting meniscus repair outcome on root repairs, revision anterior cruciate ligament reconstruction, discoid menisci or ramp lesions were excluded. Revision surgery was used as failure definition in all included studies. The overall failure rate of meniscal repair at a mean follow-up of 86 months was 19.1%. There was no significant difference in meniscus repair outcome when performed in combination with anterior cruciate ligament reconstruction compared to isolated meniscus repair (18.7% vs. 28%; n.s.) or when performed on the lateral meniscus compared to the medial meniscus (19.5% vs. 24.4%; n.s.). There was no significant difference of meniscus repair outcome between vertical/longitudinal tears and bucket-handle tears (n.s.). Thirty-six percent of meniscus repair failures occur after the second postoperative year. The only significant finding was that inside-out repair results in a lower failure rate compared to all-inside repair (5.6% vs. 22.3%; p = 0.009) at 5 years.

Conclusion: The overall meniscus repair failure rate remains nineteen percent in long-term studies. The cause of failure is poorly documented, and it remains unclear whether failure of the meniscus repair itself or additional adjacent tears lead to revision surgery. Despite the given technical advantages of all-inside repair devices, this meta-analysis cannot demonstrate superior outcomes compared to inside-out or outside-in repair at 5 years.

Level Of Evidence: IV.
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http://dx.doi.org/10.1007/s00167-021-06770-xDOI Listing
October 2021

On Measuring Implant Fixation Stability in ACL Reconstruction.

Sensors (Basel) 2021 Oct 6;21(19). Epub 2021 Oct 6.

AO Research Institute Davos, 7270 Davos, Switzerland.

Numerous methods and devices are available for implant fixation in anterior cruciate ligament (ACL) reconstruction. Biomechanical data indicate high variability in fixation stability across different devices. This study aims to provide a better insight into measuring the structural characteristics and mechanical behavior of ACL implant fixations. Fourteen human tibial specimens with reconstructed ACLs were subjected to progressively increasing dynamic loading until failure. The motions of the tibia, the proximal and distal graft ends, as well as the testing frame and actuator, were continuously recorded via a motion tracking system. Significantly higher displacements of the machine actuator (1.0 mm at graft slippage onset, and 12.2 mm at ultimate load) were measured compared to the displacements of the proximal (0.8 and 4.3 mm, respectively) and distal graft (0.1 and 3.4 mm, respectively) ends. The displacements measured at different sites showed significant correlations. The provided data suggest significant and systematic inaccuracies in the stiffness and slippage of the fixation when using machine displacement, as commonly reported in the literature. The assessment of the distal graft displacement excludes the artifactual graft elongation, and most accurately reflects the graft slippage onset indicating clinical failure. Considering the high displacement at the ultimate load, the ultimate load could be used as a standardized variable to compare different fixation methods. However, the ultimate load alone is not sufficient to qualitatively describe fixation stability.
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http://dx.doi.org/10.3390/s21196632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513052PMC
October 2021

Results in the surgical treatment of aneurysmal bone cysts - A retrospective data analysis.

Orthop Traumatol Surg Res 2021 Oct 1:103095. Epub 2021 Oct 1.

Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna.

Background: Aneurysmal bone cysts (ABC) are benign tumors mostly occurring in children and young adults. Different open and minimal invasive surgical approaches have been proposed for the treatment of ABCs and yet no consensus is defined to date. The aim of this study was to retrospectively review data of a large single center series of ABCs with patients treated by open curettage with or without filling of the cavity or en-bloc resection. Questions/purposes We asked: (1) What was the local recurrence rate of ABC after surgical treatment at our institution? (2) What were positive or negative predictors for local recurrence? (3) Was there a benefit from adjuvant burring, phenolization or filling, respectively? (4) Where there changes in recurrence free survival in different time periods of primary surgery?

Methods: By retrospective data analysis of the Vienna Bone and Soft Tissue Tumor Registry, 123 patients surgically treated for primary aneurysmal bone cysts were identified. After exclusion of 33 patients (27%) due to a postoperative follow up below one year, 90 patients who were treated for primary ABCs between 1986 and 2009 were evaluated. These included 50 males and 40 females with a mean age of 16 years (SD 10 years; range: 2 to 51 years). The mean follow-up was 99 months. (SD 72 months, range: 13 to 329 months) RESULTS: Curettage was performed in 84 patients, while 45 patients received adjuvant phenolization. Local recurrence occurred in 28 patients after a mean time of 16 months, with a corresponding local recurrence free survival (RFS) of 83% after one year, 77% after 2 years and 66% after 5 years. ABCs located in hands and feet (p=0.044) showed a superior RFS, while younger patients (p=0.001) displayed an inferior RFS. Regarding adjuvant surgical techniques, mechanical cavity burring (p=0.004) and filling with autologous cancellous bone graft (p=0.024) showed protective effects on RFS. Patients treated between 1986 and 1999 (n=47) had a higher RFS than patients treated between 2000 and 2009 (n=43, p=0.011), as surgeons and surgical indications changed over time.

Conclusion: Although curettage, burring, phenolization and reconstruction with bone grafts came with a relatively high risk of local recurrence, open surgery is still justified in aggressively growing ABCs of critical localizations.

Level Of Evidence: IV; therapeutic study.
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http://dx.doi.org/10.1016/j.otsr.2021.103095DOI Listing
October 2021

Thermal Effects during Bone Preparation and Insertion of Osseointegrated Transfemoral Implants.

Sensors (Basel) 2021 Sep 18;21(18). Epub 2021 Sep 18.

Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, 1090 Vienna, Austria.

Background: The preparation of bone for the insertion of an osseointegrated transfemoral implant and the insertion process are performed at very low speeds in order to avoid thermal damages to bone tissue which may potentially jeopardize implant stability. The aim of this study was to quantify the temperature increase in the femur at different sites and insertion depths, relative to the final implant position during the stepwise implantation procedure.

Methods: The procedure for installation of the osseointegrated implant was performed on 24 femoral specimens. In one specimen of each pair, the surgery was performed at the clinically practiced speed, while the speed was doubled in the contralateral specimen. Six 0.075 mm K fine gauge thermocouples (RS Components, Sorby, UK) were inserted into the specimen at a distance of 0.5 mm from the final implant surface, and six were inserted at a distance of 1.0 mm.

Results: Drilling caused a temperature increase of <2.5 °C and was not statistically significantly different for most drill sizes (0.002 < < 0.845). The mean increase in temperature during thread tapping and implant insertion was <5.0 °C, whereas the speed had an effect on the temperature increase during thread tapping.

Conclusions: Drilling is the most time-consuming part of the surgery. Doubling the clinically practiced speed did not generate more heat during this step, suggesting the speed and thus the time- and cost-effectiveness of the procedure could be increased. The frequent withdrawal of the instruments and removal of the bone chips is beneficial to prevent temperature peaks, especially during thread tapping.
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http://dx.doi.org/10.3390/s21186267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472893PMC
September 2021

Serum Inflammatory Biomarkers in the Diagnosis of Periprosthetic Joint Infections.

Biomedicines 2021 Sep 1;9(9). Epub 2021 Sep 1.

Department of Orthopaedics and Trauma Surgery, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria.

Accurate preoperative diagnosis of periprosthetic joint infections (PJIs) can be very challenging, especially in patients with chronic PJI caused by low-virulence microorganisms. Serum parameters, such as serum C-reactive protein (CRP) or the erythrocyte sedimentation rate (ESR), are-among other diagnostic test methods-widely used to distinguish septic from aseptic failure after total hip or knee arthroplasty and are recommended by the AAOS in the preoperative setting. However, they are systemic parameters, and therefore, unspecific. Nevertheless, they may be the first and occasionally the only preoperative indication, especially when clinical symptoms are lacking. They are easy to obtain, cheap, and are available worldwide. In the last decade, different novel serum biomarkers (percentage of neutrophils, neutrophils to lymphocytes ratio, platelet count to mean platelet volume ratio, fibrinogen, D-Dimer, Il-6, PCT) were investigated to find a more specific and accurate serum parameter in the diagnosis of PJI. This article reviews the diagnostic value of established (serum CRP, ESR, WBC) and 'novel' serum inflammatory biomarkers (fibrinogen, D-dimer, interleukin-6 (IL-6), procalcitonin, percentage of neutrophils (%N), neutrophils to lymphocytes ratio (NLR), platelet count to mean platelet volume ratio (PC/mPV)) for the preoperative diagnosis of periprosthetic joint infections.
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http://dx.doi.org/10.3390/biomedicines9091128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467465PMC
September 2021

Synthetic T-weighted images of the lumbar spine derived from an accelerated T mapping sequence: Comparison to conventional Tw turbo spin echo.

Magn Reson Imaging 2021 Dec 23;84:92-100. Epub 2021 Sep 23.

Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Austria; Christian Doppler Laboratory for Clinical Molecular MR Imaging (MOLIMA), High Field MR Center, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Austria.

Objectives: To evaluate the diagnostic usefulness of synthetic T-weighted images of the lumbar spine derived from ten-fold undersampled k-space data using GRAPPATINI, a combination of a model-based approach for rapid T and M quantification (MARTINI) extended by generalized autocalibrating partial parallel acquistion (GRAPPA).

Materials And Methods: Overall, 58 individuals (26 female, mean age 23.3 ± 8.1 years) were examined at 3 Tesla with sagittal and axial Tw turbo spin echo (TSE) sequences compared to synthetic Tweighted contrasts derived at identical effective echo times and spatial resolutions. Two blinded readers graded disk degeneration and evaluated the lumbar intervertebral disks for present herniation or annular tear. One reader reassessed all studies after four weeks. Weighted kappa statistics were calculated to assess inter-rater and intra-rater agreement. Also, all studies were segmented manually by one reader to compute contrast ratios (CR) and contrast-to-noise ratios (CNR) of the nucleus pulposus and the annulus fibrosus.

Results: Overall, the CR was 4.45 ± 1.80 and CR was 4.71 ± 2.14. Both correlated (rsp = 0.768;p < 0.001) and differed (0.26 ± 1.38;p = 0.002) significantly. The CNR was 1.73 ± 0.52 and CNR was 1.63 ± 0.50. Both correlated (rsp = 0.875;p < 0.001) and differed (-0.10 ± 0.25;p < 0.001) significantly. The inter-rater agreement was substantial to almost perfect (κ = 0.808-0.925) with the intra-rater agreement also substantial to almost perfect (κ = 0.862-0.963). The area under the curve of the receiver operating characteristics assessing disk herniation or annular tear ranged from 0.787 to 0.892.

Conclusions: This study concludes that synthetic images derived by GRAPPATINI can be used for clinical routine assessment with inter-rater and intra-rater agreements comparable to conventional Tw TSE.
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http://dx.doi.org/10.1016/j.mri.2021.09.011DOI Listing
December 2021

Establishment of a human three-dimensional chip-based chondro-synovial coculture joint model for reciprocal cross talk studies in arthritis research.

Lab Chip 2021 10 26;21(21):4128-4143. Epub 2021 Oct 26.

Faculty of Technical Chemistry, Vienna University of Technology, Getreidemarkt 9, 1060 Vienna, Austria.

Rheumatoid arthritis is characterised by a progressive, intermittent inflammation at the synovial membrane, which ultimately leads to the destruction of the synovial joint. The synovial membrane as the joint capsule's inner layer is lined with fibroblast-like synoviocytes that are the key player supporting persistent arthritis leading to bone erosion and cartilage destruction. While microfluidic models that model molecular aspects of bone erosion between bone-derived cells and synoviocytes have been established, RA's synovial-chondral axis has not yet been realised using a microfluidic 3D model based on human patient cultures. Consequently, we established a chip-based three-dimensional tissue coculture model that simulates the reciprocal cross talk between individual synovial and chondral organoids. When co-cultivated with synovial organoids, we could demonstrate that chondral organoids induce a higher degree of cartilage physiology and architecture and show differential cytokine response compared to their respective monocultures highlighting the importance of reciprocal tissue-level cross talk in the modelling of arthritic diseases.
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http://dx.doi.org/10.1039/d1lc00130bDOI Listing
October 2021

[Tumour arthroplasty].

Orthopade 2021 10 8;50(10):839-842. Epub 2021 Sep 8.

Universitätsklinik für Orthopädie und Unfallchirurgie, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090, Wien, Österreich.

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http://dx.doi.org/10.1007/s00132-021-04151-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8484240PMC
October 2021

Diagnostic accuracy of ultrasound-guided core needle biopsy versus incisional biopsy in soft tissue sarcoma: an institutional experience.

Sci Rep 2021 09 8;11(1):17832. Epub 2021 Sep 8.

Department of Orthopaedic Surgery, Medical University of Vienna, Vienna General Hospital, Währinger Gürtel 18-20, 1090, Vienna, Austria.

Core needle biopsy (CNB) is gaining in importance due to its advantages in the matter of patient morbidity, time and cost. Nevertheless, controversies still exist regarding the biopsy technique of choice for the accurate diagnosis of soft tissue sarcoma (STS). This retrospective cohort study compared the diagnostic performance between ultrasound-guided CNB and incisional biopsy (IB), both performed by orthopedic surgeons. The aims of the study were to answer the following questions: (1) Is ultrasound-guided CNB a highly reliable modality for diagnosing STSs? (2) Is CNB equally useful to IB for identifying histologic subtype? (3) Had patients who underwent CNB a reduced risk of complications? One-hundred and fifty-three patients who underwent resection of soft tissue sarcoma were classified into two groups according to biopsy technique prior to surgery; CNB group (n = 95) and IB group (n = 58). The final surgical specimens were in 40 patients liposarcoma (myxoid, pleomorphic and dedifferentiated), 39 undifferentiated pleomorphic sarcoma (UPS), 33 myxofibrosarcoma, 10 synovial sarcoma, 10 leiomyosarcoma and in the remaining 21 patients different soft tissue sarcoma entities. Sarcoma location of 71 patients was in the thigh, 19 in the lower leg, 22 in the upper arm and shoulder area; 10 in the knee and gluteal region, 9 in the thoracic region, the residual 12 in other body areas. Malignancy was correctly diagnosed in 87% (83 of 95) for the CNB group and 93% (54/58) for the IB group. Correct identification rate of histologic subtype was 80% (76 of 95) in the CNB group and 83% (48 of 58) in the IB group. There were no significant differences in the correct diagnosis rates of malignancy and subtype between the two techniques. No complications were seen in the CNB group, whereas 2 patients in whom IB was performed developed pulmonary embolism and 1 patient surgical site infection. Ultrasound-guided CNB is highly accurate and not inferior to IB in diagnosing the dignity of lesions and histologic subtype in patients with suspected STSs.
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http://dx.doi.org/10.1038/s41598-021-96953-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426501PMC
September 2021

Diagnosis and staging of malignant bone tumours in children: what is due and what is new?

J Child Orthop 2021 Aug;15(4):312-321

Department of Pediatric Orthopedics, Hospital Universitari Son Espases, Palma de Mallorca, Spain.

Purpose: Although malignant bone tumours in children are infrequent, it is important to know how to properly diagnose and stage them, in order to establish an adequate treatment.

Methods: We present a review of the diagnostic workflow of malignant bone tumours in children, including history and clinical examination, imaging, laboratory tests and biopsy techniques. Moreover, the two most commonly used staging systems are reviewed.

Results: History, clinical examination and laboratory tests are nonspecific for diagnosing malignant bone tumours in children. Radiographs remain the mainstay for initial diagnosis, with MRI the modality of choice for local assessment and staging. Fluorine-18 labelled fluoro-deoxy-glucose-positron emission tomography scans provide a noninvasive method to assess the aggressiveness of the tumour and to rule out metastasis and is replacing the use of the bone scintigraphy. Biopsy must be always performed under the direction of the surgeon who is to perform the surgical treatment and after all diagnostic evaluation has been done. Staging systems are useful to study the extent of the tumour and its prognosis. They are expected to evolve as we better understand new molecular and genetic findings.

Conclusion: When a malignant bone tumour is suspected in a child, it is essential to make a correct diagnosis and referral to an experienced centre. Following an appropriate workflow for diagnosis and staging facilitates, prompt access to treatment improves outcomes.

Level Of Evidence: Level V Expert opinion.
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http://dx.doi.org/10.1302/1863-2548.15.210107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381400PMC
August 2021

In vitro testing of silver-containing spacer in periprosthetic infection management.

Sci Rep 2021 08 26;11(1):17261. Epub 2021 Aug 26.

Department of Orthopedics, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Wien, Austria.

Deep infection is a serious complication in endoprosthetic surgery. In correlation to the patient local or systemic compromising factors conservative and surgical proceedings has to be evaluated. Systemic antibiotic therapy is the gold standard in infection management. Implanted silver-coated or silver-containing medical devices have been proven to their antimicrobial effectiveness since the 1990s by several investigators. The outcomes showed that long time implantation could cause damaging of the surrounding tissues, especially of adjacent nerves. The aim of our study was to evaluate the release of silver (I) ions from bone cement mixed with either nanosilver particles (AgNPs), different concentrations of silver sulfate (Ag2SO4) or from pure metallic silver strips. Therefore, we choose two methods: the first, called "static model", was chosen to evaluate the maximal accumulative concentration of silver (I) ions, with the second, called "dynamic model", we simulated a continuous reduction of the ions. In an additional test design, the different materials were evaluated for their antimicrobial activity using an agar gel diffusion assay. The outcome showed that neither the addition of 1% (w/w) nanosilver nor 0.1% silver sulfate (w/w) to polymethylmethacrylat bone cement has the ability to release silver (I) ions in a bactericidal/antifungal concentration. However, the results also showed that the addition of 0.5% (w/w) and 1% (w/w) silver sulfate (Ag2SO4) to bone cement is an effective amount of silver for use as a temporary spacer.
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http://dx.doi.org/10.1038/s41598-021-96811-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390469PMC
August 2021

Patient-Specific Implants for Pelvic Tumor Resections.

J Pers Med 2021 Jul 21;11(8). Epub 2021 Jul 21.

Division of Orthopaedics, Department of Orthopaedics and Trauma Surgery, Medical University of Vienna, 1090 Vienna, Austria.

Introduction Limb salvage surgery for periacetabular malignancies is technically demanding and associated with a considerable likelihood of postoperative complications and surgical revision. Reconstruction using custom-made implants represents the treatment of choice. This study was conducted to analyze treatment outcomes of custom-made implants in a single orthopaedic tumor center. Patients and Methods Twenty patients with a histologically verified periacetabular malignancy and a median follow up time of 5 (1-17) years were included. Results The median number of revision surgeries per patient was 1.5 (0-7). Complications were dislocations in 3 patients, aseptic loosening in 4 patients, deep infections in 9 patients, thromboembolic events in 5 patients and sciatic nerve lesions in 4 patients. Overall survival was 77% after one year, 69% after two years and 46% after five years. Median Harris Hip Score was 81 (37-92) points at last follow up. Conclusion Although internal hemipelvectomy and reconstruction using custom-made implants is linked with a high risk of postoperative complications, good functional outcomes can be regularly achieved. This information may help treating surgeons to find adequate indications, as eligible patients need to be critically selected and integrated into the decision-making process.
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http://dx.doi.org/10.3390/jpm11080683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399992PMC
July 2021

Diagnostic accuracy of neutrophil counts in histopathological tissue analysis in periprosthetic joint infection using the ICM, IDSA, and EBJIS criteria.

Bone Joint Res 2021 Aug;10(8):536-547

Department of Pathology, Medical University of Vienna, Vienna, Austria.

Aims: Histology is an established tool in diagnosing periprosthetic joint infections (PJIs). Different thresholds, using various infection definitions and histopathological criteria, have been described. This study determined the performance of different thresholds of polymorphonuclear neutrophils (≥ 5 PMN/HPF, ≥ 10 PMN/HPF, ≥ 23 PMN/10 HPF) , when using the European Bone and Joint Infection Society (EBJIS), Infectious Diseases Society of America (IDSA), and the International Consensus Meeting (ICM) 2018 criteria for PJI.

Methods: A total of 119 patients undergoing revision total hip (rTHA) or knee arthroplasty (rTKA) were included. Permanent histology sections of periprosthetic tissue were evaluated under high power (400× magnification) and neutrophils were counted per HPF. The mean neutrophil count in ten HPFs was calculated (PMN/HPF). Based on receiver operating characteristic (ROC) curve analysis and the z-test, thresholds were compared.

Results: Using the EBJIS criteria, a cut-off of ≥ five PMN/HPF showed a sensitivity of 93% (95% confidence interval (CI) 81 to 98) and specificity of 84% (95% CI 74 to 91). The optimal threshold when applying the IDSA and ICM criteria was ≥ ten PMN/HPF with sensitivities of 94% (95% CI 79 to 99) and 90% (95% CI 76 to 97), and specificities of 86% (95% CI 77 to 92) and 92% (95% CI 84 to 97), respectively. In rTKA, a better performance of histopathological analysis was observed in comparison with rTHA when using the IDSA criteria (p < 0.001).

Conclusion: With high accuracy, histopathological analysis can be supported as a confirmatory criterion in diagnosing periprosthetic joint infections. A threshold of ≥ five PMN/HPF can be recommended to distinguish between septic and aseptic loosening, with an increased possibility of detecting more infections caused by low-virulence organisms. However, neutrophil counts between one and five should be considered suggestive of infection and interpreted carefully in conjunction with other diagnostic test methods. Cite this article:  2021;10(8):536-547.
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http://dx.doi.org/10.1302/2046-3758.108.BJR-2021-0058.R1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414440PMC
August 2021

Proximal femoral reconstruction with modular megaprostheses in non-oncological patients.

Int Orthop 2021 10 14;45(10):2531-2542. Epub 2021 Jul 14.

Division of Orthopaedics, Department of Orthopaedics and Trauma Surgery, Medical University of Vienna, Vienna, Austria.

Introduction: Multiple revision hip arthroplasties and critical trauma might cause severe bone loss that requires proximal femoral replacement (PFR). The aim of this retrospective study was to analyse complication- and revision-free survivals of patients who received modular megaprostheses in an attempt to reconstruct massive non-neoplastic bone defects of the proximal femur. Questions/purposes (1) What were general complication rates and revision-free survivals following PFR? (2) What is the incidence of complication specific survivals? (3) What were risk factors leading to a diminished PFR survival?

Materials And Methods: Twenty-eight patients with sufficient follow-up after receiving a modular proximal femoral megaprosthesis were identified. The indications for PFR included prosthetic joint infection (PJI), periprosthetic fracture, aseptic loosening, non-union and critical femoral fracture. Complications were grouped according to the ISOLS-classification of segmental endoprosthetic failure by Henderson et al. RESULTS: Overall, the complication-free survival was 64.3% at one year, 43.2% at five years and 38.4% at ten years, with 16 patients (57%) suffering at least one complication. Complications were dislocation in eight patients (29%), PJI in 6 patients (21%), periprosthetic fracture in five patients (18%), and aseptic loosening in six patients (21%). Prosthesis stem cementation showed a lower risk for revision in a cox proportional hazard model (95% CI 0.04-0.93, HR 0.2, p = 0.04).

Conclusion: PFR with modular megaprostheses represents a viable last resort treatment with high complication rates for patients with severe proximal femoral bone loss due to failed arthroplasty or critical fractures. In revision arthroplasty settings, PFR cementation should be advocated in cases of impaired bone quality.
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http://dx.doi.org/10.1007/s00264-021-05080-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514345PMC
October 2021

Quality and readability of online resources on chronic ankle instability.

Foot Ankle Surg 2021 May 19. Epub 2021 May 19.

Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, Austria. Electronic address:

Background: Online resources on medical conditions often provide misleading or outdated information for patients. The aim of this study was to evaluate the quality of online patient information on ankle instability.

Methods: The terms "ankle instability", "ankle instability treatment" and "ankle laxity" were entered into the three largest internet search engines. The quality, accuracy and readability were evaluated using the EQIP36, a custom 25-item list and the Flesch-Kincaid-Score.

Results: The mean 25-item score of 102 included websites reached 10 ± 5, the mean EQIP36 score was 41 ± 11 and 96% of evaluated websites exceeded the recommended 8th-grade reading level for patient information. The quality was significantly higher with reading levels of college graduates (P < 0.001).

Conclusions: Online resources on ankle instability are often inaccurate or at inappropriately high reading level. The quality and accuracy depend on the reading levels, with high reading levels providing more in-depth information. Foot and ankle surgeons should be aware of available online resources to direct patients to adequate websites.

Level Of Evidence: Level V.
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http://dx.doi.org/10.1016/j.fas.2021.05.003DOI Listing
May 2021

Specific knowledge and resilience affect short-term outcome in patients following primary total hip arthroplasty.

Arch Orthop Trauma Surg 2021 Jun 3. Epub 2021 Jun 3.

Sonderkrankenanstalt Zicksee, Otto Pohanka Platz, 7161, Sankt Andrä am Zicksee, Austria.

Purpose: The aim of the present study was to investigate the potential associations between specific knowledge, resilience and patient-reported outcome measures (PROMS) following primary total hip arthroplasty (THA).

Methods: In a cross-sectional prospective study, consecutive patients following primary THA were included at a rehabilitation center. A novel knowledge score and the validated Connor Davidson Resilience Scale (CD-RISC) were utilized to assess patients' specific knowledge and resilience, respectively. Additionally, patients completed a qualitative questionnaire regarding the information they had received. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), as well as the University of California and Los Angeles Score (UCLA) served as primary outcome measures. Stepwise multiple regression analysis was performed to identify potential predictors of outcome.

Results: A total of 103 patients at a mean age of 67.5 years (SD 10.5, 38-88) were included in the analysis at a median of 55.5 days (IQR 43-81) following primary THA. The mean knowledge and resilience scores were 3.8 (SD 1.6, 0-7) and 69.5 (SD 18.5, 0-100), respectively. Forty-seven percent of patients were afraid of harming their prosthesis and these patients had up to 59% worse WOMAC scores (p < 0.001). WOMAC scores on admission to rehabilitation were predicted by resilience and knowledge scores (R = 0.106, p = 0.036). UCLA scores at the time of admission were predicted by knowledge scores (R = 0.078, p = 0.007).

Conclusion: The present study demonstrated that patients with a feeling of uncertainty had an inferior short-term functional outcome following primary THA. Moreover, it could be shown that higher specific knowledge and resilience are associated with a better functional outcome according to validated PROMS. While these findings need to be prospectively validated in future studies, specific patient knowledge and resilience may have a direct impact on the outcome of primary THA.
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http://dx.doi.org/10.1007/s00402-021-03967-0DOI Listing
June 2021

The Vienna morphological Achilles tendon score-VIMATS : Description, reproducibility and initial clinical results.

Wien Klin Wochenschr 2021 Jun 3;133(11-12):560-567. Epub 2021 Jun 3.

High Field MR Centre, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria.

Objective: The purpose was to introduce the Vienna morphological Achilles tendon score (VIMATS), to evaluate its reproducibility and to assess its clinical application.

Methods: In 38 patients a total number of 40 painful ATs and 20 volunteers were examined on a 3T magnetic resonance imaging (MRI) scanner using a standard MRI protocol. In 20 patients clinical scoring according to the Achilles tendon rupture score was available. Two observers independently assessed the thickness, continuity, signal intensity, and associated pathologies of the Achilles tendon (AT) according to the newly created VIMATS. Intraobserver and interobserver agreements were calculated and the clinical application of the VIMATS regarding its potential to differentiate between patients and volunteers was tested.

Results: An analysis of the Intraclass correlation coefficient (ICC) yielded an excellent intraobserver (ICC 0.925) and interobserver agreement (ICC 0.946) for the total VIMAT score. A significant difference in total VIMATS was found between patients (47.6 ± StD 21.1 points) and volunteers (91.5 ± SD 10.9 points; p < 0.01) as well as a moderate correlation between morphological and clinical scoring (Pearson correlation 0.644).

Conclusion: The VIMAT score is the first MRI score for the semiquantitative morphological evaluation of AT injuries and was shown to be an easy, fast and reproducible tool for assessing injuries of the AT.
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http://dx.doi.org/10.1007/s00508-021-01863-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195882PMC
June 2021

Cross-cultural adaption, translation and validation of the Toronto extremity salvage score (TESS) for patients in German-speaking countries.

Wien Klin Wochenschr 2021 Jun 27;133(11-12):536-542. Epub 2021 Apr 27.

Department of Orthopedics and Trauma Surgery, Division of Orthopedics, Medical University of Vienna, Vienna, Austria.

Objective: The preferred treatment for malignant bone and soft tissue tumors is limb salvage surgery; the Toronto extremity salvage score (TESS) is commonly used to measure physical functioning of the affected extremity. The aims of this study were to translate and culturally adapt the German version of the TESS, as well as to explore its convergent reliability, validity and re-test reliability.

Study Design: Patients (n = 50) 32 lower extremity (LE) and 18 upper extremity (UE) were asked to fill out the German TESS two times (t1: clinical visit, t2: regular email) and the SF-36 once.

Methods: The TESS questionnaires were translated from English into German, back translated into English, and culturally adapted. The reliability was assessed with Cronbach's alpha (α). The validity was measured with the SF-36 physical component score and TESS using the Spearman rank correlation coefficient (r). Furthermore, the test-retest reliability was calculated with the intraclass correlation coefficient (ICC).

Results: Internal consistency for both questionnaires was excellent (LE t1: α = 0.924, t2: α = 0.952; UE t1: α = 0.957, t2: α = 0.898). A statistically significant correlation was found between the SF-36 physical component scale and the German TESS (LE r = 0.741, UE r = 0.713). The ICC between baseline (t1) and re-test (t2) was 0.952 and 0.871 for the lower and upper extremities, respectively.

Conclusion: Initial evidence demonstrated that the German TESS is a valid and reliable instrument for use with patients after surgical treatment of malignant bone or soft tissue sarcoma.
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http://dx.doi.org/10.1007/s00508-021-01865-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195924PMC
June 2021

Extra-abdominal desmoid tumor fibromatosis: a multicenter EMSOS study.

BMC Cancer 2021 Apr 20;21(1):437. Epub 2021 Apr 20.

Orthopaedic Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence, Italy.

Background: Extra-abdominal desmoid tumor fibromatosis (DTF) is a rare, locally aggressive soft tissue tumour. The best treatment modality for this patient cohort is still object of debate.

Questions/purpose: This paper aimed to (1) to compare the outcomes of DTF after different treatment modalities, (2) to assess prognostic factors for recurrence following surgical excision, and (3) to assess prognostic factors for progression during observation.

Methods: This was a retrospective multicenter study under the patronage of the European Musculoskeletal Oncology Society (EMSOS). All seven centres involved were tertiary referral centres for soft tissue tumours. Baseline demographic data was collected for all patients as well as data on the diagnosis, tumour characteristics, clinical features, treatment modalities and whether they had any predisposing factors for DTF.

Results: Three hundred eighty-eight patients (240 female, 140 male) with a mean age of 37.6 (±18.8 SD, range: 3-85) were included in the study. Two hundred fifty-seven patients (66%) underwent surgical excision of ADF, 70 patients (18%) were observed without therapy, the residual patients had different conservative treatments. There were no significant differences in terms of tumour recurrence or progression between the different treatment groups. After surgical excision, younger age, recurrent disease and larger tumour size were risk factors for recurrence, while tumours around the shoulder girdle and painful lesions were at risk of progression in the observational group.

Conclusion: Local recurrence rate after surgery was similar to progression rates under observation. Hence, observation in DTF seems to be justified, considering surgery in case of dimensional progression in 2 consecutive controls (3 and 6 months) and in painful lesions, with particular attention to lesions around the shoulder girdle.
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http://dx.doi.org/10.1186/s12885-021-08189-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059004PMC
April 2021

Comparison of the 7th and 8th version of the AJCC classification system for soft tissue sarcomas of extremities and trunk in patients with localised, intermediate or high-grade disease treated at European tertiary sarcoma centres.

Eur J Surg Oncol 2021 08 29;47(8):2182-2188. Epub 2021 Mar 29.

Department of Orthopaedics and Trauma, Medical University of Graz, Auenbruggerplatz 5, 8036, Graz, Austria.

Background: The updated 8th version of the AJCC-staging system for soft tissue sarcomas (STS) has been criticised for omitting tumour depth as category-defining variable and eventually not improving prognostic accuracy in comparison to the 7th version. This study aimed at investigating the prognostic accuracy of both AJCC-versions in STS-patients treated at European tertiary sarcoma centres.

Methods: 1032 patients (mean age: 60.7 ± 16.3 years; 46.0% [n = 475] females; median follow-up: 38.6 months), treated at five tertiary sarcoma centres for localised, intermediate or high-grade STS of extremities and trunk were retrospectively included. Uni- and multivariate Cox-regression models and Harrell's C-indices were calculated to analyse prognostic factors for overall survival (OS) and assess prognostic accuracy.

Results: In univariate analysis, prognostic accuracy for OS was comparable for both AJCC-versions (C-index: 0.620 [8th] vs. 0.614 [7th]). By adding margins, age, gender, and histology to the multivariate models, prognostic accuracy of both versions could be likewise improved (C-index: 0.714 [8th] vs. 0.705 [7th]). Moreover, tumour depth did not significantly contribute to prognostic accuracy of the 8th version's multivariate model (C-index for both models: 0.714). Stratification into four main T-stages based on tumour size only, as implemented in the 8th version, significantly improved prognostic accuracy between each category. However, T-stages as defined in the 7th version had poorer discriminatory power (C-index: 0.625 [8th] vs. 0.582 [7th]).

Conclusion: Both AJCC-versions perform equally well regarding prognostic accuracy. Yet, simplification of the 8 version by omitting tumour depth as T-stage-defining parameter, whilst emphasizing the importance of tumour size, should be considered advantageous.
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http://dx.doi.org/10.1016/j.ejso.2021.03.252DOI Listing
August 2021

Modular megaprostheses in the treatment of periprosthetic fractures of the femur.

Wien Klin Wochenschr 2021 Jun 13;133(11-12):550-559. Epub 2021 Apr 13.

Department of Orthopaedic and Trauma Surgery, Medical University of Vienna, Waehringer Gürtel 18-20, 1090, Vienna, Austria.

Background: Periprosthetic fractures (PPF) of the femur remain challenging, especially in patients with previous multiple revisions. Modular megaprostheses (mMPs) are rarely used in this indication; however, in some cases mMPs seem to be the last chance for limb salvage. We aimed to evaluate the clinical outcome of PPFs of the femur treated by modular mMPs at our institution.

Patients And Methods: In this study 33 patients (27 female; mean age 79 years) with a PPF after total hip or total knee arthroplasty (no tumor indications) were treated using modular proximal (mPFR; n = 12), distal (mDFR; n = 14) or total (mTFR; n = 7) femur replacement. A retrospective evaluation regarding mortality and revision rates was performed. Failures with need for revision were classified.

Results: At a mean follow up of 60 months (range 0-178 months), the total mortality rate as well as total revision rate were both found to be 39%. At 1 year follow-up the mortality rate was highest within the mDFR group, and less revisions were necessary in the mPFR group, however both findings were not significantly. Those patients, who had revision surgery before PPF, were found to have higher revision rate after implantation of mMP. In the mPFR group, dislocation was the most frequent failure, within the mDFR and the mTFR group infection. In one case amputation of the lower limb was necessary.

Conclusion: mMPs represent a valuable option in PPFs of the femur. Infection and dislocation remain the most frequent complications. Prospective clinical studies are required to further define the outcome of mMPs in PPFs of the femur.
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http://dx.doi.org/10.1007/s00508-021-01838-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195977PMC
June 2021

Pseudotumors in Small-Head Metal-on-Metal Total Hip Arthroplasties at a Minimum Follow-Up of 20 Years.

J Arthroplasty 2021 08 10;36(8):2871-2877. Epub 2021 Mar 10.

Division of Orthopedics, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, Austria.

Background: Metal-on-metal (MOM) surfaces in total hip arthroplasty (THA) have been used widely. Serum cobalt and chromium levels have been the standard investigation for follow-up examinations, but magnetic resonance imaging (MRI) with metal artifact reducing sequences has shown good results in detecting pseudotumors. The aim of this study is to survey a significant correlation among MRI findings, serum metal levels, and clinical scores in patients with small-head MOM implants and if serum cobalt and chromium levels are sufficient in detecting patients with pseudotumors in the long-term follow-up.

Methods: At a minimum follow-up of 20 years, 26 patients (29 THAs) of the original 98 patients (105 THAs) included in this study between November 1992 and May 1994 were available for follow-up examination. Clinical scores, serum metal ion levels, and MRIs were obtained.

Results: We found mean serum cobalt levels of 1.87 μg/L (±3.44) and chromium levels of 2.23 μg/L (±2.96) and very good clinical and functional results (mean Harris Hip Score 88.6) in the long-term follow-up. Pseudotumors were detected in MRIs of 21 hips. There were no significant differences between patients with or without pseudotumors regarding serum metal levels and the correlation for clinical outcome scores, demographic data, and cup inclination. The cumulative rate of survival was still at 91.4% at 22.8 years.

Conclusion: This study presents the first published data on small-head MOM hips, comparing metal ion levels, pseudotumors, clinical, and radiological results in a follow-up period of more than 20 years and reveals that serum metal levels are not significantly higher in patients with pseudotumors.

Level Of Evidence: Therapeutic Level III.
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http://dx.doi.org/10.1016/j.arth.2021.03.022DOI Listing
August 2021

Higher patient knowledge and resilience improve the functional outcome of primary total knee arthroplasty.

Wien Klin Wochenschr 2021 Jun 19;133(11-12):543-549. Epub 2021 Mar 19.

Department of Orthopedics and Trauma Surgery, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.

Background: A significant percentage of patients have an unfavorable outcome following primary total knee arthroplasty (TKA). This study aimed to evaluate whether specific knowledge about the implant and resilience can influence the functional outcome following TKA.

Methods: A consecutive series of 163 patients following primary TKA at a mean age of 70 years (SD 9.1 years) were included at a regional rehabilitation center between December 2015 and December 2016. Specific patient knowledge (scale 0-7), Connor Davidson Resilience Scale (CD-RISC), Western Ontario and McMaster Universities (WOMAC) score, University of California and Los Angeles (UCLA) score and constitutional parameters were assessed on admission. Pearson's correlation analysis and stepwise linear regression analysis were performed to investigate associations between knowledge, resilience and functional scores.

Results: The mean overall knowledge score was 3.5 out of 7 and the mean resilience score was 72.9 out of 100. Mean WOMAC and UCLA scores on admission were 23.8 and 5.5, respectively. Stepwise linear regression analysis identified knowledge and age as significant predictors of WOMAC scores (R = 14.3%, p = 0.003). Knowledge and resilience were identified as significant predictors of UCLA scores (R = 13.8%, p = 0.013).

Conclusion: This study highlights the importance of patient-related factors as part of an integral patient care concept in TKA. Although the identified predictors still need to be refined, it could be demonstrated how better patient knowledge might ultimately lead to better functional outcome following TKA. Routinely assessing patients' resilience might be a useful tool to identify patients at risk for low activity levels.

Level Of Evidence: III. Patient-reported outcome study.
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http://dx.doi.org/10.1007/s00508-021-01829-8DOI Listing
June 2021

How Common Are Chronic Residual Limb Pain, Phantom Pain, and Back Pain More Than 20 Years After Lower Limb Amputation for Malignant Tumors?

Clin Orthop Relat Res 2021 09;479(9):2036-2044

Department of Orthopaedic Surgery, Medical University of Vienna, Vienna, Austria.

Background: After major lower limb amputation, persistent pain is common, with up to 85% of patients reporting recurring phantom or residual-limb pain. Although pain management is an important factor of quality of life in patients with lower limb amputations, there are few long-term data regarding the frequency of persistent pain and how it impacts prosthesis use.

Questions/purposes: (1) How prevalent are different types of pain at long-term follow-up after amputation for malignant tumors? (2) What association do different pain types have with daily prosthesis use?

Methods: Between 1961 and 1995, 124 major amputations for malignant tumors were performed at one center in Austria in patients (1) who spoke German and (2) whose surgical date resulted in the possibility of a minimum follow-up time of 20 years at the time of this survey; those patients were considered potentially eligible for this retrospective study. The indications for major amputation were to achieve local tumor control in limbs that the surgeon deemed unsalvageable without amputation. Of those 124 patients, 71% (88) had died, 9% (11) could not be reached, and 3% (4) declined to participate. Thus, 58% (21 of 36) of those living at the time of this study and who underwent lower limb amputation between 1961 and 1993 with a median (range) follow-up duration of 41 years (23 to 55) completed a standardized questionnaire, including an assessment of pain and daily prosthesis use during the year before the survey. Phantom pain, residual limb pain, and back pain were each further subclassified into pain frequency, intensity, and restrictions in activities of daily living (ADL) due to the specific pain form and rated on a 5- (pain frequency) and 10-point (pain intensity, restrictions in ADL) numerical rating scale. Before multivariate regression analysis, daily prosthesis use was correlated with pain parameters using Spearman correlation testing.

Results: Seventeen of 21 patients reported phantom limb and back pain, and 15 patients reported residual limb pain in the past year. Median (range) phantom pain intensity was 7 (1 to 10) points, median residual limb pain intensity was 4 (1 to 9) points, and median back pain intensity was 5 (1 to 10) points. After controlling for relevant confounding variables such as age at amputation, age at survey, and stump length, we found that less intense residual limb pain (defined on a 10-point scale with 1 representing no pain at all and 10 representing extremely strong pain [95% CI 0.3 to 1.0]; r = 0.8; p = 0.003) was associated with greater daily prosthesis use. Higher amputation levels showed a decreased daily prosthesis use compared with patients with lower amputation levels (defined as transfemoral amputation versus knee disarticulation versus transtibial amputation [95% CI 0.3 to 5.1]; r = 0.5; p = 0.03).

Conclusion: Decades after surgery, many patients with lower limb amputations experience pain that restricts them in terms of ADLs and decreases their daily prosthesis use. This information supports the need for regular residual limb inspections and careful prosthesis fitting even at long-term follow-up, as effective prosthesis fitting is a modifiable cause of residual limb pain. Future studies evaluating long-term treatment effects of pain relief surgery and therapeutic alternatives to conservative pain treatments should be performed, as these approaches may help alleviate pain in patients with refractory postamputation pain.

Level Of Evidence: Level IV, therapeutic study.
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http://dx.doi.org/10.1097/CORR.0000000000001725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373555PMC
September 2021

Epiphysiodesis for the treatment of tall stature and leg length discrepancy.

Wien Med Wochenschr 2021 Apr 18;171(5-6):133-141. Epub 2021 Mar 18.

Department of Orthopedics and Trauma Surgery-Division for Orthopedics, Comprehensive Center for Pediatrics, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.

Painful orthopedic conditions associated with extreme tall stature and leg length discrepancy (LLD) include back pain and adopting bad posture. After failure of conservative treatment options, blocking of the growth plates (epiphysiodesis) around the knee emerged as gold standard in patients with tall stature and LLD in the growing skeleton. Surgical planning includes growth prediction and evaluation of bone age. Since growth prediction is associated with a certain potential error, adequate planning and timing of epiphysiodesis are the key for success of the treatment. LLD corrections up to 5 cm can be achieved, and predicted extreme tall stature can be limited. Percutaneous epiphysiodesis techniques are minimally invasive, safe and efficient methods with low complication rates. In general, a multidisciplinary approach should be pursued when treating children and adolescents with tall stature.
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http://dx.doi.org/10.1007/s10354-021-00828-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016792PMC
April 2021

Schwann cell plasticity regulates neuroblastic tumor cell differentiation via epidermal growth factor-like protein 8.

Nat Commun 2021 03 12;12(1):1624. Epub 2021 Mar 12.

St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria.

Adult Schwann cells (SCs) possess an inherent plastic potential. This plasticity allows SCs to acquire repair-specific functions essential for peripheral nerve regeneration. Here, we investigate whether stromal SCs in benign-behaving peripheral neuroblastic tumors adopt a similar cellular state. We profile ganglioneuromas and neuroblastomas, rich and poor in SC stroma, respectively, and peripheral nerves after injury, rich in repair SCs. Indeed, stromal SCs in ganglioneuromas and repair SCs share the expression of nerve repair-associated genes. Neuroblastoma cells, derived from aggressive tumors, respond to primary repair-related SCs and their secretome with increased neuronal differentiation and reduced proliferation. Within the pool of secreted stromal and repair SC factors, we identify EGFL8, a matricellular protein with so far undescribed function, to act as neuritogen and to rewire cellular signaling by activating kinases involved in neurogenesis. In summary, we report that human SCs undergo a similar adaptive response in two patho-physiologically distinct situations, peripheral nerve injury and tumor development.
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http://dx.doi.org/10.1038/s41467-021-21859-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954855PMC
March 2021

Complications, mobility, and quality of life in ankle sarcoma patients.

Bone Joint J 2021 Mar;103-B(3):553-561

Department of Orthopaedics and Trauma Surgery, Medical University of Vienna, Vienna, Austria.

Aims: The aims of the study were to analyze differences in surgical and oncological outcomes, as well as quality of life (QoL) and function in patients with ankle sarcomas undergoing three forms of surgical treatment, minor or major limb salvage surgery (LSS), or amputation.

Methods: A total of 69 patients with ankle sarcomas, treated between 1981 and 2017 at two tumour centres, were retrospectively reviewed (mean age at surgery: 46.3 years (SD 22.0); 31 females (45%)). Among these 69 patients 25 were analyzed prospectively (mean age at latest follow-up: 61.2 years (SD 20.7); 11 females (44%)), and assessed for mobility using the Prosthetic Limb Users Survey of Mobility (PLUS-M; for amputees only), the Toronto Extremity Salvage Score (TESS), and the University of California, Los Angeles (UCLA) Activity Score. Individual QoL was evaluated in these 25 patients using the five-level EuroQol five-dimension (EQ-5D-5L) and Fragebogen zur Lebenszufriedenheit/Questions on Life Satisfaction (FLZ).

Results: Of the total number of patients in the study, 22 (32%) underwent minor LSS and 22 (32%) underwent major LSS; 25 underwent primary amputation (36%). Complications developed in 26 (38%) patients, and were more common in those with major or minor LSS in comparison to amputation (59% vs 36% vs 20%; p = 0.022). A time-dependent trend towards higher complication risk following any LSS was present (relative risk: 0.204; 95% confidence interval (CI) 0.026 to 1.614; p = 0.095). In the prospective cohort, mean TESS was higher following minor LSS in comparison to amputation (91.0 vs 67.3; p = 0.006), while there was no statistically significant difference between major LSS and amputation (81.6 vs 67.3; p = 0.099). There was no difference in mean UCLA (p = 0.334) between the three groups (p = 0.334). None of the items in FLZ or EQ-5D-5L were different between the three groups (all p > 0.05), except for FLZ item "self-relation", being lower in amputees.

Conclusion: Complications are common following LSS for ankle sarcomas. QoL is comparable between patients with LSS or amputation, despite better mobility scores for patients following minor LSS. We conclude that these results allow a decision for amputation to be made more easily in patients particularly where the principles of oncological surgery would otherwise be at risk. Cite this article:  2021;103-B(3):553-561.
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http://dx.doi.org/10.1302/0301-620X.103B3.BJJ-2020-1308.R1DOI Listing
March 2021

N-Glycan profiling of chondrocytes and fibroblast-like synoviocytes: Towards functional glycomics in osteoarthritis.

Proteomics Clin Appl 2021 05 12;15(2-3):e2000057. Epub 2021 Mar 12.

Karl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, Austria.

Purpose: N-Glycan profiling provides an indicator of the cellular potential for functional pairing with tissue lectins. Following the discovery of galectin expression by chondrocytes as a factor in osteoarthritis pathobiology, mapping of N-glycans upon their phenotypic dedifferentiation in culture and in fibroblast-like synoviocytes is a step to better understand glycobiological contributions to disease progression.

Experimental Design: The profiles of cellular N-glycans of human osteoarthritic chondrocytes and fibroblast-like synoviocytes were characterized by mass spectrometry. RT-qPCR experiments determined mRNA levels of 16 glycosyltransferases. Responsiveness of cells to galectins was quantified by measuring the mRNA level for interleukin-1β.

Results: The shift of chondrocytes to a fibroblastic phenotype (dedifferentiation) is associated with changes in N-glycosylation. The N-glycan profile of chondrocytes at passage 4 reflects characteristics of synoviocytes. Galectins-1 and -3 enhance expression of interleukin-1β mRNA in both cell types, most pronounced in primary culture. Presence of interleukin-1β leads to changes in sialylation in synoviocytes that favor galectin binding.

Conclusions And Clinical Relevance: N-Glycosylation reflects phenotypic changes of osteoarthritic cells in vitro. Like chondrocytes, fibroblast-like synoviocytes express N-glycans that are suited to bind galectins, and these proteins serve as inducers of pro-inflammatory markers in these cells. Synoviocytes can thus contribute to disease progression in osteoarthritis in situ.
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http://dx.doi.org/10.1002/prca.202000057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548877PMC
May 2021
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