Multimodal analysis and comparison of stoichiometric and structural characteristics of parosteal and conventional osteosarcoma with massive sclerosis in human bone.

Osteosarcoma (OS) is the most common malignant primary bone tumor in humans and occurs in various subtypes. Tumor formation happens through malignant osteoblasts producing immature bone. In the present paper we studied two different subtypes of osteosarcoma, from one individual with conventional OS with massive sclerosis and one individual with parosteal OS, based on a multimodal approach including small angle x-ray scattering (SAXS), wide angle x-ray diffraction (WAXS), backscattered electron imaging (BEI) and Raman spectroscopy. It was found that both tumors showed reduced mineral particle sizes and degree of orientation of the collagen-mineral composite in the affected areas, alongside with a decreased crystallinity. Distinct differences between the tumor material from the two individuals were found in the degree of mineralization. Further differences were observed in the carbonate to phosphate ratio, which is related to the degree of carbonate substitution in bone mineral and indicative of the turnover rate. The contraction of the c-axis of the bone mineral crystals proved to be a further, very sensitive parameter, potentially indicative of malignancy.

Less Induction Time and Postoperative Pain Using Spinal Anesthesia Versus General Anesthesia With or Without the Use of Peripheral Nerve Blocks in Total Knee Arthroplasty.

BACKGROUND: Our aim was to analyze anesthetic induction time and postoperative pain using spinal anesthesia versus general anesthesia with or without the use of peripheral nerve blocks (PNBs) in total knee arthroplasty. The hypothesis was that spinal anesthesia would be beneficial with respect to induction time and postoperative pain and that PNBs would complement this effect. METHODS: Patients were stratified according to demographics, American Society of Anesthesiologists physical status classification system (ASA), and opioid intake and divided into: (A) general anesthesia without PNB; (B) general anesthesia with PNB; (C) spinal anesthesia without PNB; and (D) spinal anesthesia with PNB. Endpoints were anesthetic induction time, opioid consumption, and pain. Of 559 patients, 348 (62.3%) received general anesthesia (consisting of group A with 46 and group B with 302 patients), and 211 (37.7%) spinal anesthesia (consisting of group C with 117 and group D with 94 patients). RESULTS: We observed significantly lower total opioid intake 48 hours postoperative when applying spinal anesthesia by 2.08 mg (P < .05) of intravenous morphine-equivalent, and a reduction of 7.0 minutes (P < .05) until skin incision. The application of a PNB achieved a reduction of piritramide intake of 3.59 mg (P < .05) 48 hours postoperative and lengthened induction time by 8.5 minutes (P < .05). CONCLUSIONS: Statistically shorter anesthetic induction times without clinical relevance, but lower postoperative opioid dosages with clinical relevance were observed for patients undergoing total knee arthroplasty with spinal anesthesia. The additional application of PNBs led to a lower need for opioids and lower pain levels in the early postoperative phase.

DNA-PKcs Inhibition Sensitizes Human Chondrosarcoma Cells to Carbon Ion Irradiation via Cell Cycle Arrest and Telomere Capping Disruption.

In order to overcome the resistance to radiotherapy in human chondrosarcoma cells, the prevention from efficient DNA repair with a combined treatment with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) inhibitor AZD7648 was explored for carbon ion (C-ion) as well as reference photon (X-ray) irradiation (IR) using gene expression analysis, flow cytometry, protein phosphorylation, and telomere length shortening. Proliferation markers and cell cycle distribution changed significantly after combined treatment, revealing a prominent G2/M arrest. The expression of the G2/M checkpoint genes cyclin B, CDK1, and WEE1 was significantly reduced by IR alone and the combined treatment. While IR alone showed no effects, additional AZD7648 treatment resulted in a dose-dependent reduction in AKT phosphorylation and an increase in Chk2 phosphorylation. Twenty-four hours after IR, the key genes of DNA repair mechanisms were reduced by the combined treatment, which led to impaired DNA repair and increased radiosensitivity. A time-dependent shortening of telomere length was observed in both cell lines after combined treatment with AZD7648 and 8 Gy X-ray/C-ion IR. Our data suggest that the inhibition of DNA-PKcs may increase sensitivity to X-rays and C-ion IR by impairing its functional role in DNA repair mechanisms and telomere end protection.

Long-term clinical and radiological outcome of a cementless titanium-coated total knee arthroplasty system.

INTRODUCTION: To ensure a high-quality standard, it is important to frequently evaluate different prostheses models to avoid prostheses with high failure rates. Thus, the aim of the study was to evaluate the long-term outcome of the uncemented titanium-coated total knee arthroplasty (TKA) system (Advanced Coated System (ACS) III, Implantcast, GERMANY). We hypothesized that the ACS III would have a similar performance as other cemented TKA systems. MATERIALS AND METHODS: A total of 540 ACS III mobile-bearing knee joint prostheses were implanted in 495 patients. The visual analogue scale (VAS) score, Tegner activity score (TAS), knee society score (KSS), Western Ontario and McMaster (WOMAC) score, and the Short Form 12 (SF-12) score for the evaluation of quality of life (QoL) were taken after at least 9 years of follow-up. In addition, we measured range of motion (ROM) and assessed potential sex differences. In addition, the survival analysis was calculated at a median follow-up of 16.7 years. RESULTS: At the final follow-up, 142 patients had died, and 38 had been lost to follow-up. The rate of revision-free implant survival at 16.7 years was 90.0% (95% CI 87.1-92.2%) and the rate of infection-free survival was 97.0% (IQR 95.2-98.2%). The reasons for revision surgery were aseptic loosening (32.9%), followed by infection (27.1%), inlay exchange (15.9%), and periprosthetic fractures (5.7%). At the clinical follow-up visit, the mean VAS score was 1.9 ± 1.9, the median TAS was 3 (IQR 2-4), and the mean KSS for pain and function were 83.5 ± 15.3 and 67.5 ± 25.2, respectively. The mean WOMAC score was 81.1 ± 14.9, and the median SF-12 scores for physical and mental health were 36.9 (IQR 29.8-45.1) and 55.8 (IQR 46.2-61.0), respectively. The mean knee flexion was 102.0° ± 15.4°. Male patients had better clinical outcome scores than female patients [SF-12 mental health score, p = 0.037; SF-12 physical health score, p = 0.032; KSS pain score (p < 0.001), and KSS functional score (p < 0.001)]. CONCLUSION: The ACS III TKA system is a suitable option for the treatment of end-stage osteoarthritis of the knee joint because of its adequate long-term survival. Our findings are in line with published data on similar TKA systems that have shown favourable clinical scores in males. LEVEL OF EVIDENCE: Level III-Retrospective cohort study.

Development of application and surgical technique of total knee arthroplasties: a systematic comparative analysis using worldwide registers.

PURPOSE: The aim was to compare total knee arthroplasty (TKA) between countries with regard to epidemiologic data and surgical technique by the use of worldwide registers and compare findings with a previous report after one decade. METHODS: A systematic search was carried out in November 2022 and compared to previous reports from 2010. We extracted data regarding implanted TKAs, patients' age distribution, procedure types, fixation and revision rates. After identification of 28 national arthroplasty registers, 8of them, namely Australia, Canada, Denmark, England and Wales, New Zealand, Norway, Scotland and Sweden, offered sufficient data and were included in final analysis. RESULTS: A large variation was found in the annual number of implantations per 100,000 inhabitants with a range from 77 to 210.2 (mean 132.8). The fixation type varied strongly as well, e.g. over 95% of totally cemented TKAs in Sweden versus 61.2% cemented fixation in Denmark. Another significant difference was the use of patellar resurfacing in TKA, ranging from 47.3% (Canada) using a patellar button in TKA to less than 5% (Sweden). Within the period of one decade, the mean overall number of annual implantations increased (10%), whilst relative number of revisions decreased, the use of cemented TKA decreased from 87 to 74%, and the use of patella button remained largely inhomogeneous. CONCLUSION: Comparison of arthroplasty registers revealed large differences regarding the annual number of primary TKAs per inhabitant as well as primary TKA procedure types with an increase of annual implantations, decrease of relative number of revisions, and a decrease of the use of cemented systems over the period of one decade.

Occupational injuries in orthopedic and trauma surgeons in Austria.

BACKGROUND: The aim of this study was to investigate the frequency and type of injuries during the career of orthopedic and trauma surgeons in Austria. The hypothesis was that the percentage of occupational injuries among orthopedic and trauma surgeons aligns with the incidence reported in the United States, thus indicating the need for a workplace prevention program. METHODS: A web-based survey was created to collect all necessary data and was sent to all orthopedic and trauma surgeons in Austria via e-mail. Relevant parameters included the surgeons' age, work experience, severity of pain, type of injury, and current pain. Descriptive and explorative statistical analysis was performed. RESULTS: A web-based survey was sent to 1122 board-certified orthopedic surgeons and residents in Austria via e-mail. In total, the response rate was 135 (12%). Seventy-two surgeons (54%) had suffered from one or more occupational injuries during their career. We detected a significant raise of occupational injuries related to the work life duration in which operations were performed and the prevalence of injuries. Most injuries of surgeons were reported between 21 and 30 years of their professional life. According to the frequency at different locations, the distribution in descending order was 25% with injuries of the hand, 22% of finger(s), 12% of the foot, 10% of the spine, 2% of the neck, 3% of the head, and 2% of the abdomen. A causality of incapacity to work through injuries at the workplace was given as 4%. Four percent stated a sick leave of at least 3 weeks. In 7% of the facilities, there was no optimization of preventive measures following an occupational injury. We found no correlation of injuries and resident status. CONCLUSION: Orthopedic surgeons in Austria show a high incidence of occupational injuries in line with the findings of colleagues from the United States. The impact on the health system consists of absenteeism in the workplace of highly specialized health service providers as well as the incapacity to work of a high quality, highly trained workforce of at least 4%. With more preventive measures and more attention and care in the rehabilitation phase after such injuries, a positive effect could be achieved. We believe that residents should be specifically trained on how to avoid such injuries.

Septic complications are on the rise and aseptic loosening has decreased in total joint arthroplasty: an updated complication based analysis using worldwide arthroplasty registers.

INTRODUCTION: A decade ago, a comprehensive study was conducted to investigate the reasons for revision surgeries and their respective frequencies in cases of total hip arthroplasty (THA) and total knee arthroplasty (TKA) based on a complication-based analysis of joint replacement registries. The aim of the present study was to determine whether the causes and risks of their occurrence have changed over the last ten years and to present an updated analysis. MATERIALS AND METHODS: A systematic review of national arthroplasty registries from seven countries examined the causes and rates of revisions of THA and TKA. The study focused on a descriptive analysis that provided an updated overview without statistical significance values. RESULTS: The most common causes for revisions of THA were aseptic loosening (35.1%), deep infection (18.2%), dislocation/instability (15.9%), and periprosthetic fractures (11.4%). The most common causes for revisions of TKA were deep infection (21.6%), aseptic loosening (18.3%), instability (14.1%), and pain (10.9%). CONCLUSION: The findings of this study revealed significant shifts in the underlying causes of revision surgeries in the last decade. Notably, septic complications emerged as the predominant reason for revision of primary TKA, while they also gained prominence as a cause of failure of THA. Although aseptic loosening remains the primary cause for re-operation of THA, the relative risk has decreased for both THA and TKA.

Comparison of revision rates and epidemiological data of a single total knee arthroplasty system of different designs (cruciate retaining, posterior stabilized, mobile bearing, and fixed bearing): a meta-analysis and systematic review of clinical trials and national arthroplasty registries.

BACKGROUND: This study aimed to meta-analyze epidemiological data, revision rates, and incidences of different designs of a single Total Knee Arthroplasty System and compare these factors across different countries. METHODS: A systematic review was conducted on clinical studies and arthroplasty registries of ATTUNE TKA from 1999 to 2020. The main endpoints analyzed were revision rates and epidemiological data. RESULTS: The average age of patients was 67.8 years, with a gender distribution of 60% female and 40% male. The pooled average BMI was 29.4 kg/m2. Eight clinical studies showed a pooled revision rate per 100 observed CY of 0.5 (n = 1343 cases). Cumulative revision rates after 1, 3, and 5 years varied among registries, with the Swiss registry having the highest revision data (after 5 years: 6.3%) and the American registry having the lowest revision data (after 5 years: 1.7%). A comparison of the revision rates of mobile bearing and fixed bearing (41,200 cases) as well as cruciate retaining and posterior stabilized (n = 123,361 cases) showed no significant advantage in the first 5 years after implantation. CONCLUSION: In conclusion, pooled data from 41,200 cases of TKA with a single Total Knee Arthroplasty System in two arthroplasty registries revealed that there was no significant difference in revision rates between the mobile bearing and fixed bearing design within the first 5 years after implantation. In addition, a comparison of the revision rates in n = 123,361 cases showed no significant advantage for cruciate retaining or posterior stabilized in the first 5 years after implantation.

Tenosynovial Giant Cell Tumor Observational Platform Project (TOPP) Registry: A 2-Year Analysis of Patient-Reported Outcomes and Treatment Strategies.

BACKGROUND: The Tenosynovial giant cell tumor Observational Platform Project (TOPP) registry is an international prospective study that -previously described the impact of diffuse-type tenosynovial giant cell tumour (D-TGCT) on patient-reported outcomes (PROs) from a baseline snapshot. This analysis describes the impact of D-TGCT at 2-year follow-up based on treatment strategies. MATERIAL AND METHODS: TOPP was conducted at 12 sites (EU: 10; US: 2). Captured PRO measurements assessed at baseline, 1-year, and 2-year follow-ups were Brief Pain Inventory (BPI), Pain Interference, BPI Pain Severity, Worst Pain, EQ-5D-5L, Worst Stiffness, and -Patient-Reported Outcomes Measurement Information System. Treatment interventions were no current/planned treatment (Off-Treatment) and systemic treatment/surgery (On-Treatment). RESULTS: A total of 176 patients (mean age: 43.5 years) were included in the full analysis set. For patients without active treatment strategy -(Off-Treatment) at baseline (n = 79), BPI Pain Interference (1.00 vs. 2.86) and BPI Pain Severity scores (1.50 vs. 3.00) were numerically favorable in patients remaining Off-Treatment compared with those who switched to an active treatment strategy at year 1. From 1-year to 2-year -follow-ups, patients who remained Off-Treatment had better BPI Pain Interference (0.57 vs. 2.57) and Worst Pain (2.0 vs. 4.5) scores compared with patients who switched to an alternative treatment strategy. In addition, EQ-5D VAS scores (80.0 vs. 65.0) were higher in patients who remained -Off-Treatment between 1-year and 2-year follow-ups compared with patients who changed treatment strategy. For patients receiving systemic treatment at baseline, numerically favorable scores were seen in patients remaining on systemic therapy at 1-year follow-up: BPI Pain Interference (2.79 vs. 5.93), BPI Pain Severity (3.63 vs. 6.38), Worst Pain (4.5 vs. 7.5), and Worst Stiffness (4.0 vs. 7.5). From 1-year to 2-year follow-up, EQ-5D VAS scores (77.5 vs. 65.0) were higher in patients who changed from systemic treatment to a different treatment strategy. CONCLUSION: These findings highlight the impact D-TGCT has on patient quality of life, and how treatment strategies may be influenced by these outcome measures. (ClinicalTrials.gov number: NCT02948088).

More help than harm: surgery for metastatic spinal cord compression is associated with more favorable overall survival within a propensity score analysis.

PURPOSE: Indication for surgical decompression in metastatic spinal cord compression (MSCC) is often based on prognostic scores such as the modified Bauer score (mBs), with favorable prognosis suggestive of surgery and poor prognosis of non-surgical management. This study aimed to clarify if (1) surgery may directly affect overall survival (OS) aside from short-term neurologic outcome, (2) explore whether selected patient subgroups with poor mBs might still benefit from surgery, and (3) gauge putative adverse effects of surgery on short-term oncologic outcomes. METHODS: Single-center propensity score analyses with inverse-probability-of-treatment-weights (IPTW) of OS and short-term neurologic outcomes in MSCC patients treated with or without surgery between 2007 and 2020. RESULTS: Among 398 patients with MSCC, 194 (49%) underwent surgery. During a median follow-up of 5.8 years, 355 patients (89%) died. MBs was the most important predictor for spine surgery (p < 0.0001) and the strongest predictor of favorable OS (p < 0.0001). Surgery was associated with improved OS after accounting for selection bias with the IPTW method (p = 0.021) and emerged as the strongest determinant of short-term neurological improvement (p < 0.0001). Exploratory analyses delineated a subgroup of patients with an mBs of 1 point who still benefited from surgery, and surgery did not result in a higher risk of short-term oncologic disease progression. CONCLUSION: This propensity score analysis corroborates the concept that spine surgery for MSCC associates with more favorable neurological and OS outcomes. Selected patients with poor prognosis might also benefit from surgery, suggesting that even those with low mBs may be considered for this intervention.

Mg-Zn-Ca Alloy (ZX00) Screws Are Resorbed at a Mean of 2.5 Years After Medial Malleolar Fracture Fixation: Follow-up of a First-in-humans Application and Insights From a Sheep Model.

BACKGROUND: In the ongoing development of bioresorbable implants, there has been a particular focus on magnesium (Mg)-based alloys. Several Mg alloys have shown promising properties, including a lean, bioresorbable magnesium-zinc-calcium (Mg-Zn-Ca) alloy designated as ZX00. To our knowledge, this is the first clinically tested Mg-based alloy free from rare-earth elements or other elements. Its use in medial malleolar fractures has allowed for bone healing without requiring surgical removal. It is thus of interest to assess the resorption behavior of this novel bioresorbable implant. QUESTIONS/PURPOSES: (1) What is the behavior of implanted Mg-alloy (ZX00) screws in terms of resorption (implant volume, implant surface, and gas volume) and bone response (histologic evaluation) in a sheep model after 13 months and 25 months? (2) What are the radiographic changes and clinical outcomes, including patient-reported outcome measures, at a mean of 2.5 years after Mg-alloy (ZX00) screw fixation in patients with medial malleolar fractures? METHODS: A sheep model was used to assess 18 Mg-alloy (ZX00) different-length screws (29 mm, 24 mm, and 16 mm) implanted in the tibiae and compared with six titanium-alloy screws. Micro-CT was performed at 13 and 25 months to quantify the implant volume, implant surface, and gas volume at the implant sites, as well as histology at both timepoints. Between July 2018 and October 2019, we treated 20 patients with ZX00 screws for medial malleolar fractures in a first-in-humans study. We considered isolated, bimalleolar, or trimalleolar fractures potentially eligible. Thus, 20 patients were eligible for follow-up. However, 5% (one patient) of patients were excluded from the analysis because of an unplanned surgery for a pre-existing osteochondral lesion of the talus performed 17 months after ZX00 implantation. Additionally, another 5% (one patient) of patients were lost before reaching the minimum study follow-up period. Our required minimum follow-up period was 18 months to ensure sufficient time to observe the outcomes of interest. At this timepoint, 10% (two patients) of patients were either missing or lost to follow-up. The follow-up time was a mean of 2.5 ± 0.6 years and a median of 2.4 years (range 18 to 43 months). RESULTS: In this sheep model, after 13 months, the 29-mm screws (initial volume: 198 ± 1 mm3) degraded by 41% (116 ± 6 mm3, mean difference 82 [95% CI 71 to 92]; p < 0.001), and after 25 months by 65% (69 ± 7 mm3, mean difference 130 [95% CI 117 to 142]; p < 0.001). After 13 months, the 24-mm screws (initial volume: 174 ± 0.2 mm3) degraded by 51% (86 ± 21 mm3, mean difference 88 [95% CI 52 to 123]; p = 0.004), and after 25 months by 72% (49 ± 25 mm3, mean difference 125 [95% CI 83 to 167]; p = 0.003). After 13 months, the 16-mm screws (initial volume: 112 ± 5 mm3) degraded by 57% (49 ± 8 mm3, mean difference 63 [95% CI 50 to 76]; p < 0.001), and after 25 months by 61% (45 ± 10 mm3, mean difference 67 [95% CI 52 to 82]; p < 0.001). Histologic evaluation qualitatively showed ongoing resorption with new bone formation closely connected to the resorbing screw without an inflammatory reaction. In patients treated with Mg-alloy screws after a mean of 2.5 years, the implants were radiographically not visible in 17 of 18 patients and the bone had homogenous texture in 15 of 18 patients. No clinical or patient-reported complications were observed. CONCLUSION: In this sheep model, Mg-alloy (ZX00) screws showed a resorption to one-third of the original volume after 25 months, without eliciting adverse immunologic reactions, supporting biocompatibility during this period. Mg-alloy (ZX00) implants were not detectable on radiographs after a mean of 2.5 years, suggesting full resorption, but further studies are needed to assess environmental changes regarding bone quality at the implantation site after implant resorption. CLINICAL RELEVANCE: The study demonstrated successful healing of medial malleolar fractures using bioresorbable Mg-alloy screws without clinical complications or revision surgery, resulting in pain-free ankle function after 2.5 years. Future prospective studies with larger samples and extended follow-up periods are necessary to comprehensively assess the long-term effectiveness and safety of ZX00 screws, including an exploration of limitations when there is altered bone integrity, such as in those with osteoporosis. Additional use of advanced imaging techniques, such as high-resolution CT, can enhance evaluation accuracy.

Mechanically aligned total knee arthroplasty with the extension-first technique does not equally restore neutral knee alignment in all preoperative knee phenotypes.

PURPOSE: The aim of this study was to determine the change in the long leg axis according to the preoperative knee phenotype using the mechanically aligned extension-first technique in total knee arthroplasty. The hypothesis of this study was that the knee phenotype would have an impact on the postoperative leg axis. METHODS: This was a retrospective comparative study comprising 224 whole-leg radiographs of 112 patients. The leg axes of the pre- and postoperative radiographs were measured and categorized into three preoperative limb phenotypes (based on the hip-knee-ankle angle [HKA]) according to Hirschmann et al. (varus-HKA < 178.5°, neutral-HKA 178.5°-181.5°, and valgus-HKA > 181.5°). Additionally, femoral phenotypes (based on the femoral mechanical angle [FMA], i.e., the mechanical medial distal femoral angle [mMDFA], as well as the tibial phenotypes [based on the tibial mechanical angle, i.e., the medial proximal tibial angle (MPTA)] was calculated. The change in the long leg axis was analyzed and compared with the preoperative limb phenotype. RESULTS: Significantly more patients with preoperative varus alignment shifted to neutral alignment (46.3%, n = 31) than did patients with preoperative valgus alignment (38.9%; n = 14). Moreover, 43.3% of patients (n = 29) with the varus phenotype remained in a varus alignment, compared with the 58.3% of patients with preoperative valgus phenotype (n = 21) remaining in valgus alignment. These findings were similar for both females (p < 0.001) and males (p = 0.015). CONCLUSION: Using an extension-first mechanically aligned surgical technique, varus phenotypes predominantly result in neutral leg axes or remain varus, neutral phenotypes remain neutral, and valgus phenotypes remain valgus or change to neutral phenotypes. This study showed that preoperative knee phenotypes in valgus knees influence this technique more strongly than estimated in previous investigations, which is in line with modern alignment philosophies for TKA. LEVEL OF EVIDENCE: Level IV, retrospective comparative study.

Artificial intelligence-based computer-aided system for knee osteoarthritis assessment increases experienced orthopaedic surgeons' agreement rate and accuracy.

PURPOSE: The aims of this study were to (1) analyze the impact of an artificial intelligence (AI)-based computer system on the accuracy and agreement rate of board-certified orthopaedic surgeons (= senior readers) to detect X-ray features indicative of knee OA in comparison to unaided assessment and (2) compare the results to those of senior residents (= junior readers). METHODS: One hundred and twenty-four unilateral knee X-rays from the OAI study were analyzed regarding Kellgren-Lawrence grade, joint space narrowing (JSN), sclerosis and osteophyte OARSI grade by computerized methods. Images were rated for these parameters by three senior readers using two modalities: plain X-ray (unaided) and X-ray presented alongside reports from a computer-assisted detection system (aided). After exclusion of nine images with incomplete annotation, intraclass correlations between readers were calculated for both modalities among 115 images, and reader performance was compared to ground truth (OAI consensus). Accuracy, sensitivity and specificity were also calculated and the results were compared to those from a previous study on junior readers. RESULTS: With the aided modality, senior reader agreement rates for KL grade (2.0-fold), sclerosis (1.42-fold), JSN (1.37-fold) and osteophyte OARSI grades (3.33-fold) improved significantly. Reader specificity and accuracy increased significantly for all features when using the aided modality compared to the gold standard. On the other hand, sensitivity only increased for OA diagnosis, whereas it decreased (without statistical significance) for all other features. With aided analysis, senior readers reached similar agreement and accuracy rates as junior readers, with both surpassing AI performance. CONCLUSION: The introduction of AI-based computer-aided assessment systems can increase the agreement rate and overall accuracy for knee OA diagnosis among board-certified orthopaedic surgeons. Thus, use of this software may improve the standard of care for knee OA detection and diagnosis in the future. LEVEL OF EVIDENCE: Level II.

Clinical and functional outcome after partial or total claviculectomy without reconstruction for oncologic causes.

BACKGROUND: To achieve clear margins in rare malignant clavicular neoplasms, claviculectomy may become necessary. This study aimed to review clinical, functional, and oncologic outcomes following partial or total claviculectomy without reconstruction. METHODS: This study retrospectively included 15 patients from 2 tertiary sarcoma centers (mean age, 42.6 ± 20.3 years; 66.7% male patients). The median length of clinical and oncologic follow-up was 48.0 months (interquartile range [IQR], 24.0-83.5 months). Functional follow-up (Musculoskeletal Tumor Society score and QuickDASH score [short version of the Disabilities of the Arm, Shoulder and Hand questionnaire]) was available in 9 patients at a median of 36.0 months (IQR, 20.0-100.0 months). RESULTS: Of the 15 patients, 7 underwent total claviculectomy; 5, partial lateral claviculectomy; and 3, partial medial claviculectomy. No postoperative complications emerged. The median Musculoskeletal Tumor Society and QuickDASH scores at latest follow-up amounted to 26.0 points (IQR, 24.0-29.0 points) and 18.0 points (IQR, 11.0-22.0 points), respectively. Notably, scores tended to be lower in patients who underwent total claviculectomy (n = 2) in comparison to partial claviculectomy (n = 7). CONCLUSION: Satisfactory clinical and functional results can be achieved following partial or total claviculectomy without reconstruction, with a low complication rate and acceptable mid- to long-term function.

The Biological Assessment of Shikonin and ß,ß-dimethylacrylshikonin Using a Cellular Myxofibrosarcoma Tumor Heterogeneity Model.

Myxofibrosarcoma (MFS) is a subtype of soft tissue sarcoma of connective tissue, which is characterized by large intra-tumor heterogeneity. Therapy includes surgical resection. Additional chemotherapy is of limited effect. In this study, we demonstrated the potent anticancer activity of shikonin derivatives in our MFS cellular model of tumor heterogeneity for developing a new therapeutic approach. The impact of shikonin and ß,ß-dimethylacrylshikonin (DMAS) on viability, apoptotic induction, MAPK phosphorylation, and DNA damage response were analyzed by means of two human MFS cell lines, MUG-Myx2a and MUG-Myx2b, derived from a singular tumor tissue specimen. MFS cells showed a dose-dependent inhibition of cell viability and a significant induction of apoptosis. Treatment with shikonin derivatives caused an inhibition of pSTAT3 and an increase in pAKT, pERK, pJNK, and pp38. DMAS and shikonin inhibited the activation of the two master upstream regulators of the DNA damage response, ATR and ATM. MUG-Myx2b, which contains an additional PTEN mutation, was more sensitive in some targets. These data demonstrate the significant antitumorigenic effect of shikonin derivatives in MFS and highlight the importance of intra-tumor heterogeneity in treatment planning.

The ATR Inhibitor VE-821 Enhances the Radiosensitivity and Suppresses DNA Repair Mechanisms of Human Chondrosarcoma Cells.

To overcome the resistance to radiotherapy in chondrosarcomas, the prevention of efficient DNA repair with an additional treatment was explored for particle beams as well as reference X-ray irradiation. The combined treatment with DNA repair inhibitors-with a focus on ATRi VE-821-and proton or carbon ions irradiation was investigated regarding cell viability, proliferation, cell cycle distribution, MAPK phosphorylation, and the expression of key DNA repair genes in two human chondrosarcoma cell lines. Pre-treatment with the PARPis Olaparib or Veliparib, the ATMi Ku-55933, and the ATRi VE-821 resulted in a dose-dependent reduction in viability, whereas VE-821 has the most efficient response. Quantification of γH2AX phosphorylation and protein expression of the DNA repair pathways showed a reduced regenerative capacity after irradiation. Furthermore, combined treatment with VE-821 and particle irradiation increased MAPK phosphorylation and the expression of apoptosis markers. At the gene expression and at the protein expression/phosphorylation level, we were able to demonstrate the preservation of DNA damage after combined treatment. The present data showed that the combined treatment with ATMi VE-821 increases the radiosensitivity of human chondrosarcoma cells in vitro and significantly suppresses efficient DNA repair mechanisms, thus improving the efficiency of radiotherapy.

Activation of the Mechanosensitive Ion Channels Piezo1 and TRPV4 in Primary Human Healthy and Osteoarthritic Chondrocytes Exhibits Ion Channel Crosstalk and Modulates Gene Expression.

Osteoarthritis (OA) is the most common degenerative joint disease causing pain and functional limitations. Physical activity as a clinically relevant, effective intervention alleviates pain and promotes joint function. In chondrocytes, perception and transmission of mechanical signals are controlled by mechanosensitive ion channels, whose dysfunction in OA chondrocytes is leading to disease progression. Signaling of mechanosensitive ion channels Piezo/TRPV4 was analyzed by Yoda1/GSK1016790A application and calcium-imaging of Fura-2-loaded chondrocytes. Expression analysis was determined by qPCR and immunofluorescence in healthy vs. OA chondrocytes. Chondrocytes were mechanically stimulated using the Flexcell™ technique. Yoda1 and GSK1016790A caused an increase in intracellular calcium [Ca2+]i for Yoda1, depending on extracellularly available Ca2+. When used concomitantly, the agonist applied first inhibited the effect of subsequent agonist application, indicating mutual interference between Piezo/TRPV4. Yoda1 increased the expression of metalloproteinases, bone-morphogenic protein, and interleukins in healthy and OA chondrocytes to a different extent. Flexcell™-induced changes in the expression of MMPs and ILs differed from changes induced by Yoda1. We conclude that Piezo1/TRPV4 communicate with each other, an interference that may be impaired in OA chondrocytes. It is important to consider that mechanical stimulation may have different effects on OA depending on its intensity.

The use of an individualized intraoperative video shows no impact on the early postoperative clinical outcome after total knee arthroplasty: a prospective, randomized, controlled trial.

PURPOSE: The purpose of the study was to evaluate the potential of an intraoperatively recorded video shown to patients immediately postoperatively on early outcome after total knee arthroplasty (TKA). The hypothesis was that there is a beneficial outcome concerning range of motion (ROM) and patient-reported outcome due to enhanced trust into the artificial joint. METHODS: Seventy-three patients were randomly assigned 1:1 to two study groups in which they were either shown a video of their own postoperative range of motion or they were not. Clinically, the New Knee Society Score (nKSS) and ROM were evaluated and compared between the groups 6 weeks after surgery. Chi-square exact test, Kolmogorov-Smirnov test, Mann-Whitney U test, and the Wilcoxon signed rank test were used. Inter- and intra-class correlations were calculated for measurements of ROM. RESULTS: No clinically relevant differences were observed preoperatively and 6 weeks postoperatively between both groups in range of motion (ROM). All patients were showing a significantly improved clinical outcome 6 weeks after the procedure. Clinical scores showed statistically significant differences with respect to preoperative nKSS for satisfaction and statistically significant differences with respect to postoperative nKSS for function. CONCLUSION: Showing a video filmed immediately after implantation of primary TKA had no significant effect on ROM and clinical outcome at 6 weeks. We believe that face-to-face verbal communication in combination with video-assisted education ensures that patients understand their artificial joint in the best possible way and will continue to use intraoperatively filmed videos to enhance patient engagement during postoperative rehabilitation. LEVEL OF EVIDENCE: I.

Impact of the COVID-19 pandemic on early clinical outcome after total knee arthroplasty: a retrospective comparative analysis.

INTRODUCTION: To help combat the SARS-CoV-2 (COVID-19) pandemic, elective inpatient procedures have been reduced. The authors hypothesized that a nationwide lockdown would negatively affect the postoperative outcome after total knee arthroplasty (TKA) due to reduced physiotherapy as well as restrictions in external facilities of physiotherapy and rehabilitation. MATERIALS AND METHODS: We conducted a retrospective, comparative study including 41 patients who had undergone primary TKA during the first lockdown of the COVID-19 pandemic from March 2020 to April 2020 and a comparable control group consisting of 47 patients with a minimum follow-up of 6 months before the COVID-19 pandemic from 2019. Relevant end points were the visual analogue scale (VAS) for pain, Knee Society Function Score (KSS), Oxford Knee Score (OKS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and range of motion (ROM). RESULTS: The lockdown group had a significantly worse outcome compared to the control group 6 months after TKA regarding WOMAC (p = 0.001), KSS (p < 0.001), OKS (p < 0.001), and length of hospital stay (p < 0.001). We found no statistically significant difference between the groups in ROM (p = 0.132), KSFS (p = 0.933), VAS at rest (p = 0.9.22), and exercise (p = 0.304). CONCLUSION: The COVID-19 pandemic negatively affected early clinical outcome parameters of elective primary TKA at 6 months of follow-up due to restrictions in postoperative care. We believe that standardized protocols for physiotherapy will improve clinical outcomes for TKA in the event of future lockdowns and underline the importance of appropriate postoperative care during this pandemic.

Restoring tibial obliquity for kinematic alignment in total knee arthroplasty: conventional versus patient-specific instrumentation.

INTRODUCTION: In total knee arthroplasty (TKA), tibial obliquity-restoration using kinematic alignment (KA) poses a major difference to conventional mechanical alignment. This study aimed at analysing the accuracy of conventional instrumentation (CI) versus patient-specific instrumentation (PSI) to restore anatomic tibial obliquity measured by the medial proximal tibial angle (MPTA) on conventional X-rays. MATERIALS AND METHODS: One-hundred patients were randomized to receive CI (n = 50) or PSI (n = 50) for TKA. Further 100 patients received CI without randomisation, resulting in 200 patients in total (127 women, mean age: 70.7 (range: 48-90 years). Pre- and postoperative X-rays were measured twice by two observers with a 2-week break in-between. Inter- and intraclass correlations were calculated and postoperative tibial obliquity compared to preoperative anatomy. RESULTS: In 150 patients with CI, no case with tibial obliquity-deviation greater than 2° was found, whilst 21.3% (n = 32) and 0.7% (n = 1) of cases and had a deviation of 0°-1°, and 1°-2°, respectively. In the remaining 78.0% (n = 117), tibial obliquity was restored. In 50 patients with PSI, no single case with a deviation greater than 1° was found. Sixty percent (n = 30) had a deviation of 0°-1°. In the remaining 40.0% (n = 20), no deviation from preoperative measurements was found. Consequently, CI resulted in a significantly smaller change in tibial obliquity from preoperative to postoperative than PSI (p < 0.001). Inter- and intra-class correlations showed a substantial agreement (any ICC > 0.90). CONCLUSION: Both conventional and patient-specific instrumentation revealed adequate results with respect to restoring tibial obliquity in kinematically aligned TKA, with conventional instrumentation achieving superior results.