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Chondrosarcomas, malignant cartilaginous neoplasms, are capable of transitioning to highly aggressive, metastatic, and treatment-refractory states, resulting in significant patient mortality. Here, we aim to uncover the transcriptional program directing such tumor progression in chondrosarcomas. We conduct weighted correlation network analysis to extract a characteristic gene module underlying chondrosarcoma malignancy. Hypoxia-inducible factor-2α (HIF-2α, encoded by EPAS1) is identified as an upstream regulator that governs the malignancy gene module. HIF-2α is upregulated in high-grade chondrosarcoma biopsies and EPAS1 gene amplification is associated with poor prognosis in chondrosarcoma patients. Using tumor xenograft mouse models, we demonstrate that HIF-2α confers chondrosarcomas the capacities required for tumor growth, local invasion, and metastasis. Meanwhile, pharmacological inhibition of HIF-2α, in conjunction with the chemotherapy agents, synergistically enhances chondrosarcoma cell apoptosis and abolishes malignant signatures of chondrosarcoma in mice. We expect that our insights into the pathogenesis of chondrosarcoma will provide guidelines for the development of molecular targeted therapeutics for chondrosarcoma., Chondrosarcomas are frequently aggressive, understanding the transcriptional changes associated with progression may help in developing new treatments. Here, the authors show that HIF-2α is increased in expression on progression and pharmacological inhibition of the protein together with chemotherapy is a useful strategy for controlling tumour growth in mice.

Introduction: The aims of this study were to (1) assess the bone mineral density (BMD) around the knee joint, (2) determine the correlation between central and knee BMDs, and (3) investigate the factors associated with BMD around the knee joint in patients with knee osteoarthritis (OA). Methodology: This cross-sectional study included 122 patients who underwent total knee arthroplasty. Central and knee dual-energy X-ray absorptiometry was performed preoperatively. BMD at 6 regions of interest (ROIs) around the knee joint were measured, and their correlations with central BMD were determined using Spearman's correlation analysis. Lower limb alignment, severity of OA, body mass index (BMI), preoperative functional and pain scores were assessed to elucidate the factors associated with knee BMD using linear regression analysis. Results: Around the knee joint, BMD was the lowest at the distal femoral metaphysis and lateral tibial condyle. Knee BMD was significantly correlated with central BMD. However, the correlation coefficients varied by the ROI. Additionally, multivariate analysis revealed different associations with respect to the regions around the knee joint. Varus alignment of the lower limb was associated with increased BMD of the medial condyles and decreased BMD of lateral condyles. High grade OA was a protective factor; it was associated with increased BMD at the lateral condyles of the femur and tibia. Higher BMI was an independent protective factor in all ROIs around the knee joint except the lateral femoral condyles. Lower functional level was not associated with decreased BMD, whereas a higher pain score was significantly associated with lower BMD at the proximal tibial metaphysis. Conclusions: Knee BMD was significantly correlated with central BMD. However, the correlations varied with the regions around the knee joint probably due to their independent association with the alignment of the lower limb, severity of OA, BMI, and preoperative pain level.

To elucidate the effect of medial meniscus posterior root (MMPR) repair during opening-wedge high tibial osteotomy (OWHTO) in terms of contact pressure (CP) and contact area (CA).Nine fresh-frozen human cadaveric knee specimens were included. Each specimen was tested under 9 conditions comprising 3 different degrees of correction during OWHTO (neutral, 5° of valgus, and 10° of valgus) and 3 different types of MMPR conditions (intact, torn, and repaired). The prepared specimens were attached to a customized tibiofemoral jig in a fully extended state. The CP and CA generated by a tibiofemoral axial load of 650 N was recorded using the Tekscan sensor's pressure mapping software. Statistical analysis was performed using a repeated measures analysis of variance.The increased CP and decreased CA in torn MMPR was decreased and increased, respectively, to the intact MMPR after repairing, irrespective of whether OWHTO was performed. The mean CP at a correction angle of 5° of valgus was 0.4067 ± 0.0768 MPa for intact MMPR, which increased to 0.7340 ± 0.1593 MPa for the torn MMPR and decreased to 0.3614 ± 0.0639 MPa for the repaired MMPR. In addition, the proportion of decrease in CP and increase in CA after MMPR repair was constant, compared with the torn MMPR, irrespective of the degree of correction during OWHTO.MMPR repair decreases CP and increases CA, irrespective of whether OWHTO is performed. The biomechanical advantage of repairing torn MMPR is maintained, regardless of the degree of correction during OWHTO.Both OWHTO and MMPR repair are known to protect the medial compartment of the knee. However, there are concerns in performing 2 procedures simultaneously. Results of our study showed that concurrent repair of the MMPR during OWHTO is useful for protecting the medial compartment of the knee with respect to tibiofemoral contact biomechanics.

The purpose of this study was to analyze the epidemiology of T-score discordance between the spine and femur in the South Korean population and compare the prevalence of T-score discordance between the Korean osteoporosis population and atypical femoral fracture (AFF) patients.A total of 12,422 subjects from the Korea National Health and Nutrition Examination Survey were reviewed retrospectively. T-score discordance was defined as a difference of ≥ 1 standard deviation between the lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD). The prevalence of T-score discordance (low LS [LS BMDFN BMD], low FN [LS BMDFN BMD], and total [low LS + low FN]) was investigated in the osteoporosis and non-osteoporosis groups and stratified by sex and age. T-score discordance of 63 patients with AFFs diagnosed at a single institution was compared with that of the Korean osteoporosis population using propensity score matching.T-score discordance was prevalent in the Korean osteoporosis population (44.8%), and low LS discordance (37.5%) was more frequently seen than low FN discordance (7.2%) (T-score discordance was highly prevalent in the Korean osteoporosis population, and low LS discordance was more common than low FN discordance. Nevertheless, the prevalence of low LS discordance was significantly higher in AFF patients than in the Korean osteoporosis population.

Background With increasing interest in enhanced recovery after surgery (ERAS), the literature on ERAS in orthopedic surgery is also rapidly accumulating. This review article aims to (1) summarize the components of the ERAS protocol applied to orthopedic surgery, (2) evaluate the outcomes of ERAS in orthopedic surgery, and (3) suggest practical strategies to implement the ERAS protocol successfully. Main body Overall, 17 components constituting the highly recommended ERAS protocol in orthopedic surgery were identified. In the preadmission period, preadmission counseling and the optimization of medical conditions were identified. In the preoperative period, avoidance of prolonged fasting, multimodal analgesia, and prevention of postoperative nausea and vomiting were identified. During the intraoperative period, anesthetic protocols, prevention of hypothermia, and fluid management, urinary catheterization, antimicrobial prophylaxis, blood conservation, local infiltration analgesia and local nerve block, and surgical factors were identified. In the postoperative period, early oral nutrition, thromboembolism prophylaxis, early mobilization, and discharge planning were identified. ERAS in orthopedic surgery reduced postoperative complications, hospital stay, and cost, and improved the patient outcomes and satisfaction with accelerated recovery. For successful implementation of the ERAS protocol, various strategies including the standardization of care system, multidisciplinary communication and collaboration, ERAS education, and continuous audit system are necessary. Conclusion The ERAS pathway enhanced patient recovery with a shortened length of stay, reduced postoperative complications, and improved patient outcomes and satisfaction. However, despite the significant progress in ERAS implementation in recent years, it has mainly focused on major surgeries such as arthroplasty. Therefore, further efforts to apply, audit, and optimize ERAS in various orthopedic surgeries are necessary.

BACKGROUND Tranexamic acid (TXA) is typically discontinued on the day of total knee arthroplasty (TKA). However, bleeding may persist for several days. We sought to determine whether sequential administration of intravenous (IV) and oral TXA could reduce hemoglobin (Hb) drop more than IV TXA alone. We also wanted to determine whether the use of additional oral TXA increased the rate of complications of deep vein thrombosis (DVT) or symptomatic pulmonary embolism (PE). METHODS This prospective, randomized controlled trial included 141 patients. We compared the Hb drop, estimated blood loss (EBL), and transfusion rate of patients receiving IV TXA alone (group IV, n = 48) to those of patients who received IV TXA followed by oral TXA for 2 days (group 2D, n = 46) or 5 days (group 5D, n = 47). IV TXA was administered 10 minutes prior to the tourniquet release and 3 hours after the first IV TXA administration. Computed tomography (CT) was performed on postoperative day 6 to identify radiographic evidence of DVT. We also assessed the prevalence of symptomatic DVT and PE. RESULTS There were no differences in maximal Hb drop, Hb drops measured at each time point, EBL, or transfusion rate among the 3 groups. The mean maximal Hb drop was 3.5 g/dL in group IV, 3.2 g/dL in group 2D, and 3.4 g/dL in group 5D. The mean EBL was 999.9 mL in group IV, 886.4 mL in group 2D, and 972.5 mL in group 5D. One patient in each group required a transfusion. There were no differences in the prevalence of radiographic evidence of DVT or symptomatic DVT. Symptomatic DVT occurred in 3 patients in group IV and 2 patients in group 5D. One patient in group IV developed a symptomatic PE. CONCLUSIONS Although there was no increase in the complication rate, the sequential administration of oral TXA for up to 5 days after IV TXA did not decrease Hb drop. Therefore, our findings suggest that sequential use of oral and IV TXA is not recommended. LEVEL OF EVIDENCE Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Background: The anterolateral ligament of the knee (ALL) is a component of the lateral complex that stabilizes the structure against rotational force and may be associated with the outcome of anterior cruciate ligament (ACL) reconstruction (ACLR). Purpose: To (1) find whether the visibility of the structure of the ALL is different in primary and revision ACLR groups, (2) determine whether the abnormal findings of the ALL structure on magnetic resonance imaging (MRI) scans are associated with type of trauma in ACL injury and mode of graft failure, and (3) determine whether there are differences in knee functional scores between patients with or without abnormal findings of the ALL structure on MRI scans in primary and revision ACLR groups. Study Design: Cohort study; Level of evidence, 3. Methods: This retrospective study included 40 patients who underwent primary ACLR and 39 patients who underwent revision ACLR. Conventional MRI (1.5-T) scans taken before primary or revision ACLR were obtained and analyzed for visibility of the ALL, frequency and degree of injury of the ALL, and ALL signal anomalies. We also evaluated 1-year postoperative functional knee scores using the subjective International Knee Documentation Committee and Lysholm scores. Results: Visibility of the ALL was better in the primary ACLR group than the revision ACLR group (38% vs 14%; P = .041). The primary ACLR group showed a lower degree of injury across the femoral, meniscal, and tibial attachment sites than did the revision ACLR group (30% vs 13%, 41% vs 8%, and 62% vs 26%, respectively). Relative signal anomaly of the ALL was more frequent in the case of contact versus noncontact trauma of the ACL (85% vs 15%; P = .035), while absolute signal anomaly was equally observed between cases of contact and noncontact trauma in the primary ACLR group (50% vs 50%). No association was observed between ALL signal anomalies and 1-year postoperative functional knee scores. Conclusion: The revision ACLR group offered less visibility and showed a tendency for more frequent, higher degree of injury to the structure of the ALL. Regardless of observational differences between the 2 groups, no definite relevance was observed between the image and the functional outcome. For the assessment of the ALL, routinely performed conventional MRI alone is insufficient to make a clinical decision.

The viability of augmenting small-diameter hamstring autografts with allografts remains unclear. Recent studies have reported different clinical results after allograft augmentation. Hence, we sought to determine whether hamstring autografts and hybrid grafts differed in terms of failure rates and functional outcomes after anterior cruciate ligament (ACL) reconstruction. We also evaluated whether the results of the comparisons differed based on allograft sterilization methods.This systematic review and meta-analysis were performed by searching the PubMed, Cochrane Library, and EMBASE databases to identify prospective or retrospective studies (evidence levels 1, 2, or 3) that compared the failure rates and functional outcomes of ACL reconstruction using autografts and hybrid grafts.We identified 15 relevant studies, including 1,521 patients, with 798 and 723 treated using autografts and hybrid grafts, respectively. Fourteen studies were retrospective comparative studies, and one was a prospective randomized controlled trial. Of these, three studies used non-irradiated allografts. In the analysis of all participants, no significant differences in failure rates and subjective International Knee Documentation Committee (IKDC) scores were observed between the autograft and hybrid graft groups. Comparing the autograft and hybrid graft groups that used non-irradiated allografts, no differences in the failure rates and subjective IKDC scores were also noted. Meanwhile, in the groups that used irradiated allograft, the autograft group demonstrated higher Lysholm knee scores and reduced anterior laxity than the hybrid graft group.Overall, ACL reconstruction using hybrid grafts may not reduce failure rates compared to reconstructions using hamstring autografts, although hybrid grafts with irradiation may decrease functional outcomes.III; systematic review of level II and III studies.

The purpose of this study aimed to identify the proportion of patients with delayed normalization of C-reactive protein (CRP) and Erythrocyte sedimentation rate (ESR) after TKA, to determine postoperative thresholds predictive of prolonged elevation. Further, we aimed to determine if the clinical outcomes of patients with prolonged elevation were inferior to those without prolonged elevation.The records of 211 unilateral and 320 bilateral TKA were reviewed. Patients were divided into the normal and elevation group based on CRP and ESR levels at 6 weeks and 3 months. The temporal pattern of CRP and ESR change in both groups was compared, and thresholds predictive of elevation at 6 weeks and 3 months were identified. Further, the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and Tegner activity scale of both groups at 6 months, 1 year, and 2 years after TKA were compared.The proportion of patients with elevated CRP and ESR at 6 weeks and 3 months was CRP: 24.2%, 10%, ESR: 51.6%, 29.9% in unilateral and CRP: 31.5%, 10.6%, ESR: 58.1%, 42.7% in bilateral TKA. The thresholds for elevation at 6 weeks and 3 months were 9.5 mg/dL, 11.4 mg/dL (CRP at 6 weeks) and 81.5 mm/h, 74.5 mm/h (ESR at 3 months). There was no difference in the WOMAC score and Tegner activity scale between both groups.CRP and ESR are often elevated for a prolonged period even in the absence of infection after TKA. Such cases show distinct temporal patterns, which are predictable, and do not appear to have a significant effect on clinical outcome.

This study aimed to (1) evaluate the preoperative Hb cut-off value for transfusion after unilateral and bilateral staged (1 week apart) TKAs, respectively, and (2) determine whether cause of preoperative anemia can affect transfusion rate after TKA. A total of 951 patients who underwent TKA (unilateral: 605, bilateral staged: 346) from 2016 to 2019 were reviewed retrospectively. Patient demographics, comorbidities, preoperative Hb level, surgery types, and cause of anemia were evaluated as possible risk factors. The cut-off values for preoperative Hb level to reduce transfusion after TKA were evaluated in each surgery type. Preoperative Hb level, surgery type, and cardiac disease were identified as the risk factors for transfusion after TKA, and preoperative Hb levels of 11.8 (AUC 0.88) and 12.8 (AUC 0.76) were the cut-off values for transfusion after unilateral and staged bilateral TKAs, respectively. Although transfusion rate was higher in anemia with iron deficiency (ID) group than anemia without ID group, preoperative Hb level was also lower in anemia with ID group than anemia without ID group. Single use of preoperative Hb level with different cut-offs depending on the surgery types can be useful indicator for preoperative optimization regardless of cause of anemia.

Studies regarding the best strategy to determine appropriate femoral component rotation during bilateral total knee arthroplasty (TKA) in wind swept deformities (WSD) are very limited. The purpose of this study was (1) to evaluate whether femoral rotational profiles differ between varus and valgus osteoarthritic knees in WSD and (2) to analyze the correlation between femoral rotational profiles and coronal radiologic parameters. A total of 40 patients who were diagnosed with bilateral knee osteoarthritis with WSD between January 2010 and December 2020 at a single institution were retrospectively reviewed. On axial computed tomography scans, femoral rotational profile parameters such as the clinical transepicondylar axis (cTEA) and anterior–posterior (AP) axis were compared between valgus and varus osteoarthritic knees. In standing full-limb AP radiographs, coronal radiographic parameters including hip–knee–ankle angle (HKA), valgus correction angle (VCA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), and joint line convergence angle (JLCA) were measured in both knees. The correlation between the varus-valgus cTEA difference, and differences in coronal radiologic parameters was analyzed. In valgus osteoarthritic knees, cTEA was significantly increased compared to varus osteoarthritic knees by 1.5° (valgus: 7.65° ± 1.82°, varus: 6.15° ± 1.58°, p

Background: We aimed to determine whether temporal values of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) after total knee arthroplasty (TKA) differ between patients with and without elevated preoperative CRP. We hypothesized that temporal pattern of CRP and ESR change would differ between the two groups. Materials and Methods: This retrospective study included 30 TKAs with a diagnosis of osteoarthritis with elevated preoperative CRP (>1 mg/dl) without clinical signs and symptoms of infection before surgery (elevated CRP group). Patients without elevated preoperative CRP were matched in a 1:10 fashion according to age, sex, number of comorbidities and whether TKA was unilateral or bilateral (nonelevated CRP group). The temporal values of CRP and ESR after TKA were compared between the two groups until 2 months after surgery. Results: The mean peak values of CRP and ESR after surgery were similar between the two groups in both unilateral and bilateral TKAs. In the unilateral TKA, mean values of CRP and ESR and the proportions of the knees with normal CRP and ESR at 2 months after surgery were similar in the two groups. However, in the bilateral TKA, mean values of CRP and ESR were higher and the proportions of the knees with normal CRP and ESR at 2 months after surgery were lower in the elevated CRP group compared to the nonelevated CRP group. Conclusions: When performing TKA in patients with elevated preoperative CRP, the fact that the levels of CRP and ESR may not be normalized until 2 months after surgery should be considered during followup.

The role of unicompartmental knee arthroplasty (UKA) in spontaneous osteonecrosis of the knee (SONK) remains controversial, even though SONK involves only one compartment of the knee joint. We aimed to compare the survival rate and clinical outcomes of UKA in SONK and medial compartment osteoarthritis (MOA) via a meta-analysis of previous studies. MEDLINE, Embase, and Cochrane Library were searched up to January 2018 with keywords related to SONK and knee arthroplasty. Studies were selected with predetermined inclusion criteria: (1) medial UKA as the primary procedure, (2) reporting implant survival or clinical outcomes of osteonecrosis and osteoarthritis, and (3) follow-up period > 1 year. Quality assessment was performed using the risk of bias assessment tool for non-randomized studies. A random-effects model was used to estimate the pooled relative risk (RR) and standardized mean difference. The incidence of UKA revision for any reason was significantly higher in SONK than in MOA group (pooled RR = 1.83, p = 0.009). However, the risk of revision due to aseptic loosening was not significantly different between the groups. Moreover, when stratified by the study quality, high-quality studies showed similar risk of overall revision in SONK and MOA (p = 0.71). Subgroup analysis revealed no significant difference in failure between SONK and MOA after cemented mobile and fixed bearing UKA. Results of uncemented UKA were reported only in one study, which showed higher failure of SONK compared to MOA. Clinical outcomes after UKA were similar between SONK and MOA (p = 0.66). Cemented UKA has similar survival and clinical outcomes in SONK and MOA. Prospective studies designed specifically to compare the UKA outcomes in SONK and MOA are necessary.

Background: Studies have reported that opening wedge high tibial osteotomy (OWHTO) without bone grafting has outcomes that are similar to or even better than those of OWHTO with bone grafting, especially after use of a locking plate. However, a consensus on managing the gap after OWHTO has not been established. Purpose: To determine the degree of gap healing achieved without bone grafting, the factors associated with gap healing, and whether additional gap healing would be obtained after plate removal. Study Design: Cohort study; Level of evidence, 3. Methods: This retrospective study included 73 patients who underwent OWHTO without bone grafting between 2015 and 2018. Patients in the study were divided into 2 groups based on the correction angle: small correction group (Results: Although both groups achieved acceptable gap healing regardless of the correction angle, the SC group showed higher and earlier gap healing than did the LC group (gap healing rate 81.4% in the SC group vs 41.7% in the LC group at 3 months postoperatively). The GVR was 8.6% in the SC group and 15.3% in the LC group at 12 months after surgery ( P = .005). Both the amount of time that elapsed after surgery and the correction angle were associated with gap healing ( P < .05). Additional gap healing was observed after plate removal, as the GVR decreased 2.7% more in the patients with plate removal than in patients who did not have plate removal ( P = .012). Conclusion: All patients achieved acceptable gap healing without bone graft. The degree of gap healing was higher in the SC group and increased over time. Gap healing was promoted after plate removal. Considering the results of this study, a bone graft is not necessary in routine OWHTO in terms of gap healing.

Studies regarding the best strategy to determine appropriate femoral component rotation during bilateral total knee arthroplasty (TKA) in wind swept deformities (WSD) are very limited. The purpose of this study was (1) to evaluate whether femoral rotational profiles differ between varus and valgus osteoarthritic knees in WSD and (2) to analyze the correlation between femoral rotational profiles and coronal radiologic parameters.A total of 40 patients who were diagnosed with bilateral knee osteoarthritis with WSD between January 2010 and December 2020 at a single institution were retrospectively reviewed. On axial computed tomography scans, femoral rotational profile parameters such as the clinical transepicondylar axis (cTEA) and anterior-posterior (AP) axis were compared between valgus and varus osteoarthritic knees. In standing full-limb AP radiographs, coronal radiographic parameters including hip-knee-ankle angle (HKA), valgus correction angle (VCA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), and joint line convergence angle (JLCA) were measured in both knees. The correlation between the varus-valgus cTEA difference, and differences in coronal radiologic parameters was analyzed.In valgus osteoarthritic knees, cTEA was significantly increased compared to varus osteoarthritic knees by 1.5° (valgus: 7.65° ± 1.82°, varus: 6.15° ± 1.58°, p 0.001). All coronal radiologic parameters, including HKA, LDFA, MPTA, JLCA, and VCA, were significantly different between valgus and varus knees. In correlation analysis, the varus-valgus cTEA difference was significantly correlated with LDFA (r = 0.365, p = 0.021), MPTA (r = 0.442, p = 0.004), and HKA differences (r = 0.693, p 0.001), with the HKA difference showing the strongest correlation with the cTEA difference.In bilateral knee osteoarthritis with WSD, valgus knees showed significantly increased cTEA compared to varus knees, and the cTEA difference positively correlated with the HKA difference between valgus and varus knees. To determine the optimal femoral component rotation during TKA in WSD, assessment of cTEA with pre-operative CT scans or careful intra-operative measurement is recommended, especially in patients with large HKA difference.III, Retrospective cohort study.

The degree of cartilage degeneration assessed intraoperatively may not be sufficient as a criterion for patellar resurfacing in total knee arthroplasty (TKA). However, single-photon emission tomography/computed tomography (SPECT/CT) is useful for detecting osteoarthritic involvement deeper in the subchondral bone. The purpose of the study was to determine whether SPECT/CT reflected the cartilage lesion underneath the patella in patients with end-stage osteoarthritis (OA) and whether clinical outcomes after TKA without patellar resurfacing differed according to the severity of patellofemoral (PF) OA determined by visual assessment and SPECT/CT findings. This study included 206 knees which underwent TKA. The degree of cartilage degeneration was graded intraoperatively according to the International Cartilage Repair Society grading system. Subjects were classified into low and high uptake groups according to the degree of bone tracer uptake (BTU) on SPECT/CT in the PF joint. The Feller's patella score and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were assessed preoperatively and postoperative 1 and 2 years. The increased BTU in the PF joint was associated with more severe degenerative cartilage changes underneath the patella (p

Introduction Implant material is a more important factor for periprosthetic tibial bone resorption than implant design after total knee arthroplasty (TKA). The virtual perturbation study was planned to perform using single case of proximal tibia model. We determined whether the implant materials’ stiffness affects the degree of periprosthetic tibial bone resorption, and whether the effect of material change with the same implant design differed according to the proximal tibial plateau areas. Materials and methods This three-dimensional finite element analysis included two cobalt-chromium (CoCr) and two titanium (Ti) tibial implants with different designs. They were implanted into the proximal tibial model reconstructed using extracted images from computed tomography. The degree of bone resorption or formation was measured using the strain energy density after applying axial load. The same analysis was performed after exchanging the materials while maintaining the design of each implant. Results The degree of periprosthetic tibial bone resorption was not determined by the type of implant materials alone. When the implant materials were changed from Ti to CoCr, the bone resorption in the medial compartment increased and vice versa. The effect of material composition’s change on anterior and posterior areas varied accordingly. Conclusions Although the degree of bone resorption was associated with implant materials, it differed depending on the design of each implant. The effect on the degree of bone resorption according to the materials after TKA should be evaluated while concomitantly considering design.

Summary Cellular senescence is a complex stress response implicated in aging. Autophagy can suppress senescence but is counterintuitively necessary for full senescence. Although its anti-senescence role is well described, to what extent autophagy contributes to senescence establishment and the underlying mechanisms is poorly understood. Here, we show that selective autophagy of multiple regulatory components coordinates the homeostatic state of senescence. We combined a proteomic analysis of autophagy components with protein stability profiling, identifying autophagy substrate proteins involved in several senescence-related processes. Selective autophagy of KEAP1 promoted redox homeostasis during senescence. Furthermore, selective autophagy limited translational machinery components to ameliorate senescence-associated proteotoxic stress. Lastly, selective autophagy of TNIP1 enhanced senescence-associated inflammation. These selective autophagy networks appear to operate in vivo senescence during human osteoarthritis. Our data highlight a caretaker role of autophagy in the stress support network of senescence through regulated protein stability and unravel the intertwined relationship between two important age-related processes.

Background We determined whether postoperative intravenous (IV) iron supplementation could reduce transfusion rate in patients undergoing staged bilateral total knee arthroplasty (TKA). Furthermore, we examined whether hemoglobin (Hb) levels and iron profile differed between patients with and without postoperative IV iron supplementation. Methods This retrospective, comparative cohort study included 126 patients who underwent primary staged bilateral TKA during a single hospitalization. The second TKA was performed at a week’s interval. Group iron (n = 65) received IV iron immediately after each surgery, while patients in group no-iron (n = 61) received no iron after surgery. Transfusion rate, change in Hb levels, and iron profile including serum iron, ferritin, total iron binding capacity, and transferrin saturation were evaluated preoperatively; on postoperative days 1, 2, and 4 after the first TKA; and postoperative days 1, 2, 4, and 7, 6 weeks, and 3 months after the second TKA. Results There were no significant differences in Hb levels and transfusion rate following staged bilateral TKA between patients with and without postoperative IV iron supplementation although serum iron profiles were improved in patients with IV iron supplementation. Conclusion Postoperative IV iron supplementation immediately after acute blood loss caused by TKA was not effective in improving the transfusion rate. Therefore, surgeons should use protocols other than postoperative IV iron supplementation for reducing the transfusion rate in patients undergoing staged bilateral TKA in a single hospitalization. Level of Evidence III.

IntroductionAt present, information about clinical efficacy and adverse events of controlled release (CR) form of pelubiprofen, a prodrug of 2-arylopropionic acid with relatively selective effects on cyclooxygenase-2 activity, remains scarce. In this study, we sought to determine non-inferiority of pelubiprofen CR 90 mg/day compared to aceclofenac 200 mg/day regarding clinical efficacy and adverse events after a 4-week course of medication in the patients with symptomatic knee osteoarthritis.Materials and methodsA total of 191 patients were randomly assigned to take either pelubiprofen CR 90 mg (n = 95) or aceclofenac 200 mg (n = 96). The primary outcome variable was non-inferiority of pain reduction between baseline and week 4 when assessed using a 100 mm pain visual analogue scale (VAS). Pelubiprofen was considered non-inferior to aceclofenac if the upper limit of the one-sided 97.5% confidence interval for the difference in terms of pain VAS was above 15 mm (the average change of pain VAS in the pelubiprofen group-pain VAS reduction in the aceclofenac group). Secondary outcome variables were the changes in 100 mm pain VAS at week 2 versus baseline, K-Western Ontario, and McMaster University Arthritis Index (K-WOMAC) changes at weeks 2 and 4 as compared to baseline, patient global assessment at weeks 2 and 4. The frequency and amount of rescue medicine usage at weeks 2 and 4 were also evaluated as the secondary outcome variable. For safety analysis, adverse events, clinical laboratory tests, vital signs, and physical examinations were assessed and conducted at each follow-up visit.ResultsAt week 4, the pain VAS values were significantly reduced in both groups receiving either pelubiprofen CR 90 mg or aceclofenac 200 mg as compared to the baseline. However, the pelubiprofen group and the aceclofenac group respectively showed the pain VAS changes of -22 and -21.9 in the pre-protocol set and -20.8 and -21.7 in the full analysis set, confirming non-inferiority. The pelubiprofen CR 90 mg showed a reduced incidence of adverse events compared to the aceclofenac 200 mg (p = 0.005).ConclusionsPelubiprofen CR 90 mg is as effective as aceclofenac 200 mg with reduced adverse events for the treatment of symptomatic knee osteoarthritis.

We aimed at determining whether the coronal alignment of lower extremity was related to rotational geometry of distal femur, femoral anteversion, and tibial torsion in patients with knee osteoarthritis.A total of 422 lower extremities were divided into 3 groups according to the coronal alignment: valgus (n = 31), neutral (n = 78), and varus group (n = 313). Condylar twisting angle was measured to determine rotational geometry of distal femur as the angle between the clinical transepicondylar axis and the posterior condylar line. Femoral anteversion was assessed using the angle between a line intersecting the femoral neck and the posterior condylar line (pFeAV) and the angle between the same line and transepicondylar axis that is not affected by posterior condylar variations (tFeAV). Tibial torsion was evaluated by measuring the angle between the posterior condyles of the proximal tibia and the transmalleolar axis.As the coronal alignment changed from varus to valgus, the condylar twisting angle increased (r = 0.253, P.001; 6.6° in varus, 7.4° in neutral, and 10.2° in valgus group). Although the pFeAV also increased (r = 0.145, P = .003), the tFeAV did not change significantly (P = .218). Mean tFeAV was 4.3° in varus, 4.7° in neutral, and 6.5° in valgus group. In contrast, as the coronal alignment changed from varus to valgus, the external tibial torsion increased (r = 0.374, P.001; 22.6° in varus, 26.3° in neutral, and 32.6° in valgus group).The change patterns of the rotational profiles of the lower extremity according to the coronal alignment should be considered in order to obtain satisfactory rotational alignment after TKA.

Background This study aimed to determine the prevalence of excessive lateral pressure syndrome (ELPS) in potential candidates for high tibial osteotomy (HTO) using single-photon emission computed tomography–computed tomography (SPECT–CT). We also sought to identify risk factors related to the presence of ELPS. Methods This retrospective study included 150 patients (216 knees) who were candidates for HTO from an initial screening of 3579 patients (7158 knees). There were 183 female and 33 male knees with a mean age of 58 years. The presence of ELPS was defined as a grade 3 uptake on the SPECT–CT at the lateral PF joint. To determine the risk factors related to the ELPS, multivariate regression analysis was performed with independent demographic and radiographic variables. Results Increased uptake on the lateral side of the PF joints was detected in 120 knees (56% of total subjects). Of these, 34 (16%) knees presented with a grade 3 uptake, which indicated the presence of ELPS. No single risk factor had significant associations with the presence of ELPS. Conclusions A considerable number of the knees that were candidates for HTO had ELPS. Nonetheless, we did not find any risk factor related to the presence of ELPS. These results suggest that surgeons should be cautious when diagnosing concomitant ELPS despite acceptable radiographic findings from patellofemoral joints when performing HTO.

The purpose of this study is to compare the progression rate of bone union and clinical outcomes of opening wedge high tibial osteotomy (OWHTO) using allogenous bone chip or tri-calcium phosphate (TCP) granule as bone graft materials. The hypothesis was that the bone union progression in OWHTOs using TCP granule grafts would be comparable to that of OWHTOs using allogenous bone chip grafts. Between 2011 and 2013, 54 patients who had undergone OWHTO for genu varum and osteoarthritis were randomized to one of the two groups at five centres. TCP granule was used to fill the defect in 27 patients and lyophilized allogenous bone chip was used in the other 27 patients. The degree of bone union was classified on a five-point scale and evaluated using plain radiographs of the knee at 6 weeks, 3 months, 6 months, and 12 months postoperatively. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, pain Visual Analogue Scale (VAS) score and complications were also evaluated. The highest degree of bone union observed at 6 and 12 months postoperatively was grade 4, and the number of cases of union progression at each time-point was not significantly different between the two groups (p > 0.05). WOMAC and pain VAS scores also showed no differences between the two groups. No complications were observed during the 12-month period following OWHTO in either group. OWHTO using TCP granule bone substitute showed similar bone union rates and clinical outcomes compared to allogenous bone chip grafts. TCP granule can be used as bone substitutes instead of allogenous bone chip grafts in OWHTO. Level 1.

BACKGROUND Some patients with recurrent symptomatic instability after primary anterior cruciate ligament (ACL) reconstruction have an extension deficiency (ED). This study (a) compared preoperative clinical conditions between the ED and non-ED groups undergoing revision ACL reconstruction, (b) documented clinical and arthroscopic findings in ACL-reconstructed patients with reinstability and ED, and (c) determined whether the ED could be resolved and whether the clinical results of revision surgery differed between the ED and non-ED groups. METHODS This study included 58 patients who underwent revision ACL reconstruction. Patients were divided into the ED and non-ED groups. Preoperatively, the demographics and clinical conditions of the two groups were compared. Intraoperatively, the pathological structures that related to ED were documented. After surgery, the degree of postoperative ED and functional outcomes were compared between the two groups at 2-year follow-up. RESULTS The International Knee Documentation Committee subjective score and SF-36 physical component summary scores were worse in the ED group than the non-ED group preoperatively (54 vs 48 [P = 0.014]; 42 vs 39 [P = 0.031], respectively). Intraoperatively, the ED group showed significantly more frequent graft malposition (50% vs 5%), anvil osteophytes (44% vs 0%), and scarring around posterior intercondylar notch (100% vs 0%). However, there was no difference in the degree of postoperative ED and functional outcome between the two groups at follow-up. CONCLUSIONS ED in patients with recurrent instability after primary ACL reconstruction could be treated with good clinical result by addressing the pathological conditions causing ED in addition to ACL re-reconstruction.

Background We sought to document the incidences of deep vein thrombosis (DVT) before and after total knee arthroplasty (TKA). In addition, we aimed to explor whether routine preoperative DVT evaluation was useful to establish DVT treatment strategies after TKA. Finally, we wanted to evaluate whether the incidences of DVT differed between patients undergoing unilateral and staged bilateral TKA within the same hospitalization period. Methods The retrospective study included 153 consecutive patients (253 knees) with osteoarthritis who underwent primary TKA. After surgery, mechanical compression devices (only) were used for DVT prophylaxis. DVT status before and after TKA was determined via 128-row, multidetector, computed tomography/indirect venography. Results Overall, the preoperative DVT incidence was 2.6% per patient and 1.6% per knee. All preoperative DVTs were distal in nature and asymptomatic. After TKA, newly developed thrombi were evident in various calf veins, without propagation of any pre-existing thrombi. Postoperatively, the overall incidences of DVT were 69.9% per patient and 58.5% per knee. The DVT incidences were 66% per patient and 69.8% per knee in the unilateral TKA group. In contrast, the incidences were 72% per patient and 55.5% per knee in the staged bilateral TKA group. There was one case of symptomatic distal (unilateral TKA; 0.65% per patient and 0.4% per knee) and proximal DVT (bilateral TKA; 0.65% per patient and 0.4% per knee), respectively. Conclusions The incidence of symptomatic DVT was low in Asian patients treated with mechanical compression devices alone, although substantial portion of patients had DVT after surgery. Routine preoperative DVT evaluation is probably not necessary; preoperative DVT was rare and of limited clinical relevance. Furthermore, staged bilateral TKA during a single period of hospitalization does not increase the incidence of DVT.

Background We sought to determine the 10-year survivorship of single-radius, posterior-stabilized total knee arthroplasty (TKA) in Asian patients. We also aimed to determine whether the long-term clinical and radiographic results differed between patients with and without patellar resurfacing. Methods This retrospective study included 148 (115 patients) consecutive single-radius, posterior-stabilized TKAs. Ten-year survivorship analysis was performed using the Kaplan–Meier method with additional surgery for any reason as the end-point. Furthermore, long-term clinical and radiographic results of 109 knees (74%; 84 patients) with more than 10-year follow-up were analyzed. Ten-year survivorship and long-term outcomes after surgery were determined, and outcomes were compared between patients with and without patellar resurfacing. Results The cumulative survival rate of the single-radius posterior-stabilized TKA of 148 knees was 97.7% (95% confidence interval, 93.1%–99.3%) at 10 years after surgery. Three knees required additional surgery during the 10-year follow-up because of one case of instability and two cases of periprosthetic infections. Mean postoperative Knee Society knee score and function score were 97 points and 75 points, respectively. There were no cases of aseptic loosening of the prosthesis, even though a non-progressive radiolucent line was found in 10 (9%) knees. There were no differences in postoperative scores and degree of patellar tilt and displacement between patients with and without patellar resurfacing. Conclusions Single-radius, posterior-stabilized TKA showed satisfactory long-term clinical and radiographic outcomes in Asian patients regardless of patellar resurfacing, with comparable survivorship to that reported in westerners.

Background: Although a few studies have reported the incidence of deep vein thrombosis (DVT) after opening-wedge high tibial osteotomy (OWHTO), previous studies focused only on symptomatic DVT. Information is lacking regarding the overall incidence of DVT after OWHTO, thrombus location, and the relationship between DVT and clinical outcome. Purpose: To determine the overall incidence of DVT and classify the location of DVT after OWHTO. We also determined whether significant differences in clinical improvement exist in patients with and without DVT at 6 months and at 2 years after OWHTO. Study Design: Case-control study; Level of evidence, 3. Methods: This study included 46 patients (47 knees) who underwent OWHTO. All patients were instructed to perform knee range of motion exercises and partial weightbearing after drain removal. None of the patients received a chemoprophylaxis for DVT except intermittent pneumatic compression. DVT was diagnosed using 128-row multidetector computed tomography performed before discharge on the fourth postoperative day. The location was classified into 6 segments in the distal portion (muscular and axial veins) and proximal portion (popliteal, femoral, and common femoral veins and veins located above the iliac vein). International Knee Documentation Committee (IKDC) score was assessed preoperatively and postoperatively at 6 months, 1 year, and 2 years using a linear mixed model. Results: Although the incidence of symptomatic DVT was 8.5% (n = 4), the overall incidence of early DVT was 44.7% (n = 21). All DVTs were located in the distal portion of the lower extremity vein, and 76.2% of the DVTs were located in an axial vein. The IKDC scores were 33.6 ± 7.2 and 35.3 ± 9.1 ( P = .910) preoperatively, 38.1 ± 5.6 and 40.6 ± 8.4 ( P = .531) at 6 months after surgery, and 44.8 ± 6.9 and 45.9 ± 11.4 ( P = .786) at 2 years after surgery in patients without and those with DVT, respectively. Conclusion: The overall incidence of early DVT after OWHTO was 44.7%. DVT after OWHTO was found particularly around the osteotomy site (76.2%). Patients with DVT did not have inferior short-term clinical outcomes after surgery.

Background To date, there has been no established protocol regarding the timing of the scheduled administration of antiemetics in total knee arthroplasty (TKA). Previous prospective studies analyzing the scheduled use of antiemetics differed in the timing at which the drugs were administered. However, antiemetic drugs are not administered post-operatively until noxious stimuli caused by drugs used during anesthesia and operative procedures. The purpose of this study was 1) to determine whether preoperative scheduled administration of an antiemetic drug can reduce iatrogenic postoperative nausea and vomiting (PONV) in TKA compared to postoperative administration, and 2) to determine whether there was a difference in postoperative pain, patient satisfaction, and complications after TKA between pre- and postoperative administrations.Methods This retrospective study included patients who were assigned to either intravenous administration of the antiemetic drug (ramosetron) 1 hour before surgery (pre-injection group: 50 patients) or at the end of surgery (post-injection group: 51 patients). The incidence of PONV and the frequency of rescue medicine use were recorded until 48 hours postoperation. Postoperative pain level and satisfaction were also assessed using the visual analogue scale (VAS). Possible complications associated with serotonin receptor antagonists; for example, headaches, dizziness, and drowsiness were also assessed.Results The incidence of nausea events was lower in the pre-injection group than in the post-injection group. However, there was no difference between the two groups in terms of frequency of vomiting events and the use of rescue medicine for PONV. Also, postoperative pain, satisfaction scores, and incidence of complications were not different between the two groups.Conclusions The patients with preoperative scheduled administration of antiemetics showed lower incidence of nausea events than those with postoperative administration. However, it is difficult to conclude that the extent of the effect was clinically significant. Further research is needed to determine the optimal timing and method for more effective antiemetic treatment.

Osteoarthritis (OA) is a prevalent degenerative disease, which involves progressive and irreversible destruction of cartilage matrix. Despite efforts to reconstruct cartilage matrix in osteoarthritic joints, it has been a difficult task as adult cartilage exhibits marginal repair capacity. Here we report the identification of tankyrase as a regulator of the cartilage anabolism axis based on systems-level factor analysis of mouse reference populations. Tankyrase inhibition drives the expression of a cartilage-signature matrisome and elicits a transcriptomic pattern that is inversely correlated with OA progression. Furthermore, tankyrase inhibitors ameliorate surgically induced OA in mice, and stem cell transplantation coupled with tankyrase knockdown results in superior regeneration of cartilage lesions. Mechanistically, the pro-regenerative features of tankyrase inhibition are mainly triggered by uncoupling SOX9 from a poly(ADP-ribosyl)ation (PARylation)-dependent protein degradation pathway. Our findings provide insights into the development of future OA therapies aimed at reconstruction of articular cartilage., Osteoarthritis results from the progressive destruction of cartilage matrix. Here, Kim et al. identify tankyrase as a regulator of cartilage matrix anabolism, and find that tankyrase inhibition, by preventing SOX9 PARylation, protects from cartilage destruction in a mouse model of osteoarthritis.