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Asymmetric tibial insert design is expected to restore normal knee kinematics better than symmetric design. A tri-condylar implant has asymmetric and symmetric tibial inserts with a ball-and-socket joint to replace the post-cam mechanism. The purpose of this study was to compare the knee kinematics of the two designs and to measure tibiofemoral contact stresses, including that of the ball-and-socket joint.Using a computer simulation, the anteroposterior position and axial rotation of the femoral component were simulated during a weight-bearing deep knee bend for six validated models. Contact forces were simultaneously simulated in the medial, lateral, and ball-and-socket compartments. The relative position and the magnitude and direction of each contact force were applied to aforce/displacement control knee simulator. The contact stresses were measured individually using a pressure sensor.The asymmetric tibial insert demonstrated a more posterior position of the femoral component in the lateral compartment during the entire range of motion and greater external rotation of the femoral component, compared to the symmetrical tibial insert. The mean peak contact stress of the medial and lateral compartments was 9 Mpa, with no significant differences between the two designs except at 0°. The contact stress of the ball-and-socket joint was 5 MPa.Asymmetry of the tibial insert shows significant kinematic difference and has little influence on the peak contact stress, which is considerably lower than the yield strength of polyethylene. The asymmetric tibial insert can lead to clinical benefits owing to its kinematic and kinetic properties.

Objectives The concept of locomotive syndrome was proposed to highlight older adults who require nursing care services due to the malfunctioning of their locomotive organs. With the coming of a super-ageing society, there is a growing need to understand the relation between systemic chronic diseases and locomotive syndrome. Methods We analysed the second-visit dataset of the Nagahama Study. The association analysis was performed to identify the chronic diseases that were risk factors associated with the occurrence and the progression of locomotive syndrome in both the cross-sectional and longitudinal studies. Results Hypertension, stroke, coronary heart disease, rheumatoid arthritis, chronic renal failure, osteoporosis, anaemia, and gastroesophageal reflux disease were independently correlated with locomotive syndrome through the deterioration of body pain, social activity, and cognitive function in the cross-sectional study. Multiple chronic diseases had additive effects and significantly increased the risk of locomotive syndrome. In the longitudinal study, osteoporosis and kidney disease were significantly correlated with the worsening of the total GLFS-25 score. Conclusions Locomotive syndrome coexisted with various systemic chronic diseases, especially cardiovascular diseases. Osteoporosis and kidney disease were significantly correlated with the progression of locomotive dysfunction. The management of various chronic diseases may be useful to prevent locomotive syndrome and vice versa.

The purpose of this study was to use the finite element method (FEM) to reproduce fracture lines that reach the lateral tibial plateau during open-wedge high tibial osteotomy (OWHTO) in patients with Type III lateral hinge fracture (LHF). It was hypothesized that the FEM could clarify biomechanical causes of Type III LHF, enabling prevention of adverse complications.This study used the nonlinear FEM to analyze the data of eight knees in eight patients (two males and six females) with Type III LHF among 82 patients who underwent OWHTO, as well as the data of eight individuals with no LHF. To predict the onset of Type III LHF, simulation models were also developed in which posterior osteotomy sufficiency varied from 50% to perfect, the latter defined as osteotomy reaching the hinge point.Real-life instances of Type III LHF caused by insufficient posterior osteotomy were reproduced in all patient-specific FEM models, and these models accurately predicted fracture types and locations. During opening of the osteotomy gap, the fracture line reached the lateral tibial plateau, and extended vertically from the end of the insufficient posterior osteotomy, avoiding the rigid proximal tibiofibular joint. In contrast, sufficient posterior osteotomy resulted in a lack of LHF. Posterior osteotomy extension ≥ 70% of the width of the osteotomy plane was the cut-off value to prevent Type III LHF.Forced opening of insufficient posterior osteotomy was found to be a biomechanical cause of Type III LHF that extended perpendicularly to the lateral tibial plateau, avoiding the proximal tibiofibular joint. The clinical significance of this study is that sufficient posterior osteotomy during OWHTO, defined as at least 70% of the width of the osteotomy plane, can prevent Type III LHF.

Several concepts may be used to restore normal knee kinematics after total knee arthroplasty. One is a kinematically aligned (KA) technique, which restores the native joint line and limb alignment, and the other is the use of a medial pivot knee (MPK) design, with a ball and socket joint in the medial compartment. This study aimed to compare motions, contact forces, and contact stress between mechanically aligned (MA) and KA (medial tilt 3° [KA3] and 5° [KA5]) models in MPK. An MPK design was virtually implanted with MA, KA3, and KA5 in a validated musculoskeletal computer model of a healthy knee, and the simulation of motion and contact forces was implemented. Anteroposterior (AP) positions, mediolateral positions, external rotation angles of the femoral component relative to the tibial insert, and tibiofemoral contact forces were evaluated at different knee flexion angles. Contact stresses on the tibial insert were calculated using finite element analysis. The AP position at the medial compartment was consistent for all models. From 0° to 120°, the femoral component in KA models showed larger posterior movement at the lateral compartment (0.3, 6.8, and 17.7 mm in MA, KA3, and KA5 models, respectively) and larger external rotation (4.2°, 12.0°, and 16.8° in the MA, KA3, and KA5 models, respectively) relative to the tibial component. Concerning the mediolateral position of the femoral component, the KA5 model was positioned more medially. The contact forces at the lateral compartment of all models were larger than those at the medial compartment at >60° of knee flexion. The peak contact stresses on the tibiofemoral joint at 90° and 120° of knee flexion were higher in the KA models. However, the peak contact stresses of the KA models at every flexion angle were

This study evaluated the clinical outcomes of medial open-wedge high tibial osteotomy (MOWHTO) and bone marrow lesion (BML) scores and volumes. The hypotheses were that quantitative BML volume is more associated with clinical outcomes of MOWHTO than qualitative BML evaluations, and pre-operative BML volume is associated with the improvement of clinical outcomes.Patients who underwent MOWHTO were retrospectively enrolled. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was recorded before the initial surgery and at plate removal surgery. Using pre-operative short-time inversion recovery magnetic resonance imaging, BMLs were evaluated using three qualitative scores, reflecting the maximum length, proportion, and intensity of BML. For quantification, BMLs of the femur and tibia were separately defined as lesions with a threshold greater than the mean signal intensity plus two standard deviations, using the corresponding lateral condyles as controls. The association between the KOOS scales and BML scores/volume was evaluated using Spearman's correlation coefficient. Multivariate linear regression analyses for post-operative KOOS scales were performed using the tibial BML volume as one of the four independent variables.The final analysis included 40 MOWHTO cases. Two qualitative BML scores correlated only with pre-operative KOOS sports. Femoral and tibial BML volumes were correlated with post-operative KOOS QOL (ρ = 0.40, p = 0.01) and sports (ρ = 0.36, p = 0.02), respectively. Tibial BML volume was significantly correlated with all five delta KOOS scales (ρ = 0.39-0.51, p = 0.01-0.001), however, femoral BML volume was only correlated with delta KOOS QOL (ρ = 0.41, p = 0.01). In multivariate analyses, tibial BML volume was a significant positive predictor for every post-operative KOOS scale, while post-operative % mechanical axis was also a positive significant variable, except post-operative KOOS pain.Tibial BML volume was positively correlated with one post-operative KOOS scale and all delta KOOS scales. A larger pre-operative tibial BML and appropriate alignment correction were associated with a better post-operative KOOS scales. Pre-operative large BML had no negative influence on post-operative clinical outcomes; hence, surgeons need not hesitate to perform MOWHTO in patients with large BMLs in the medial condyles.Retrospective case series, Level IV.

Objective: This cross-sectional study aimed to explore the differences of the medial and lateral sides of the knee joint and precise radiographic abnormalities in contribution to the knee pain and clinical outcomes. Design: Participants 60 years or older who underwent radiographic evaluation were included. Knee radiography was assessed using grading systems of the Osteoarthritis Research Society International (OARSI) atlas. The Japanese Knee Osteoarthritis Measure (JKOM) was evaluated as clinical outcomes. Serum high-sensitivity C-reactive protein (hsCRP) was used to evaluate systemic inflammation. We divided the participants into normal, medial-, lateral-, and medial & lateral-OA types and compared their JKOM using an analysis of covariance. Furthermore, we analyzed the relationship between the knee pain and stiffness of JKOM and the grading of each radiographic feature using a multiple regression model. Results: Lateral- and medial & lateral-OA groups had a significantly worse symptoms in the total and the pain score, especially in movement subscales, in JKOM score. Lateral-OA groups had higher hsCRP than medial-OA group. Multivariate analysis showed that medial joint space narrowing (JSN), and lateral femoral and tibial osteophytes significantly affected knee pain (adjusted odds ratios: 1.73, 1.28, and 1.55, respectively). The radiographic changes are associated with pain more in JSN in the medial side and osteophytes in the lateral side. Conclusion: Lateral- and medial & lateral-OA groups showed worth symptom. In addition, medial JSN and lateral osteophytes have potent effects on the knee pain.

To investigate whether lower limb arterial calcification (LLAC) quantified using computed tomography (CT) was a risk factor for bilateral severe knee osteoarthritis (OA).This cross-sectional study included patients who were scheduled for surgical treatment of primary varus knee OA. Knee OA was evaluated using the Kellgren-Lawrence (KL) classification, KL grades 3 and 4 were defined as severe OA. The LLAC score in the bilateral whole leg CT was quantitatively measured and categorized into low or high groups based on the median value. A modified Poisson regression model was used to examine the relationship between the categorized LLAC score and the presence of bilateral severe knee OA with adjustment for possible confounders.Of a total of 252 patients examined, multivariable modified Poisson regression analysis showed a significant association between higher LLAC score and the presence of bilateral severe knee OA (adjusted risk ratio = 1.28; 95% confidence interval [CI], 1.12-1.48;LLAC was associated with bilateral severe knee OA, and the LLAC score may be a useful measurement to identify patients at risk of bilateral severe knee OA.

Treatment of implant-associated orthopedic infections remains challenging, partly because antimicrobial treatment is ineffective after a mature biofilm covers the implant surface. Currently, the relative efficacy of systemic mono- and combination standard-of-care (SOC) antibiotic therapies over the course of mature biofilm formation is unknown. Thus, we assessed the effects of cefazoline (CEZ), gentamicin (GM), and vancomycin, with or without rifampin (RFP), on Staphylococcus aureus biofilm formation during the establishment of implant-associated osteomyelitis in a murine tibia model. Quantitative scanning electron microscopy of the implants harvested on Days 0, 3, and 7 revealed that all treatments except CEZ monotherapy significantly reduced biofilm formation when antibiotics started at Day 0 (0.46- to 0.25-fold; p < 0.05). When antibiotics commenced 3 days after the infection, only GM monotherapy significantly inhibited biofilm growth (0.63-fold; p < 0.05), while all antibiotics inhibited biofilm formation in combination with RFP (0.56- to 0.44-fold; p < 0.05). However, no treatment was effective when antibiotics commenced on Day 7. To confirm these findings, we assessed bacterial load via colony-forming unit and histology. The results showed that GM monotherapy and all combination therapies reduced the colony-forming unit in the implant (0.41- to 0.23-fold; p < 0.05); all treatments except CEZ monotherapy reduced the colony-forming unit and staphylococcus abscess communities in the tibiae (0.40- to 0.10-fold; p < 0.05). Collectively, these findings demonstrate that systemic SOC antibiotics can inhibit biofilm formation within 3 days but not after 7 days of infection. The efficacy of SOC monotherapies, CEZ particularly, is very limited. Thus, combination treatment with RFP may be necessary to inhibit implant-associated osteomyelitis.

The primary aim of this study was to evaluate the 3-dimensional morphology of the proximal tibia around the osteotomy plane in open-wedge high tibial osteotomy, focusing on the posterolateral (PL) and posteromedial (PM) tibial condyles, and to clarify the changes in morphologic parameters due to differences in patient characteristics and hinge position. The secondary aim was to examine whether morphologic features were associated with insufficient osteotomy, which increases the risk of lateral hinge fracture (LHF).The PL and PM anteroposterior distance, asymmetry ratio, and discrepancy between PL and PM distances along the tibial osteotomy plane were measured. We investigated changes in the parameters due to differences in patient characteristics and hinge position. Osteotomy configurations and LHFs were evaluated using postoperative computed tomography scans.The 3-dimensional preoperative plans of 117 knees (male, 41 knees; female, 76 knees) were evaluated. PL distances were larger than PM distances in almost all cases. The average asymmetry ratio was 1.35, and the standard deviation was 0.22. Higher hinge position was associated with a larger asymmetry ratio and discrepancy (P.001). The asymmetry ratio and discrepancy were independently positively correlated with male sex (P = .002 and P = .001, respectively) and gentle posterior tibial slope (P.001 and P.001, respectively). Osteotomies with type III LHFs showed lower osteotomy sufficiency than osteotomies without LHFs (P.001).PL tibial condyle protrusion was more pronounced in male patients and those with a high hinge position, and may result in insufficient PL osteotomy, which is a risk factor for type III LHF during open-wedge high tibial osteotomy. The optimal hinge position was located approximately 15 mm and 20 mm distal to the lateral tibial plateau in female and male patients, respectively.IV: retrospective case series.

The correlation between static and dynamic mediolateral (ML) tilts of the joint line in the coronal plane remains unknown after total knee arthroplasty (TKA). The purpose was to evaluate the ML tilt as measured by two-dimensional to three-dimensional registration during stair ascent in TKA patients, and to examine the correlation between the dynamic ML tilt and radiographic measurements of static indices. Thirty-two knees that underwent TKA using the mechanical alignment method were included. Continuous sagittal fluoroscopy was taken from before initial contact (IC) until after the toe-off (TO) phase during the stair ascent. The ML tilt of the tibial component relative to the ground was analyzed in terms of dynamic alignment using image-matching techniques, whereas static alignment was measured using standing long-leg radiographs. The correlation between static and dynamic ML tilts was evaluated. In the fluoroscopic analysis, the joint line was neutral (0.0 degree, standard deviation [SD] = 3.4 degrees) around IC phases, then was tilted valgus (5.5° valgus, SD = 2.6 degrees) in the mid-stance (MS) phase. After the TO phase, the joint line became almost neutral (0.4 degrees valgus, SD = 3.1 degrees). The dynamic ML tilt was significantly more varus during the IC phase and significantly more valgus in MS and TO phases than the static ML tilt (1.4 degrees valgus, SD = 2.0 degrees). No correlation was found between static and dynamic ML tilts in weight-bearing phases. During stair ascent, the static tilt had no correlation with the dynamic tilt in weight-bearing phases despite being in the same range. Static lower limb alignment does not reflect coronal alignment during motion. Further research should be conducted to determine whether the horizontal dynamic ML tilt can improve long-term durability and clinical outcomes after TKA.

Objectives This study aimed to evaluate the changes in knee pain, a dominant cause of physical disability, following the coronavirus disease (COVID-19) pandemic, and to identify factors affecting the changes in knee pain. Methods We analysed the pre- and post-COVID-19 longitudinal data set of the Nagahama Study. Knee pain was assessed using the Knee Society Score (KSS). The estimated KSS from the age and sex using regression model in the pre- and post-COVID-19 data set was compared. Factors including the activity score, educational level, and various impacts of COVID-19 were analysed for correlation analyses with changes in KSS. Results Data collected from 6409 participants showed statistically significant differences in KSS, pre- (mean = 22.0; SD = 4.4) and post-COVID-19 (mean = 19.5; SD = 6.4). Low activity score (p = .008), low educational level (p Conclusion The harmful effects of the COVID-19 pandemic on knee pain were suggested. People should be encouraged to engage in physical activities, such as walking, despite the state of emergency. Furthermore, social support for economically disadvantaged groups may improve healthcare access, preventing the acute exacerbations of knee pain.

Bone infection has received increasing attention in recent years as one of the main outstanding clinical problems in orthopaedic-trauma surgery that has not been successfully addressed. In fact, infection may develop across a spectrum of patient types regardless of the level of perioperative management, including antibiotic prophylaxis. Some of the main unknown factors that may be involved, and the main targets for future intervention, include more accurate and less invasive diagnostic options, more thorough and accurate debridement protocols, and more potent and targeted antimicrobials. The underlying biology dominates the clinical management of bone infections, with features such as biofilm formation, osteolysis and vascularisation being particularly influential. Based on the persistence of this problem, an improved understanding of the basic biology is deemed necessary to enable innovation in the field. Furthermore, from the clinical side, better evidence, documentation and outreach will be required to translate these innovations to the patient. This review presents the findings and progress of the AO Trauma Clinical Priority Program on the topic of bone infection. ispartof: EUROPEAN CELLS & MATERIALS vol:42 pages:312-333 ispartof: location:Switzerland status: accepted

Interleukin-27 is a pleiotropic cytokine whose reported functions during bacterial infections are debated as an area of active research. To address this, we investigated the role of IL-27 signaling during Staphylococcus aureus osteomyelitis. Clinically, we observed elevated serum IL-27 levels (20-fold higher, pS. aureus osteomyelitis compared to uninfected patients undergoing elective total joint replacement. Remarkably, IL-27 serum levels immediately following septic death were 60-fold higher vs. uninfected patients (pS. aureus osteomyelitis, and subsequently suppresses inflammation to prevent cytokine storm and osteolysis during chronic infection. In mice, we observed that systemic IL-27 delivery by a recombinant adeno-associated viral vector (rAAV-IL-27) ameliorates surgical site soft tissue infection and peri-implant bone loss during the establishment of implant-associated S. aureus osteomyelitis. This effect was not observed in IL-27 receptor α knock-out mice, suggesting a direct role of IL-27/IL-27R signaling on immune and bone cell functions. Examination of IL-27-mediated immune responses via transcriptome analyses of infected tibiae demonstrated that IL-27 is a biphasic cytokine with IL-27/IL-27R activating immunostimulatory responses including Th17, IL-2, TLR, and iNOS signaling early, and subsequently suppressing these pathways during chronic infection. Ex vivo confirmation using murine macrophages revealed that IL-27 co-stimulates TLR signaling to increase the production of nitric oxide, and immunomodulatory cytokines such as IL-10, IL-21, IL-31, and TNF-β, but is not a chemokine.Author SummaryStaphylococcus aureus is the most common pathogen in orthopaedic infections, and hard-to-treat (MRSA) strains cause >50% of these infections. Thus, there is an urgent need to develop immunotherapies to treat these life-threatening S. aureus infections. Currently, the role of multifunctional IL-27 on S. aureus osteomyelitis is unknown. In a clinical study, we observed that IL-27 is an important biomarker for identifying S. aureus osteomyelitis patients, and that elevated serum IL-27 levels correlated with adverse clinical outcomes, such as septic death. In our efforts to uncover the underlying mechanisms, we reveal that IL-27 is a biphasic cytokine, activating proinflammatory immune pathways, including Th17 responses, early during acute S. aureus osteomyelitis, and subsequently repressing them during the chronic phase to prevent cytokine storm and bone damage. These results indicate that immune modulation of IL-27/IL-27R signaling could be a viable therapeutic strategy in mitigating S. aureus osteomyelitis.

The use of local antibiotics to treat bone infections has been questioned due to a lack of clinical efficacy and emerging information about Staphylococcus aureus colonization of the osteocyte-lacuno canalicular network (OLCN). Here we propose bisphosphonate-conjugated antibiotics (BCA) using a “target and release” approach to deliver antibiotics to bone infection sites. A fluorescent bisphosphonate probe was used to demonstrate bone surface labeling adjacent to bacteria in a S. aureus infected mouse tibiae model. Bisphosphonate and hydroxybisphosphonate conjugates of sitafloxacin and tedizolid (BCA) were synthesized using hydroxyphenyl and aminophenyl carbamate linkers, respectively. The conjugates were adequately stable in serum. Their cytolytic activity versus parent drug on MSSA and MRSA static biofilms grown on hydroxyapatite discs was established by scanning electron microscopy. Sitafloxacin O-phenyl carbamate BCA was effective in eradicating static biofilm: no colony formation units (CFU) were recovered following treatment with 800 mg/L of either the bisphosphonate or α-hydroxybisphosphonate conjugated drug (p &lt, 0.001). In contrast, the less labile tedizolid N-phenyl carbamate linked BCA had limited efficacy against MSSA, and MRSA. CFU were recovered from all tedizolid BCA treatments. These results demonstrate the feasibility of BCA eradication of S. aureus biofilm on OLCN bone surfaces and support in vivo drug development of a sitafloxacin BCA.

Staphylococcus aureus is prevalent in surgical site infections (SSI) and leads to death in approximately 1% of patients. Phase IIB/III clinical trial results have demonstrated that vaccination against the iron-regulated surface determinant protein B (IsdB) is associated with an increased mortality rate in patients with SSI. Thus, we hypothesized that S. aureus induces nonneutralizing anti-IsdB antibodies, which facilitate bacterial entry into leukocytes to generate “Trojan horse” leukocytes that disseminate the pathogen. Since hemoglobin (Hb) is the primary target of IsdB, and abundant Hb-haptoglobin (Hb-Hp) complexes in bleeding surgical wounds are normally cleared via CD163-mediated endocytosis by macrophages, we investigated this mechanism in vitro and in vivo. Our results demonstrate that active and passive IsdB immunization of mice renders them susceptible to sepsis following SSI. We also found that a multimolecular complex containing S. aureus protein A–anti-IsdB–IsdB–Hb-Hp mediates CD163-dependent bacterial internalization of macrophages in vitro. Moreover, IsdB-immunized CD163–/– mice are resistant to sepsis following S. aureus SSI, as are normal healthy mice given anti-CD163–neutralizing antibodies. These genetic and biologic CD163 deficiencies did not exacerbate local infection. Thus, anti-IsdB antibodies are a risk factor for S. aureus sepsis following SSI, and disruption of the multimolecular complex and/or CD163 blockade may intervene., Antibodies to iron-regulated surface determinant protein B (IsdB) facilitate bacterial entry into leukocytes and are a risk factor for S. aureus sepsis following surgical site infection.

Osteomyelitis is a devastating complication of orthopaedic surgery and commonly caused by Staphylococcus aureus (S. aureus) and Group B Streptococcus (GBS, S. agalactiae). Clinically, S. aureus osteomyelitis is associated with local inflammation, abscesses, aggressive osteolysis, and septic implant loosening. In contrast, S. agalactiae orthopaedic infections generally involve soft tissue, with acute life-threatening vascular spread. While preclinical models that recapitulate the clinical features of S. aureus bone infection have proven useful for research, no animal models of S. agalactiae osteomyelitis exist. Here, we compared the pathology caused by these bacteria in an established murine model of implant-associated osteomyelitis. In vitro scanning electron microscopy and CFU quantification confirmed similar implant inocula for both pathogens (~105 CFU/pin). Assessment of mice at 14 days post-infection demonstrated increased S. aureus virulence, as S. agalactiae infected mice had significantly greater body weight, and fewer CFU on the implant and in bone and adjacent soft tissue (p < 0.05). X-ray, µCT, and histologic analyses showed that S. agalactiae induced significantly less osteolysis and implant loosening, and fewer large TRAP+ osteoclasts than S. aureus without inducing intraosseous abscess formation. Most notably, transmission electron microscopy revealed that although both bacteria are capable of digesting cortical bone, S. agalactiae have a predilection for colonizing blood vessels embedded within cortical bone while S. aureus primarily colonizes the osteocyte lacuno-canalicular network. This study establishes the first quantitative animal model of S. agalactiae osteomyelitis, and demonstrates a vasculotropic mode of S. agalactiae infection, in contrast to the osteotropic behavior of S. aureus osteomyelitis.

Total knee arthroplasty (TKA) for valgus knee osteoarthritis is challenging. Although overcorrection in TKA for valgus knee osteoarthritis is recommended, supportive data based on biomechanics have rarely been reported. The purpose of this study was to elucidate whether coronal rotation of the femoral compartment causes abnormal kinematics with or without medial looseness. Multi- and single-radius posterior-stabilised TKA implants were utilised in a computer simulation. A total of 4 mm of slack were provided in the medial collateral ligament (MCL) with varus or valgus position of the femoral component to simulate the context of valgus knee osteoarthritis. Kinematics during gait and squatting activities were evaluated in each condition. During squatting, medial looseness and valgus replacement caused anterior translation of the medial femoral component in mid-flexion in the multi-radius implant. In the worst condition (7° valgus replacement with MCL looseness), there was rapid anterior translation in the multi-radius implant, and moderate anterior translation in the single-radius implant. Although medial looseness alone did not cause abnormal kinematics during gait, the worst condition exhibited an anterior translation to 4.9 mm in the multi-radius implant. This worst condition also exhibited a marked lift-off of 8.0 and 2.9 mm in the multi- and single-radius implants, respectively. Varus position caused little abnormal kinematics even with MCL looseness. Valgus, not varus position of the femoral component caused abnormal kinematics with MCL looseness. To avoid valgus position, the safety target angle of femoral component would be slight varus rather than neutral in valgus knee OA.

The relationship between postoperative tibiofemoral ligament balance and patient satisfaction in total knee arthroplasty (TKA) has been explored previously. However, the optimal intraoperative medial–lateral ligament balance during knee flexion in terms of postoperative patient satisfaction remains unknown. We evaluated the effect of intraoperative flexion instability on patient satisfaction after TKA. This study consisted of 46 knees with varus osteoarthritis undergoing TKA. Medial–lateral component gaps at 0° knee extension and 90° flexion were measured intraoperatively using a knee balancer. Differences in postoperative patient outcomes at 3 weeks and 1 year were compared between medially tight knees in 90° flexion with a medial component gap of

Nonsurgical treatment such as exercise is the preferred method for management of knee osteoarthritis (OA). A combination of aerobic, muscle strengthening, and flexibility exercises is recommended for older adults. However, effects of the exercise intervention on cartilage metabolism remain unclear. This study used biomarkers to investigate the effects of well-rounded exercise program on cartilage metabolism in 42 women (mean age: 59 years). Participants started a weekly supervised exercise program and continued for 12 weeks. Before and after the program, we measured physical performance on the Timed Up-and-Go Test, 3-Minute Walk Test, and 30-Second Chair Stand Test. We collected serum and urine samples at the start of the program until 24 weeks and measured the concentrations of 4 biomarkers related to type II collagen metabolism: serum cartilage type II procollagen carboxy propeptide (sPIICP), urine C-terminal telopeptide of collagen type II (uCTX-II), urine cleavage of type II collagen by collagenases (uC2C), and serum cartilage oligomeric matrix protein (sCOMP). Participants were divided into pre-OA and OA groups based on X-ray findings. The pre-OA group showed significant increases and decreases in sPIICP and uCTX-II concentrations with improved physical performance, respectively. sCOMP concentrations significantly increased in both groups. The exercise also improved physical performance with no detrimental effect on type II collagen metabolism in the OA group. Thus, well-rounded exercise may not only improve physical capacity but also have beneficial effects on type II collagen metabolism, especially in people without radiological OA.

The aims of this study were to investigate the influence of subchondral bone fragility (SBF) on the progression of the knee osteoarthritis by using a novel rat model, and to examine the preventive effect of parathyroid hormone (PTH) on cartilage degeneration. First, 40 rats were assigned to the following four groups: Sham, SBF, Medial meniscal tear (MMT), and MMT + SBF groups. In SBF and MMT + SBF groups, we induced SBF by microdrilling the subchondral bone. Second, 10 additional rats were randomly assigned to the following two groups: MMT + SBF + saline and MMT + SBF + PTH groups. Osteoarthritic changes in the articular cartilage and subchondral bone were evaluated using safranin-O/fast green staining, matrix metalloproteinase-13 (MMP-13), and type X collagen immunohistochemistry, toluidine blue staining, and micro-CT scanning. The combination of SBF and meniscal tear increased the number of mast cells in the subchondral bone, and led to the abnormal subchondral bone microarchitecture, such as abnormally decreased trabecular number and increased trabecular thickness, compared with meniscal tear alone. Moreover, SBF with meniscal tear enhanced articular cartilage degeneration and increased the expression of MMP-13 and type X collagen, compared with meniscal tear alone. The administration of PTH decreased the number of mast cells in the subchondral bone and improved the microstructural parameters of the subchondral bone, and delayed the progression of articular cartilage degeneration. These results suggest that SBF is one of the factors underlying the osteoarthritis development, especially in knees with traumatic osteoarthritis, and that the administration of PTH is a potential therapeutic treatment for preventing OA progression. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1959-1968, 2018.

Objective The aim of this longitudinal study was to examine the clinical significance of soluble lectin-like oxidized low-density lipoprotein receptor 1 (sLOX-1) in patients with rheumatoid arthritis. Methods We gathered demographic and clinical data for a large rheumatoid arthritis cohort at 3 time points. Blood samples were collected at each time point; the number of samples was 282 cases in 2012, 431 cases in 2013, and 500 cases in 2014. Plasma sLOX-1 was measured by enzyme-linked immunosorbent assay. Correlations between sLOX-1 and clinical data were analyzed. Predictive factors associated with changes in sLOX-1 and rheumatoid factor (RF) were analyzed by multivariate linear regression. Results Plasma sLOX-1 level was significantly correlated with RF titer and other clinical parameters. The longitudinal analyses showed that changes in sLOX-1 were significantly correlated with changes in RF titers and with those at baseline. Multivariate linear regression analysis revealed that changes in RF and baseline RF were predictive factors for changes in sLOX-1. Conversely, the changes in RF were significantly correlated with the changes in sLOX-1 in all years. A stepwise regression analysis showed that the change in sLOX-1 was a predictive factor for the change in RF. Conclusions The change in sLOX-1 has predictive value for assessing the change in RF, indicating the usefulness of sLOX-1 in clinical practice.

Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high. Staphylococcus aureus is responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone. Unfortunately, there is no consensus on clinical classifications of osteomyelitis and the ensuing treatment algorithm. Given the high patient morbidity, mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment. Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including: Staphylococcal abscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network (OLCN) of cortical bone. In contrast, S. aureus intracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis. There have also been major advances in our understanding of the immune proteome against S. aureus, from clinical studies of serum antibodies and media enriched for newly synthesized antibodies (MENSA), which may provide new opportunities for osteomyelitis diagnosis, prognosis, and vaccine development. Finally, novel therapies such as antimicrobial implant coatings and antibiotic impregnated 3D-printed scaffolds represent promising strategies for preventing and managing this devastating disease. Here, we review these recent advances and highlight translational opportunities towards a cure.

Background Osteoarthritis (OA) is known as degenerative arthritis. Knee OA is a common disease among aged population and one of the leading causes of disability. Many modalities are used to evaluate bony abnormalities and joint space narrowing for knee OA. Ultrasound is one of the imaging modalities for evaluating knee joint structures such as cartilage, meniscus, osteophyte and synovium. There are few large-scale studies focused on ultrasound findings of the knee of the elderly in general population. Objectives The aim of our study is to evaluate relationship between clinical and ultrasound findings of the elder population. Methods Two hundred and twenty two participants were recruited from Nagahama residents aged 60 years or older. We evaluated the both knees of participants with ultrasound with a 5MHz transducer. Ultrasound scans were performed and assessed by a standardised protocol of the Outcome Measures in Rheumatoid Arthritis Clinical Trial Guidelines. The symptoms were clinically assessed by using Knee Society Score 2011 (KSS). We statistically examined whether the KSS(symptom) correlated with other clinical parameters and each ultrasonographical findings. Results Participants were 65 men and 137 women with a mean age of 67±5 years old. The mean body mass index (BMI) was 21.8±2.76 kg/m2. The symptom subscale of KSS were significantly associated with age, BMI, knee maximum extension and flexion angle, suprapatellar effusion, medial meniscus protorusion, medial recess synovial hypertorophy, and femoral and tibial medial osteophytes. Multiple regression analysis showed that medial osteophytes was most closely related to the symptom subscale of KSS among the ultrasound findings and demographic data evaluated. Conclusions The present study showed a strong association between the symptoms of the knee and the medial osteophytes in Japanese elder population. References [1] Linaker CH,et al. Clin Rheumatol1999. [2] S. Saarakkala,et al.Osteoarthritis and Cartilage2012. [3] Schmidt WA, et al. Ann Rheum Dis2004. [4] Wakefield RJ, et al. J Rheumatol2005 Disclosure of Interest None declared

The thickness and the grade of the articular cartilages of the knee of 34 patients who underwent total knee arthroplasty were evaluated by ultrasound (US) and by histology. The US grade correlated with the histological grade and the thickness of the articular cartilage measured by US. The thickness measured by US was significantly correlated with that measured by histology for the medial condyle. The US thickness was significantly less than the histological thickness for thicker articular cartilages. US grading and the thickness of the articular cartilages evaluated by US is sufficiently reliable to indicate their histological status.

Objective To determine the factors associated with gait parameters in female patients with rheumatoid arthritis (RA). Methods The gait analysis was performed in a large cohort of RA patients, and three basic gait parameters (step length, cadence and gait speed) were calculated. Clinical and laboratory data were also collected. Factors associated with gait parameters were analyzed using multivariable linear regression in the three models with forced entry. Then, we divided those patients with Health Assessment Questionnaire disability index (HAQ) scores ≤ 0.5 into two groups according to their gait speed that were compared to identify the characteristics of patients with a good HAQ score but poor walking ability. Results A total of 318 female patients were analyzed. Knee extension strength had the strongest positive association with all three gait parameters (P < 0.0001), while methotrexate use was also positively associated with all three gait parameters (step length: P < 0.05, cadence: P < 0.05 in model 1 and 2; P < 0.01 in model 3, gait speed: P < 0.01). The disease activity score was negatively associated with step length and gait speed (step length, gait speed: P < 0.01 in model 1 and 2; P < 0.05 in model 3). 26% of patients with good HAQ scores showed slow gait speed. Patients with good HAQ scores and slow gait speed had higher disease activity scores (P < 0.05) and lower knee extension strength (P < 0.0001) than those with good HAQ scores and normal gait speed. Conclusions High knee extension strength, low disease activity and administration of methotrexate were strongly associated with good walking ability in female patients with RA. And, even if patients showed good HAQ scores, about quarter of those patients had poor walking ability, and they showed higher disease activity, lower knee extension strength, compared to the patients with normal gait speed.

The purpose was to measure the morphology of the proximal tibia at different levels for consideration of tibial tray design and placement. The morphology was analysed in 51 knees at 10, 15, 20, and 25 mm below the centre of the lateral tibial plateau. Surface rotation was measured by fitting an ellipse on the resection surface. The anteroposterior (AP), mediolateral (ML), medial AP (MAP) and lateral AP (LAP) dimensions were also measured. The resection surface showed internal rotation of 22.9° from the 10 mm level to the 25 mm level. More distally, the ML/AP and MAP/LAP ratios showed significant changes. Surgeons should pay attention to morphological changes for patients with gross tibial bone defects in primary and revision total knee arthroplasty.

The aims of this study were to investigate the influence of subchondral bone fragility (SBF) on the progression of the knee osteoarthritis by using a novel rat model, and to examine the preventive effect of parathyroid hormone (PTH) on cartilage degeneration. First, 40 rats were assigned to the following four groups: Sham, SBF, Medial meniscal tear (MMT), and MMT + SBF groups. In SBF and MMT + SBF groups, we induced SBF by microdrilling the subchondral bone. Second, 10 additional rats were randomly assigned to the following two groups: MMT + SBF + saline and MMT + SBF + PTH groups. Osteoarthritic changes in the articular cartilage and subchondral bone were evaluated using safranin-O/fast green staining, matrix metalloproteinase-13 (MMP-13), and type X collagen immunohistochemistry, toluidine blue staining, and micro-CT scanning. The combination of SBF and meniscal tear increased the number of mast cells in the subchondral bone, and led to the abnormal subchondral bone microarchitecture, such as abnormally decreased trabecular number and increased trabecular thickness, compared with meniscal tear alone. Moreover, SBF with meniscal tear enhanced articular cartilage degeneration and increased the expression of MMP-13 and type X collagen, compared with meniscal tear alone. The administration of PTH decreased the number of mast cells in the subchondral bone and improved the microstructural parameters of the subchondral bone, and delayed the progression of articular cartilage degeneration. These results suggest that SBF is one of the factors underlying the osteoarthritis development, especially in knees with traumatic osteoarthritis, and that the administration of PTH is a potential therapeutic treatment for preventing OA progression. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1959-1968, 2018.

Objective: Tumour necrosis factor alpha (TNF-α) plays an important role in rheumatoid arthritis (RA). TNF-α is synthesised as a membrane-anchored precursor and is fully activated by a disintegrin and metalloproteinase 17 (ADAM17)-mediated ectodomain shedding. Nardilysin (NRDC) facilitates ectodomain shedding via activation of ADAM17. This study was undertaken to elucidate the role of NRDC in RA. Methods: NRDC-deficient (Nrdc–/– ) mice and macrophage-specific NRDC-deficient (NrdcdelM ) mice were examined in murine RA models, collagen antibody-induced arthritis (CAIA) and K/BxN serum transfer arthritis (K/BxN STA). We evaluated the effect of gene deletion or silencing of Nrdc on ectodomain shedding of TNF-α in macrophages or monocytes. NRDC concentration in synovial fluid from patients with RA and osteoarthritis (OA) were measured. We also examined whether local gene silencing of Nrdc ameliorated CAIA. Results: CAIA and K/BxN STA were significantly attenuated in Nrdc–/– mice and NrdcdelM mice. Gene deletion or silencing of Nrdc in macrophages or THP-1 cells resulted in the reduction of TNF-α shedding. The level of NRDC is higher in synovial fluid from RA patients compared with that from OA patients. Intra-articular injection of anti-Nrdcsmall interfering RNA ameliorated CAIA. Conclusion: These data indicate that NRDC plays crucial roles in the pathogenesis of autoimmune arthritis and could be a new therapeutic target for RA treatment., 新たな関節リウマチ治療のターゲット分子としてのナルディライジン. 京都大学プレスリリース. 2017-07-11.

Background The number of osteoarthritis (OA) patients is increasing year by year because of the aging society. Especially, knee OA is reported to reduce the health life expectancy. The majority of patients are at the early stage of knee OA and are adapted to conservative treatments such as exercise therapy. A lot of biomarkers for cartilage metabolism were previously reported. However, there are few reports that exercise therapy has an effect on the biomarkers related for cartilage metabolism. Objectives To investigate the effect of an exercise therapy on cartilage metabolism using biomarkers. Methods Thirty-eight females (mean age: 59 years) participated in this study. All participants started a weekly exercise and continued it for twelve weeks. Before and after the exercise program, we measured their physical activities; Timed Up and Go test (TUG) and Three Minutes Walking test (3MW). Since the program started, we have collected serum and urine samples from the participants at the start of the program (0 week), at the end of it (12 weeks) and 12 weeks after it (24 weeks). For the collected samples, we measured the following two anabolic and one catabolic biomarkers; serum cartilage type II procollagen carboxy propeptide (sPIICP), serum cartilage oligomeric matrix protein (sCOMP), urine C-terminal telopeptide of collagen type II (uCTX-II). These biomarkers were measured with the enzyme-linked immunosorbent assay method. Results After the twelve weeks exercise program, both TUG and 3MW were significantly improved ( P P P Conclusions These results suggest that an exercise therapy will improve physical activities and that this therapy could influence both cartilage anabolic and catabolic biomarkers. Disclosure of Interest None declared

The effect, on the spinning tension and false twist torque, of a rotary navel rotating in the same direction as that of the rotor was investigated. Differential equations were derived from the equilibrium of forces acting on the yarn element as it passes over the navel. Then, they were solved numerically based on some considerations on the geometrical position of the yarn. It was found that the navel rotation changes the spinning tension and the false twist torque; and that the angle of yarn direction at the edge of the navel affects their changes as well as the friction coefficient between the navel and the yarn. The results of numerical analysis were supported by experimental evidence. The use of the rotary navel to diminish the exceeding peripheral twist extent (PTE) improved the tenacity, the elongation and the initial modulus of the spun yarn. A navel on which curved-grooves were cut was used by way of trial to change the yarn direction at the edge of the navel. In result, actual reduction in yarn tension was not only observed, as was expected through the numerical analysis, but also brought about a spinning tension lower than the possible least one that had been so far supposed to be attained when friction is absent.