Presoaking Grafts in Vancomycin Does Not Impair Graft-Bone Healing in a Rat Anterior Cruciate Ligament Reconstruction Model.

BACKGROUND: The vancomycin presoaking technique (wherein grafts are treated with a vancomycin solution [VS] for anterior cruciate ligament reconstruction [ACLR]) reduces the infection rate after ACLR. However, the effects of this technique on graft-bone healing have not been fully elucidated. PURPOSE: To investigate the effects of vancomycin presoaking on graft-bone healing in a rat ACLR model. STUDY DESIGN: Controlled laboratory study. METHODS: Long flexor digitorum longus tendons were obtained from 9 Wistar rats, and each was randomly allocated to the normal saline (NS) or VS groups. The grafts were immersed in sterile saline for 30 minutes in the NS group and in a 5-mg/mL VS in the VS group. The presence of time-zero graft bacterial contamination was confirmed, and the grafts were incubated in Fluidised Thioglycollate Broth for 2 weeks. ACLR was performed on the right knees of 65 male Wistar rats using the flexor digitorum longus tendons. Each graft was similarly treated. Biomechanical testing, micro-computed tomography, and histological evaluations were performed 4 and 12 weeks postoperatively. RESULTS: The VS group showed significantly reduced graft contamination at time zero (P = .02). The mean maximum loads to failure were 13.7 ± 8.2 N and 11.6 ± 4.8 N in the NS and VS groups, respectively, at 4 weeks (P = .95); and 23.2 ± 13.2 N and 30.4 ± 18.0 N in the NS and VS groups, respectively, at 12 weeks (P = .35). Regarding micro-computed tomography, the mean bone tunnel volumes were 3.76 ± 0.48 mm3 and 4.40 ± 0.58 mm3 in the NS and VS groups, respectively, at 4 weeks (P = .41); and 3.51 ± 0.38 mm3 and 3.67 ± 0.35 mm3 in the NS and VS groups, respectively, at 12 weeks (P = .54). Histological semiquantitative examination revealed no clear between-group differences at any time point. CONCLUSION: Presoaking grafts in vancomycin in a rat ACLR model demonstrated no discernible adverse effects on short- and midterm biomechanical, radiological, and histological investigations. CLINICAL RELEVANCE: The findings provide guidance for surgeons when considering this technique.

Variations in knee cartilage thickness: Fully automatic three-dimensional analysis of MRIs from five manufacturers.

BACKGROUND: Measurements of knee cartilage thickness derived from MR images are attractive biomarkers for osteoarthritis research. Although some cross-sectional multivendor studies exist, none have employed fully automatic three-dimensional MRI analysis. Our objective was to evaluate the variations in knee cartilage thickness measurements obtained using automated methods and MRI instruments from five different vendors. METHODS: The subjects were 10 healthy volunteers aged 22-60 years. MRI models with 3 Tesla strength from five different companies were used. Cartilage thickness was quantified fully automatically for seven regions. We hypothesized that "the MRI model influences cartilage thickness measurements." Inter-measurement error, defined as the absolute difference between the targeted and median thicknesses determined by the five MRI models, was analyzed using histograms. The factors generating the largest inter-measurement error were also examined. RESULTS: No exceptional trends attributable to a specific instrument model were observed, and the p-value from the Kruskal-Wallis test exceeded 0.05 in all seven regions. Therefore, the study hypothesis was rejected. Of the 350 measurements, the inter-measurement error was ≤0.05 mm in 53 %, ≤0.10 mm in 75 %, and ≤0.20 mm in 95 %. Analysis of the medial tibial cartilage, which had the largest inter-measurement error, revealed mis-extraction of synovial fluid as cartilage. CONCLUSIONS: The choice of MRI model did not influence cartilage thickness measurements. Overall, 95 % of the inter-measurement errors were within 0.20 mm. The greatest error resulted from mis-extracting synovial fluid as cartilage.

Scanning electron microscopy analysis of synovial and adipose mesenchymal stem cells adhering to cartilage.

Introduction: Mesenchymal stem cells (MSCs) are increasingly used for intra-articular injections in the treatment of knee osteoarthritis. The aim of this study was to use scanning electron microscopy (SEM) to compare the morphological characteristics of synovial and adipose MSCs. Methods: Synovium and adipose tissues were concurrently harvested from eight patients with knee osteoarthritis. Suspensions of both synovial and adipose MSCs were examined to identify the presence of microspikes. In addition to this study, the MSC suspensions in four patients were applied to abraded porcine cartilage discs and observed 10 s, 10 min, and 1 h later. Results: The median percentage of cells exhibiting microspikes was 14% for synovial MSC suspensions and 13% for adipose MSC suspensions; this difference was not statistically significant (n = 8). No notable differences were detected in the number of adherent cells or in the proportion of cells displaying microspikes or pseudopodia. Strong correlations were found between the proportion of cells with pseudopodia and the number of attached cells for both synovial (r = 0.92, n = 12) and adipose (r = 0.86, n = 12) MSCs, with no significant difference in the correlation coefficients between the two groups. Conclusion: SEM analysis revealed no obvious differences in morphological characteristics during MSC adhesion to cartilage for either synovial or adipose MSCs.

ARID5B is a negative modulator of IL-6 production in rheumatoid arthritis synovial fibroblasts.

Recent single-cell RNA-sequencing analysis of rheumatoid arthritis (RA) synovial tissues revealed the heterogeneity of RA synovial fibroblasts (SFs) with distinct functions such as high IL-6 production. The molecular mechanisms responsible for high IL-6 production will become a promising drug target of RASFs to treat RA. In this study, we performed siRNA screening of 65 transcription factors (TFs) differentially expressed among RASF subsets to identify TFs involved in IL-6 production. The siRNA screening identified 7 TFs including ARID5B, a RA risk gene, that affected IL-6 production. Both long and short isoforms of ARID5B were expressed and negatively regulated by TNF-α in RASFs. The siRNA knockdown and lentiviral overexpression of long and short isoforms of ARID5B revealed that the long isoform suppressed IL-6 production stimulated with TNF-α. eQTL analysis using 58 SFs demonstrated that RA risk allele, rs10821944, in intron 4 of the ARID5B gene had a trend of eQTL effects to the expression of long isoform of ARID5B in SFs treated with TNF-α. ARID5B was found to be a negative modulator of IL-6 production in RASFs. The RA risk allele of ARID5B intron may cause high IL-6 production, suggesting that ARID5B will become a promising drug target to treat RA.

Real-Time Virtual Sonography-Guided Ossicle Removal in Unresolved Osgood-Schlatter Disease.

Osgood-Schlatter disease (OSD) reduces participation in sports activities for adolescents, and, in unresolved cases of the disease in which daily life or sports activity after skeletal maturity are affected, surgical intervention to remove the ossicle is performed to alleviate symptoms. We present a real-time virtual sonography (RVS)-guided ossicle removal in unresolved OSD. The knee joint angle is set at 20°, which is the same position used in magnetic resonance imaging. A 1.5-cm longitudinal skin incision is made at the medial side of the tuberosity. An ultrasound probe covered with a sterile sleeve is then placed longitudinally at the level of tuberosity. The forceps is inserted to peel the patellar tendon off the posterior side of the ossicle. Then the anterior side of the ossicle is peeled off in both the transverse and longitudinal views. When the ossicle is unstable enough, forceps are used to grasp the ossicle and carefully remove it. RVS can see magnetic resonance imaging information in the surrounding area beyond what can be detected by the ultrasound probe, and RVS enables easy determination of the anatomical position of the ossicle, and removal of the ossicle is achieved with low invasiveness.

Histological and biochemical changes in a rat rotator cuff tear model with or without the subacromial bursa.

The subacromial bursa (SAB) plays an important role in the tendon healing process. Based on previous reports, co-culture of the rotator cuff (RC) and SAB have been shown to increase the tendon-related gene expressions, inflammatory cytokines, and tensile strength. However, the nature of the specific biochemical alterations during the inflammatory and repair phases of tendon healing with or without the SAB remain unknown. Using a full-thickness RC tear rat model, we determined how the presence or absence of the SAB alters the histological characteristics and gene expressions. After 3 and 6 weeks, tissues were collected for histological and real-time quantitative polymerase chain reaction (RT-qPCR) evaluations. Results showed greater cell density at 3 weeks, neovascularization and tendon thickening at 6 weeks with SAB preservation. Immunostaining revealed significant increases in type 3 collagen (COL3) expression at 6 weeks with SAB preservation. The RT-qPCR results showed that SAB preservation induced significant increases in the expression of scleraxis, matrix metalloproteinase-13 (MMP-13), interleukin-1ß (IL-1ß), and inducible nitric oxide synthase (iNOS) at 3 weeks and significant increases in COL3, IL-10, and arginase-1 (Arg-1) at 6 weeks. An RC tear undergoes more appropriate inflammatory and repair phases during the tendon healing process when the SAB is retained.

Operator-derived particles and falling bacteria in biosafety cabinets.

Introduction: To ensure the sterility of cell products that cannot undergo conventional sterilization processes, it is imperative to establish and maintain a clean room environment, regulated through environmental monitoring, including particle counts. Nevertheless, the impact of particles generated by operators as potential contaminants remains uncertain. Thus, in this study, we conducted an accelerated test to assess the correlation between particles generated by operators and airborne bacteria, utilizing biosafety cabinets within a typical laboratory setting. These biosafety cabinets create a controlled environment with air conditioning and high-efficiency particulate air (HEPA) filters, offering fundamental data relevant to cell production. Materials and methods: We conducted a simulation followed by real-time experiments involving human operations to explore the quantity of particles, particle sizes, and the percentage of bacteria within these particles. This investigation focused on conditions with heightened particle generation from operators within a biosafety cabinet. The experiment was conducted on operators wearing textile and non-woven dustless clothing within biosafety cabinets. It entailed tapping the upper arms for a duration of 2 min. Results: Observations under biosafety cabinet-off conditions revealed the presence of various particles and falling bacteria in textile clothing. In contrast, no particles or falling bacteria were detected in operators wearing dustless clothing within biosafety cabinets. Notably, a correlation between 5 µm particles and colony-forming units in textile clothing was identified through this analysis. The ratio of falling bacteria to the total number of particles within the biosafety cabinet was 0.8 ± 0.5 % for textile clothing, while it was significantly lower at 0.04 ± 0.2 % for dustless clothing. Conclusion: This study demonstrated that the number of particles and falling bacteria varied depending on the type of clothing and that quantitative data could be used to identify risks and provide basic data for operator education and evidence-based control methods in aseptic manufacturing areas. Although, this study aims to serve as an accelerated test operating under worst-case conditions, the results need to make sure the study range in general research.

Noninvasive total counting of cultured cells using a home-use scanner with a pattern sheet.

The inherent variability in cell culture techniques hinders their reproducibility. To address this issue, we introduce a comprehensive cell observation device. This new approach enhances the features of existing home-use scanners by implementing a pattern sheet. Compared with fluorescent staining, our method over- or underestimated the cell count by a mere 5%. The proposed technique showcased a strong correlation with conventional methodologies, displaying R2 values of 0.91 and 0.99 compared with the standard chamber and fluorescence methods, respectively. Simulations of microscopic observations indicated the potential to estimate accurately the total cell count using just 20 fields of view. Our proposed cell-counting device offers a straightforward, noninvasive means of measuring the number of cultured cells. By harnessing the power of deep learning, this device ensures data integrity, thereby making it an attractive option for future cell culture research.

Characteristics of the synovial microenvironment and synovial mesenchymal stem cells with hip osteoarthritis of different bone morphologies.

BACKGROUND: Variations in bone morphology in patients with hip osteoarthritis (HOA) can be broadly categorized into three types: atrophic, normotrophic, and hypertrophic. Despite the investigations examining clinical elements, such as bone morphology, pain, and range of motion, our understanding of the pathogenesis of HOA remains limited. Previous studies have suggested that osteophytes typically originate at the interface of the joint cartilage, periosteum, and synovium, potentially implicating synovial mesenchymal stem cells (SMSCs) in the process. This study aimed to investigate the potential factors that drive the development of bone morphological features in HOA by investigating the characteristics of the synovium, differentiation potential of SMSCs, and composition of synovial fluid in different types of HOA. METHODS: Synovial tissue and fluid were collected from 30 patients who underwent total hip arthroplasty (THA) with the variable bone morphology of HOA patients. RNA sequencing analysis and quantitative reverse transcription-polymerase chain reaction (RT-qPCR) were performed to analyse the genes in the normotrophic and hypertrophic synovial tissue. SMSCs were isolated and cultured from the normotrophic and hypertrophic synovial tissues of each hip joint in accordance with the variable bone morphology of HOA patients. Cell differentiation potential was compared using differentiation and colony-forming unit assays. Cytokine array was performed to analyse the protein expression in the synovial fluid. RESULTS: In the RNA sequencing analysis, 103 differentially expressed genes (DEGs) were identified, predominantly related to the interleukin 17 (IL-17) signalling pathway. Using a protein-protein interaction (PPI) network, 20 hub genes were identified, including MYC, CXCL8, ATF3, NR4A1, ZC3H12A, NR4A2, FOSB, and FOSL1. Among these hub genes, four belonged to the AP-1 family. There were no significant differences in the tri-lineage differentiation potential and colony-forming capacity of SMSCs. However, RT-qPCR revealed elevated SOX9 expression levels in synovial tissues from the hypertrophic group. The cytokine array demonstrated significantly higher levels of CXCL8, MMP9, and VEGF in the synovial fluid of the hypertrophic group than in the normotrophic group, with CXCL8 and MMP9 being significantly expressed in the hypertrophic synovium. CONCLUSION: Upregulation of AP-1 family genes in the synovium and increased concentrations of CXCL8, MMP9, and VEGF were detected in the synovial fluid of the hypertrophic group of HOA patients, potentially stimulating the differentiation of SMSCs towards the cartilage and thereby contributing to severe osteophyte formation.

Association of AI-determined Kellgren-Lawrence grade with medial meniscus extrusion and cartilage thickness by AI-based 3D MRI analysis in early knee osteoarthritis.

The associations among Kellgren-Lawrence (KL) grade, medial meniscus extrusion (MME), and cartilage thickness in knee osteoarthritis (OA) remain insufficiently understood. Our aim was to determine these associations in early to moderate medial tibiofemoral knee OA. We included 469 subjects with no lateral OA from the Kanagawa Knee Study. KL grade was assessed using artificial intelligence (AI) software. The MME was measured by MRI, and the cartilage thickness was evaluated in 18 subregions of the medial femorotibial joint by another AI system. The median MME width was 1.4 mm in KL0, 1.5 mm in KL1, 2.4 mm in KL2, and 6.0 mm in KL3. Cartilage thinning in the medial femur occurred in the anterior central subregion in KL1, expanded inwardly in KL2, and further expanded in KL3. Cartilage thinning in the medial tibia occurred in the anterior and middle external subregions in KL1, expanded into the anterior and middle central subregions in KL2, and further expanded in KL3. The absolute correlation coefficient between MME width and cartilage thickness increased as the KL grade increased in some subregions. This study provides novel insights into the early stages of knee OA and potentially has implications for the development of early intervention strategies.

Morphological analysis of three-dimensional MR images of patellofemoral joints in asymptomatic subjects.

The existing methods for analyzing patellofemoral (PF) osteoarthritis (OA) are limited. Our purpose was to clarify the frequency, localization, and morphological progression of PFOA by observing three-dimensional (3D) magnetic resonance (MR) images from a cohort population. The subjects were 561 patients aged 30-79 years from the Kanagawa Knee Study who had not visited a hospital for more than three consecutive months for knee symptoms. MR images of the PF joints, separated into the medial and lateral types, were presented in order of the highest to lowest patella cartilage area ratios. Cartilage defects in the patella were detected in 37 subjects (6.6%). Medial lesions (4.6%) were significantly more frequent than lateral lesions (2.0%) (p < 0.01). For both medial and lateral lesions, the patellar cartilage defects were divided into confined and unconfined types. The 3D MR images of the PF joint showed that the patellar cartilage defect occurred along each ridge of the femoral trochlea. The 3D MR images revealed a 6.6% prevalence of patellar cartilage defects, higher in the medial than lateral regions. The 3D MR images can easily determine PF morphology and cartilage defect location, making them useful in understanding the pathophysiology and etiology of PFOA.

Osteolytic Bone Loss and Skeletal Deformities in a Mouse Model for Early-Onset Paget's Disease of Bone with PFN1 Mutation Are Treatable by Alendronate.

A novel osteolytic disorder due to PFN1 mutation was discovered recently as early-onset Paget's disease of bone (PDB). Bone loss and pain in adult PDB patients have been treated using bisphosphonates. However, therapeutic strategies for this specific disorder have not been established. Here, we evaluated the efficiency of alendronate (ALN) on a mutant mouse line, recapitulating this disorder. Five-week-old conditional osteoclast-specific Pfn1-deficient mice (Pfn1-cKOOCL) and control littermates (33 females and 22 males) were injected with ALN (0.1 mg/kg) or vehicle twice weekly until 8 weeks of age. After euthanizing, bone histomorphometric parameters and skeletal deformities were analyzed using 3D µCT images and histological sections. Three weeks of ALN administration significantly improved bone mass at the distal femur, L3 vertebra, and nose in Pfn1-cKOOCL mice. Histologically increased osteoclasts with expanded distribution in the distal femur were normalized in these mice. Geometric bone shape analysis revealed a partial recovery from the distal femur deformity. A therapeutic dose of ALN from 5 to 8 weeks of age significantly improved systemic bone loss in Pfn1-cKOOCL mice and femoral bone deformity. Our study suggests that preventive treatment of bony deformity in early-onset PDB is feasible.

Mesenchymal stem cells in synovial fluid increase in number in response to synovitis and display more tissue-reparative phenotypes in osteoarthritis.

BACKGROUND: Synovial fluid mesenchymal stem cells (SF-MSCs) originate in the synovium and contribute to the endogenous repair of damaged intra-articular tissues. Here, we clarified the relationship between their numbers and joint structural changes during osteoarthritis (OA) progression and investigated whether SF-MSCs had phenotypes favorable for tissue repair, even in an OA environment. METHODS: Partial medial meniscectomy (pMx) and sham surgery were performed on both knees of rats. SF and knee joints were collected from intact rats and from rats at 2, 4, and 6 weeks after surgery. SF was cultured for 1 week to calculate the numbers of colony-forming cells and colony areas. Joint structural changes were evaluated histologically to investigate their correlation with the numbers and areas of colonies. RNA sequencing was performed for SF-MSCs from intact knees and knees 4 weeks after the pMx and sham surgery. RESULTS: Colony-forming cell numbers and colony areas were greater in the pMx group than in the intact and sham groups and peaked at 2 and 4 weeks, respectively. Synovitis scores showed the strongest correlation with colony numbers (R = 0.583) and areas (R = 0.456). RNA sequencing revealed higher expression of genes related to extracellular matrix binding, TGF-ß signaling, and superoxide dismutase activity in SF-MSCs in the pMx group than in the sham group. CONCLUSION: The number of SF-MSCs was most closely correlated with the severity of synovitis in this rat OA model. Tissue-reparative gene expression patterns were observed in SF-MSCs from OA knees, but not from knees without intra-articular tissue damage.

Older Age, Poor Preoperative Quadriceps Muscle Strength, and Residual Pain as Risk Factors for Poor Quadriceps Muscle Strength Recovery at 1 Year After ACL Reconstruction: A TMDU MAKS Study of 402 Patients.

Background: Poor postoperative quadriceps muscle strength recovery after anterior cruciate ligament reconstruction (ACLR) leads to delayed return to sports and lower patient satisfaction. Purpose/Hypothesis: The purpose of this study was to examine factors that affect quadriceps muscle strength 1 year after ACLR. It was hypothesized that older age, poor preoperative quadriceps muscle strength, and residual pain would be risk factors for poor quadriceps muscle strength recovery. Study Design: Case-control study; Level of evidence, 3. Methods: Included were patients from multiple institutions who underwent primary ACLR using autologous hamstring tendon grafts between August 1, 2013, and March 31, 2018, and who had at least 1 year of follow-up data. Patients with past ligamentous injuries in the affected knee, previous injuries or operations in the contralateral knee, accompanying ligament injuries of grade 2 or 3, or inflammatory or other types of osteoarthritis were excluded. Patients were categorized as having muscle strength ≥80% (good strength recovery) or <80% (poor strength recovery) compared with the contralateral leg at 1 year postoperatively. Multivariate logistic regression analysis was performed to investigate the factors influencing postoperative quadriceps muscle strength. In addition, a categorical analysis was conducted based on factors extracted by the multivariate logistic regression analysis. Results: A total of 402 patients were included. Multivariate logistic regression analysis revealed that age at surgery (P = .020), preoperative quadriceps muscle strength (P = .006), and postoperative Knee injury and Osteoarthritis Outcome Score (KOOS)-Pain score (P = .002) were significantly associated with quadriceps muscle strength at 1 year postoperatively. The odds of poor muscle strength recovery according to categorical analysis were 5.0-fold higher for patients aged >40 versus ≤20 years, 4.2-fold higher for those with preoperative quadriceps muscle index <60% versus ≥80%, and 7.7-fold higher for those with a postoperative KOOS-Pain score of <85 versus 100. Conclusion: Older age, poor preoperative quadriceps muscle strength, and low postoperative KOOS-Pain score were risk factors for poor quadriceps muscle strength 1 year after primary ACLR. Surgical indications, including age, preoperative active rehabilitation, and pain control, should be considered for optimization of postoperative quadriceps muscle strength recovery.

Volatile organic compounds and ionic substances contamination in cell processing facilities during rest period; a preliminary assessment of exposure to cell processing operators.

Introduction: Cell processing operators (CPOs) use a variety of disinfectants that vaporize in the workspace environment. These disinfectants can induce allergic reactions in CPOs, due to their long working hours at cell processing facilities (CPFs). Ionic substances such as CH3COO- generated from peracetic acid, nitrogen oxides (NOx) and sulfur oxides (SOx) from outdoor environment are also known to pollute air. Therefore, our objective was to assess the air quality in CPFs and detect volatile organic compounds (VOCs) from disinfectants and building materials, and airborne ionic substances from outdoor air. Methods: Sampling was conducted at three CPFs: two located in medical institutions and one located at a different institution. Air samples were collected using a flow pump. Ion chromatographic analysis of the anionic and cationic compounds was performed. For VOC analysis, a thermal desorption analyzer coupled with capillary gas chromatograph and flame ionization detector was used. Results: Analysis of the ionic substances showed that Cl-, NOx, and SOx, which were detected in large amounts in the outdoor air, were relatively less in the CPFs. Ethanol was detected as the main component in the VOC analysis. Toluene was detected at all sampling points. As compared to the other environments, air in the incubator contained larger amounts of VOCs, that included siloxane, tetradecane, and aromatics. Conclusions: No VOCs or ionic substances of immediate concern to the health of the CPOs were detected during the non-operating period. However, new clinical trials of cell products are currently underway in Japan, and a variety of new cell products are expected to be approved. With an increase in cell processing, health risks to CPOs that have not been considered previously, may become apparent. We should continue to prepare for the future expansion of the industry using a scientific approach to collect various pieces of information and make it publicly available to build a database.

Therapeutic effect of C-type natriuretic peptide on persistent pain in a rat knee arthritis model.

BACKGROUND: Intra-articular injection of C-type natriuretic peptide (CNP) at the acute inflammatory stage suppressed fibrotic changes in the infrapatellar fat pad (IFP), articular cartilage degeneration, and persistent pain in a monoiodoacetic acid (MIA)-induced rat knee arthritis model. In this study, we administered CNP during the inflammation subsiding period to evaluate CNP effectiveness in knees with osteoarthritis (OA) pathology. METHODS: 20 male Wistar rats were randomly divided into two groups. The rats received an intra-articular injection of MIA solution in the right knee to induce inflammation-induced joint degeneration. One group subsequently received an intra-articular CNP injection for six consecutive days from day 8, whereas another group received vehicle solution. Pain avoidance behavior tests and histological analyses were conducted to examine the therapeutic effects of CNP. RESULTS: The incapacitance test indicated that the percent weight on the ipsilateral limb decreased after MIA injection by day 4 and continued to decrease until the end of the experiment in the vehicle group, suggesting persistent pain in the knee. Intra-articular injection of CNP reversed the weight-bearing ratio on day 19. Histological evaluation showed that the CNP group had more residual fat tissue in the IFP and fewer calcitonin gene-related peptide-positive nerve endings compared to the vehicle group. CNP could not reverse articular cartilage degeneration. CONCLUSIONS: Intra-articular injection of CNP after the IFP fibrosis onset had no significant effect on OA severity and extent. Nevertheless, CNP might be utilized therapeutically for OA treatment since it can alleviate persistent knee pain and inhibit structural changes in residual fat tissue.

Decision regret following opening wedge high tibial osteotomy: Older age as a risk factor.

BACKGROUND: Understanding risk factors that can predict decision regret after surgical procedures can potentially increase the quality of patient decision making and reduce decision regret after opening wedge high tibial osteotomy (OWHTO). The purpose of the present study was to identify the risk factors that predict the likelihood of decision regret after OWHTO. METHOD: Questionnaires were administered to 98 eligible OWHTO recipients more than one year post-operatively. They answered "Yes" or "No" to the question "Would you go for the same choice (OWHTO) if you had to do it over again?" Univariate and multivariate logistic regression analyses were conducted using the decision regret questionnaire as the dependent variable against patient characteristics and surgery related factors. A receiver operating characteristic curve and area under the curve were constructed and calculated for age at surgery. Cut-off values were determined using the Youden principle and receiver operating characteristic curves. RESULTS: Among the 98 respondents, 18 (18%) reported regretting their decision. Older age at surgery was the only predictive risk factor for decision regret (P < 0.01). The area under the curve for the model using age to predict failure was 0.722. The cut-off value was 71 years. Patients aged 71 years or more had a 7.841 odds ratio for decision regret (P < 0.01). CONCLUSIONS: Older age emerged as a predictive risk factor for decision regret after OWHTO. Patients aged 71 years or older had a higher decision regret rate after OWHTO than younger patients and should more carefully weigh the suitability of OWHTO against other options.

Association of Infrapatellar Fat Pad Fibrosis at 3 Months After ACL Reconstruction With Short-term Clinical Outcomes and Inflammatory Cytokine Levels in the Synovial Fluid.

Background: Infrapatellar fat pad (IFP) fibrosis is reportedly associated with anterior knee pain and the progression of patellofemoral osteoarthritis after anterior cruciate ligament reconstruction (ACLR). However, causes of IFP fibrosis after ACLR have not been sufficiently investigated. Purpose: To compare the descriptive characteristics, clinical outcomes, and inflammatory cytokine levels in the synovial fluid between patients who underwent ACLR with versus without severe IFP fibrosis. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who underwent primary ACLR using autologous hamstring tendon were divided into 2 groups based on magnetic resonance imaging IFP fibrosis scoring (grades 0-5) at 3 months after surgery: the severe fibrosis group (grades 4 and 5) and mild fibrosis group (grades 0-3). Synovial fluid was aspirated on postoperative day 3 or 4 to measure inflammatory cytokine levels. Patient characteristics, clinical outcomes at 3 and 12 months after surgery, and inflammatory cytokine (interleukin [IL]-1ß, IL-2, IL-6, IL-8, IL-10, tumor necrosis factor-α, and interferon-γ) levels were compared between the groups. Results: Of the 36 patients included, 7 were allocated to the severe fibrosis group and 29 were allocated to the mild fibrosis group. The severe fibrosis group had a significantly longer operation time (153.0 vs 116.5 minutes for mild fibrosis; P = .007). Compared with the mild fibrosis group, the severe fibrosis group had greater pain during stair climbing (2.0 vs 0.7; P = .01) and a lower extension muscle strength ratio (operated/healthy side, 52.9% vs 76.1%; P < .001) at 3 months, and the severe fibrosis group had a lower Lysholm score (93.7 vs 97.3; P = .026) and greater knee extension (0.3° vs 1.9°; P = .043) and flexion angle restriction (142.9° vs 149.0°; P = .013) at 12 months. The severe fibrosis group demonstrated higher IL-1ß (2.6 vs 1.4 pg/mL; P = .022), IL-6 (2.0 vs 1.1 ng/mL; P = .029), and interferon-γ levels (11.3 vs 4.0 pg/mL; P = .044). Conclusion: Severe IFP fibrosis was associated with a longer operation time, higher inflammatory cytokine level in the synovial fluid, and worse clinical outcomes at 3 and 12 months after ACLR.

Comparison of the effects of oxidative and inflammatory stresses on rat chondrocyte senescence.

Osteoarthritis (OA) is an age-related degenerative joint disease that causes progressive cartilage loss. Chondrocyte senescence is a fundamental mechanism that contributes to the imbalance of matrix homeostasis in OA by inducing senescence-associated secretory phenotype (SASP). Although OA chondrocytes are mainly exposed to oxidative and inflammatory stresses, the role of these individual stresses in chondrocyte senescence remains unclear. In this study, we compared the effects of these stresses on the senescence of rat chondrocytes. Rat chondrocytes were treated with H2O2 and a combination of IL-1ß and TNF-α (IL/TNF) to compare their in vitro effect on senescent phenotypes. For in vivo evaluation, H2O2 and IL/TNF were injected into rat knee joints for 4 weeks. The in vitro results showed that H2O2 treatment increased reactive oxygen species, γ-H2AX, and p21 levels, stopped cell proliferation, and decreased glycosaminoglycan (GAG)-producing ability. In contrast, IL/TNF increased the expression of p16 and SASP factors, resulting in increased GAG degradation. Intraarticular injections of H2O2 did not cause any changes in senescent markers; however, IL/TNF injections reduced safranin O staining and increased the proportion of p16- and SASP factor-positive chondrocytes. Our results indicate that oxidative and inflammatory stresses have significantly different effects on the senescence of rat chondrocytes.

Augmentation of a Nonanatomical Repair of a Medial Meniscus Posterior Root Tear With Centralization Using Three Knotless Anchors May Be Associated With Less Meniscal Extrusion and Better Compressive Load Distribution in Mid-Flexion Compared With Non-Anatomical Root Repair Alone in a Porcine Knee Model.

PURPOSE: To investigate the biomechanics of the centralization augmentation using knotless soft anchors to a nonanatomical transtibial pull-out root repair in a porcine medial meniscus posterior root tear (MMPRT) model. METHODS: Porcine knee joints (N = 10) were used to perform one of the following procedures: (1) intact; (2) MMPRT; (3) nonanatomical root repair; (4) nonanatomical root repair with centralization using 2 anchors: anchors were inserted at the posterior medial collateral ligament (MCL) border and 10 mm anterior to the posterior MCL border; and (5) nonanatomical root repair with centralization using 3 anchors: another anchor was placed 10 mm posterior to the posterior MCL border. Contact area on the medial meniscus (MM), contact pressure in the MM and tibial cartilage, and MM extrusion were evaluated at 30°, 45°, 60°, and 90° knee flexions under 200 N compressive force. RESULTS: MM extrusion at the posterior MCL border was significantly reduced after root repair with centralization using 3 anchors than after root repair alone at 30° (-0.063 mm vs 1.5 mm, P = .017), 45° (0.21 mm vs 1.7 mm, P = .018), and 60° (0.78 mm vs 2.3 mm, P = .019). There were no significant differences in MM extrusion between the root repair alone and root repair with centralization using 2 anchors at all flexion angles. The contact area in the middle and posterior MM was significantly greater after centralization with 3 anchors than after root repair alone at all flexion angles (except the posterior MM at 90°). The mean contact pressure in the tibial cartilage was significantly lower after centralization with 3 anchors than after root repair at all angles. CONCLUSIONS: Augmentation of a nonanatomical repair of a medial meniscus posterior root tear with centralization using three knotless anchors may be associated with less meniscal extrusion and better compressive load distribution between 30° and 60° flexion compared with nonanatomical root repair alone in a porcine model. CLINICAL RELEVANCE: This biomechanical study at time zero suggests that the addition of centralization using 3 knotless anchors may reduce MM extrusion and restore the load-distributing function of the MM.