Factors to improve odds of success following medial opening-wedge high tibial osteotomy: a machine learning analysis.

BACKGROUND: Although high tibial osteotomy (HTO) is an established treatment option for medial compartment osteoarthritis, predictive factors for HTO treatment success remain unclear. This study aimed to identify informative variables associated with HTO treatment success and to develop and internally validate machine learning algorithms to predict which patients will achieve HTO treatment success for medial compartmental osteoarthritis. METHODS: This study retrospectively reviewed patients who underwent medial opening-wedge HTO (MOWHTO) at our center between March 2010 and December 2015. The primary outcomes were a lack of conversion to total knee arthroplasty (TKA) and achievement of a minimal clinically important difference of improvement in the Knee Injury and Osteoarthritis Outcome Score (KOOS) at a minimum of five years postoperatively. Recursive feature selection was used to identify the combination of variables from an initial pool of 25 features that optimized model performance. Five machine learning algorithms (XGBoost, multilayer perception, support vector machine, elastic-net penalized logistic regression, and random forest) were trained using five-fold cross-validation three times and applied to an independent test set of patients. The performance of the model was evaluated by the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 231 patients were included, and 200 patients (86.6%) achieved treatment success at the mean of 9 years of follow-up. A combination of seven variables optimized algorithm performance, and the following specific cutoffs increased the likelihood of MOWHTO treatment success: body mass index (BMI) ≤ 26.8 kg/m2, preoperative KOOS for pain ≤ 46.0, preoperative KOOS for quality of life ≤ 33.0, preoperative International Knee Documentation Committee score ≤ 42.0, preoperative Short-Form 36 questionnaire (SF-36) score > 42.25, three-month postoperative hip-knee-ankle angle > 1.0°, and three-month postoperative medial proximal tibial angle (MPTA) > 91.5° and ≤ 94.7°. The random forest model demonstrated the best performance (F1 score: 0.93; AUC: 0.81) and was transformed into an online application as an educational tool to demonstrate the capabilities of machine learning. CONCLUSIONS: The random forest machine learning algorithm best predicted MOWHTO treatment success. Patients with a lower BMI, poor clinical status, slight valgus overcorrection, and postoperative MPTA < 94.7 more frequently achieved a greater likelihood of treatment success. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Influences of Partial Anterior Cruciate Ligament Injury on Anterior Cruciate Ligament Tensional Force and Kinematic Stability During Walking.

Injuries in the anterior cruciate ligament (ACL), including partial tear and lengthening of the ACL, change the dynamic function of the knee. However, there is a lack of information on the effect of ACL partial tear on knee kinematics during walking. This study aimed to investigate the effects of different levels of ACL injuries on knee stability and ACL tensional force to identify the critical injury level. Motion data of five normal subjects were acquired along with the ground reaction force. A knee model with 14 ligaments was developed using cadaveric specimen data. The initial length and stiffness of the ACL were changed to develop ACL-injured knee models. Musculoskeletal simulations of the knee models were performed using the measured gait data. The average tibial anterior translation increased significantly by 2.6 ± 0.7 mm when the ACL stiffness decreased to 25% of its original stiffness. The average tibial anterior translation increased significantly by 2.6 ± 0.3 mm at an increase in initial length of 10%. The knee with partial ACL tear had a nonlinear decrease in ACL forces owing to the increase in the level of ACL injury, while the knee with ACL lengthening had linear decreased ACL forces. The partial tear of the ACL caused translational instability, while the complete tear caused both rotational and translational instabilities during the musculoskeletal walking simulation. This study presents the effects of partial ACL injuries on joint kinematics and ACL tensional force during the dynamic motion of walking.

Editorial Commentary: Alignment for Open-Wedge High Tibial Osteotomy Can Be Planned Using the Hip-Knee-Ankle Angle and the Weightbearing Line.

Correct alignment of the limb mechanical axis is a principal goal of open-wedge high tibial osteotomy and determines successful postoperative outcomes. Excessive postoperative joint line obliquity must be avoided. A mechanical medial proximal tibial angle (mMPTA) less than 95° results in poor outcomes. Preoperative planning is commonly performed using a picture archiving and communication system; however, this is time-consuming and sometimes inaccurate because many landmarks and parameters need to be confirmed manually. Hip-knee-ankle (HKA) angle and weightbearing line (WBL) percentage are perfectly correlated to the Miniaci angle when planning open-wedge high tibial osteotomy, and ΔmMPTA and ΔWBL percentage are nearly perfectly correlated with the ΔHKA angle. Surgeons can easily measure the Miniaci angle according to the preoperative HKA and preoperative WBL percentage without digital software, and mMPTA greater than 95° can be avoided. Finally, bony and soft tissue components must be considered during preoperative planning. Medial soft tissue laxity must be specifically avoided.

Combined Anterior Cruciate Ligament and Anterolateral Ligament Reconstruction Decreases Passive Anterior Tibial Subluxation Compared With Isolated Anterior Cruciate Ligament Reconstruction Despite Similar Rotational Stability and Clinical Outcomes.

PURPOSE: To analyze the effect of augmenting a hamstring autograft anterior cruciate ligament reconstruction (ACLR) with an anterolateral ligament reconstruction (ALLR) on a primary outcome of passive anterior tibial subluxation (PATS) and a secondary outcome of the clinical outcomes. METHODS: ACL-injured patients who underwent primary ACLR between March 2014 and February 2020 at our center were enrolled. Patients who underwent combined procedures (ACLR + ALLR) were matched in a 1:1 propensity ratio to patients who underwent ACLR only. We evaluated PATS, knee stability (side-to-side laxity difference, pivot-shift test), and patient-reported outcome measures (PROMs) after the procedure and documented complications. RESULTS: From an initial cohort of 252 patients with a minimum follow-up period of 2 years (48.4 ± 16.6 months), 35 matched pairs were included, and 17 patients (48.6%) in each group underwent second-look arthroscopy. The combined ACLR + ALLR group showed significantly better improvement of PATS in the lateral compartments than the isolated ACLR group (P = .034). There were no significant differences between the groups regarding knee stability (side-to-side laxity difference, pivot-shift test), PROMs, complications, and second-look arthroscopic findings (all P > .05). Moreover, the proportions of patients who achieved the minimal clinically important difference in PROMs were not different between groups. CONCLUSIONS: The combined ACLR + ALLR procedure was associated with a mean improvement in anterior tibial subluxation for the lateral compartment that was 1.2 mm better than an isolated ACLR procedure, despite its lack of clinical significance. LEVEL OF EVIDENCE: Level III, cohort study.

Increased medial meniscus extrusion led to worse clinical outcomes after medial opening-wedge high tibial osteotomy.

PURPOSE: Given that no studies have assessed the correlation between improvements in medial meniscus extrusion (MME) and clinical outcomes after medial opening-wedge high tibial osteotomy (MOWHTO), the present study aimed to measure the improvement in MME after MOWHTO and to investigate the correlation between the remaining postoperative MME and MOWHTO clinical outcomes by subgroup analysis. METHODS: This study included 79 patients (80 knees) who underwent MOWHTO with a minimum follow-up of 2 years. MME was measured pre- and postoperatively through magnetic resonance imaging after an average of 19.8 months following MOWHTO surgery. Clinical outcomes were evaluated according to the Knee Injury and Osteoarthritis Outcome Score (KOOS), the Tegner Activity Scale, and the Short-Form 36 questionnaire. In subgroup analysis, postoperative MME was classified into non-pathologic (≤ 3 mm) and pathologic (> 3 mm) groups. The clinical outcomes of the two groups were compared using Mann-Whitney U tests. A regression analysis was performed to determine the preoperative and postoperative characteristics associated with the improvement of MME. RESULTS: The mean (± standard deviation) values for pre- and postoperative MME were 3.6 (± 1.8) mm and 2.8 (± 1.5) mm, respectively (p < 0.001). In the subgroup analysis of postoperative MME, the non-pathologic group showed better improvement of KOOS than the pathologic group. Preoperative hip-knee-ankle angle was correlated with the improvement of medial meniscal extrusion in both univariate (p = 0.049) and multivariate (p = 0.015) analyses. CONCLUSION: The MME improved after MOWHTO, and the clinical outcomes were better for patients with a postoperative MME of less than 3 mm than for those with more than 3 mm. MME improvement after MOWHTO was correlated with preoperative varus alignment of the lower extremities. LEVEL OF EVIDENCE: III (Retrospective cohort study).

Higher survival rate in total knee arthroplasty after high tibial osteotomy than that after unicompartmental knee arthroplasty.

PURPOSE: The objective of this study was to evaluate the survival rates and complications in TKA after UKA and HTO as compared with primary TKA using national health data. It was hypothesized that survival and complication rates would be worse in patients with a history of UKA or HTO compared to primary TKA. METHODS: Based on a list of patients who underwent TKA from Korean National Health Insurance database, 315,071 underwent primary TKA (group A); 2177 TKA after HTO (group B); and 1284 TKA after UKA (group C). Revision rates were compared between the groups using log-rank tests and adjusted hazard ratios (HR) of groups B and C were compared with those of the reference group (group A). A total of 1000 TKA matched patients were assigned to groups B and C according to propensity score for comparing revision rates after TKA and perioperative complication rates between TKA after HTO and UKA. RESULTS: The overall revision rate was 2.1% in group A, 2.0% in group B, and 4.2% in group C. The revision rate until 10 years after TKA was significantly higher in group B (p = 0.03) or C (p < 0.0001) than in group A. The hazard ratios for revision was significantly higher in group A than in groups B and C at 10 years after index TKA (1.4 in group B and 3.7 in group C). The result of the comparison using PSM between TKA after HTO and UKA showed that TKA after HTO had lower risk of revision than TKA after UKA (HR: 0.41 at 10 years). However, no statistically significant differences in the perioperative complication rate between the two groups were found. (NS, not significant) CONCLUSIONS: TKA after UKA or HTO showed a significantly higher risk of revision than primary TKA. While TKA after HTO showed lower risk of revision than TKA after UKA, no significant differences in complications between TKA after UKA and HTO were found. Thus, surgeons must be aware of the low survival rate in TKA after UKA or HTO, especially in TKA after UKA. LEVEL OF EVIDENCE: III (Retrospective cohort study).

Preoperative Bone Marrow Edema Negatively Impacts 10-Year Outcomes After Unicompartmental Knee Arthroplasty.

BACKGROUND: The purpose of this study was to investigate the association between the extent of subchondral bone marrow edema (BME), as classified by magnetic resonance imaging, and intermediate to long-term outcomes after unicompartmental knee arthroplasty (UKA) for medial compartment osteoarthritis. METHODS: We enrolled 150 knees (144 patients) that underwent fixed-bearing UKA between April 2003 and December 2014 with a minimum follow-up of 5 years; the mean overall follow-up duration was 10 years (range, 5-18 years). We divided the patients into 2 groups based on the presence or absence of preoperative BME. Patients were also subdivided into 4 groups according to their BME scores determined by the magnetic resonance imaging Osteoarthritis Knee Score method. Clinical outcomes were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Forgotten Joint Score. Furthermore, survival rates and relevant risk factors that affect joint survivorship were analyzed. RESULTS: The groups with BME demonstrated significantly worse postoperative WOMAC pain and Forgotten Joint Scores at the final follow-up than the group without BME (all P < .05). We also found significant differences among the scores of groups with different BME grades (all P < .05). Post hoc analysis demonstrated differences between groups 1 and 2, 1 and 3, 1 and 4, and 2 and 4 (all P < .05) with a significant correlation between postoperative clinical outcomes and the extent of BME (r = 0.430 [WOMAC pain], r = -0.342 [Forgotten Joint Score]; P < .05). The survival rate was 95.4% for a mean period of 10 years for the UKAs, and the UKA survival was not associated with the presence of BME (P = .232; log-rank test). CONCLUSION: At a mean of 10 years, preoperative BME negatively impacted the clinical outcomes, especially pain, after UKA. However, UKA contributed to excellent survival rates for the same duration of follow-up, regardless of BME severity. Although this study does not provide any evidence that preoperative BME should be identified as a contraindication, evaluation of BME can provide crucial information about the expected outcomes.

Outcome Prediction Model Following Proximal Femoral Osteotomy in Legg-Calvé-Perthes Disease Using Machine Learning Algorithms.

BACKGROUND: The purpose of the current study was (1) to analyze various factors that may be associated with the outcomes of Legg-Calvé-Perthes disease (LCPD), and (2) to develop and internally validate machine learning algorithms capable of providing patient-specific predictions of which patients with LCPD will achieve relevant improvement in radiologic outcomes after proximal femoral varus osteotomy (PFVO). We examined several variables, previously identified as factors, that may influence the outcome of LCPD and developed a machine learning algorithm based on them. METHODS: In this retrospective study, we analyzed patients aged older than  6 years at the time of LCPD diagnosis who underwent PFVO at our institution between 1979 and 2015. Univariate and multivariate logistic regression analyses were used to examine the effects of variables on the sphericity of the femoral head at skeletal maturity, including age at onset, sex, stage at operation, extent of epiphyseal involvement and collapse, presence of specific epiphyseal, metaphyseal, and acetabular changes, and postoperative neck shaft angle (NSA). Recursive feature selection was used to identify the combination of variables from an initial pool of 13 features that optimized the model performance. Five machine learning algorithms [extreme gradient boosting (XGBoost), multilayer perception, support vector machine, elastic-net penalized logistic regression, and random forest) were trained using 5-fold cross-validation 3 times and applied to an independent testing set of patients. RESULTS: Ninety patients with LCPD who underwent PFVO were included in this study. The mean age at diagnosis was 7.93 (range, 6.0 to 12.33) years. The average follow-up period was 10.11 (range, 5.25 to 22.92) years. A combination of 8 variables, optimized algorithm performance, and specific cutoffs were found to decrease the likelihood of achieving the 1 or 2 Stulberg classification: age at onset ≤ 8.06, lateral classification ≤ B, 12.40 < preoperative migration percentage (MP) ≤ 22.85, Catterall classification ≤ 2, 117.4 < postoperative NSA ≤ 122.90, -10.8 < postoperative MP ≤ 6.5, 139.65 < preoperative NSA ≤ 144.67, and operation at stage 1. The XGBoost model demonstrated the best performance (F1 score: 0.78; area under the curve: 0.84). CONCLUSIONS: The XGBoost machine learning algorithm achieved the best performance in predicting the postoperative radiologic outcomes in patients with LCPD who underwent PFVO. In our population, age at onset ≤ 8.06, lateral classification ≤ B, 12.40 < preoperative MP ≤ 22.85, Catterall classification ≤ 2, 117.4 < postoperative NSA ≤ 122.90, -10.8 < postoperative MP ≤ 6.5, 139.65 < preoperative NSA ≤ 144.67, and operation at an early stage had the likelihood of achieving the spherical femoral head for the patients with LCPD that underwent PFVO. After external validation, the online application of this model may enhance shared decision-making. LEVEL OF EVIDENCE: Level III-retrospective cohort study.

The fate of fungal periprosthetic joint infection after total knee arthroplasty.

PURPOSE: To demonstrate the clinical outcomes of patients with fungal periprosthetic joint infections (PJIs) after two-stage exchange arthroplasty combined with antifungal therapy. METHODS: We retrospectively reviewed the outcomes of 41 patients with fungal PJIs after primary total knee arthroplasty (TKA) in a single centre from January 1999 to October 2017. During the first stage of resection arthroplasty, antifungal-impregnated cement spacers (AICSs) were implanted in all patients. After systemic antifungal treatment during the interval between the two surgeries, delayed reimplantation as part of a two-stage exchange protocol was performed when patients were clinically stable. We defined treatment success as a well-functioning arthroplasty without any signs of PJI after a minimum follow-up of two years without antimicrobial suppression. Successful treatment was confirmed by repeat negative cultures as well as a return of inflammatory markers to normal levels. RESULTS: The treatment success rate was 63.4% at the final follow-up. Thirty-six of 41 patients (87.8%) met the criteria for second-stage revision after confirmation of complete infection control. The mean prosthesis-free interval was 6.6 months (range, 2.0-30.0 months). During follow-up after two-stage exchange arthroplasty, ten patients (27.7% of 36 patients) unfortunately experienced recurrence or relapse of infection after an average of 31.3 months (range, 2.7-135.6 months). The rate of survivorship free from reinfection was 94.4% at six months, 84.8% at one year, and 73.6% at two years. Cox proportional hazard regression analysis demonstrated that the prosthesis-free interval (HR = 1.016, p = 0.037) and mean length of antifungal treatment (HR = 0.226, p = 0.046) were potential risk factors for failure. CONCLUSION: Fungal PJIs led to devastating clinical outcomes despite even two-stage revision arthroplasty with the use of AICSs and antifungal medications.

Polynucleotides Suppress Inflammation and Stimulate Matrix Synthesis in an In Vitro Cell-Based Osteoarthritis Model.

Osteoarthritis (OA) is characterized by degeneration of the joint cartilage, inflammation, and a change in the chondrocyte phenotype. Inflammation also promotes cell hypertrophy in human articular chondrocytes (HC-a) by activating the NF-κB pathway. Chondrocyte hypertrophy and inflammation promote extracellular matrix degradation (ECM). Chondrocytes depend on Smad signaling to control and regulate cell hypertrophy as well as to maintain the ECM. The involvement of these two pathways is crucial for preserving the homeostasis of articular cartilage. In recent years, Polynucleotides Highly Purified Technology (PN-HPT) has emerged as a promising area of research for the treatment of OA. PN-HPT involves the use of polynucleotide-based agents with controlled natural origins and high purification levels. In this study, we focused on evaluating the efficacy of a specific polynucleotide sodium agent, known as CONJURAN, which is derived from fish sperm. Polynucleotides (PN), which are physiologically present in the matrix and function as water-soluble nucleic acids with a gel-like property, have been used to treat patients with OA. However, the specific mechanisms underlying the effect remain unclear. Therefore, we investigated the effect of PN in an OA cell model in which HC-a cells were stimulated with interleukin-1ß (IL-1ß) with or without PN treatment. The CCK-8 assay was used to assess the cytotoxic effects of PN. Furthermore, the enzyme-linked immunosorbent assay was utilized to detect MMP13 levels, and the nitric oxide assay was utilized to determine the effect of PN on inflammation. The anti-inflammatory effects of PN and related mechanisms were investigated using quantitative PCR, Western blot analysis, and immunofluorescence to examine and analyze relative markers. PN inhibited IL-1ß induced destruction of genes and proteins by downregulating the expression of MMP3, MMP13, iNOS, and COX-2 while increasing the expression of aggrecan (ACAN) and collagen II (COL2A1). This study demonstrates, for the first time, that PN exerted anti-inflammatory effects by partially inhibiting the NF-κB pathway and increasing the Smad2/3 pathway. Based on our findings, PN can potentially serve as a treatment for OA.

Comparison of survival rates between total knee arthroplasty after a previous anterior cruciate ligament reconstruction and primary total knee arthroplasty via propensity score matching.

INTRODUCTION: Although the survival rate of total knee arthroplasty (TKA) in patients treated with anterior cruciate ligament reconstruction (ACLR) is not as favorable as that in patients treated with primary TKA without ligament reconstruction, the exact survival rates and complications associated with these procedures are still controversial. Therefore, the purpose of the current study was to compare the revision rates of TKA in patients with knee osteoarthritis (OA) with a previous ACLR and those of patients with primary TKA with no history of knee surgery by using propensity score matching analysis. MATERIALS AND METHODS: A list of patients who underwent TKA from January 1, 2008 to May 31, 2019 was obtained from the Korean National Health Insurance database. Among these, 460 patients underwent TKA in a knee with a previous ACLR and 569,766 patients who underwent primary TKA due to degenerative OA. We performed propensity scoring matching to compare the revision rates including septic revision due to prosthetic joint infection after TKA and perioperative complication rates within 90 days after revision TKA between the two groups. RESULTS: Matched patients were assigned to one of the two groups (group A: 2,201 patients who underwent TKA due to primary OA, group B: 448 patients who underwent TKA in a knee with a previous ACLR) based on the propensity score. The total number of revisions per 1000 person-years was significantly higher in group B than in group A (10.16 vs 4.66, respectively). Group B showed a higher risk of revision than group A at 10 years post-TKA (hazard ratio: 2.49, 95% confidence interval: 1.30-4.77). However, group B showed a similar risk of septic revision as group A (p = 0.44). Perioperative complications within 90 days after TKA showed no significant differences between the groups. CONCLUSIONS: Surgeons should be aware of the relatively higher revision rate of TKA in patients who had previously undergone an ACLR compared to that in patients who underwent primary TKA.

A comparative study of 21,194 UKAs and 49,270 HTOs for the risk of unanticipated events in mid-age patients from the national claims data in South Korea.

BACKGROUND: Both high tibial osteotomy (HTO) and unicompartmental knee arthroplasty (UKA) are well-established treatments for medial knee osteoarthritis (OA). However, over the past 20 years, results of comparisons of long-term survival rates and outcomes have remained controversial. Furthermore, in patients at the boundary age, from 50 to 70 years, considering age as a treatment indication, selecting a surgical method is difficult. Therefore, we aimed to investigate conversion rates to total knee arthroplasty (TKA) and perioperative adverse outcomes between the two surgical methods in mid-age patients. METHODS: We extracted data from the Korean National Health Insurance claims database. A total of 70,464 patients aged between 50 and 70 years, considered as mid-age patients were included in the final study population. We used a multivariable Cox proportional hazard regression model, adjusting for potential confounders such as age, sex, insurance type, region of residence, hospital type, comorbidities, and the Charlson comorbidity Index (CCI). RESULTS: Of the 70,464 patients, 21,194 were treated with UKA and 49,270 were treated with HTO. HTO showed a higher risk of revision than UKA at five, and 10 years and during the whole observation period. The incidence of deep vein thromboembolism, and surgical site infection was significantly higher in UKA than in HTO. CONCLUSIONS: It is important to choose an appropriate surgical method considering that UKA has better results in terms of long-term survival rates but may have a higher incidence of various complications.

Allogenic umbilical cord blood-derived mesenchymal stromal cell implantation was superior to bone marrow aspirate concentrate augmentation for cartilage regeneration despite similar clinical outcomes.

PURPOSE: The aim of this study was to compare clinical and second-look arthroscopic outcomes between bone marrow aspirate concentrate (BMAC) augmentation and human umbilical cord blood-derived mesenchymal stromal cell (hUCB-MSC) implantation in high tibial osteotomy (HTO) for medial compartmental knee osteoarthritis and identify the relationship between articular cartilage regeneration and HTO outcomes. METHODS: A total of 176 patients who underwent HTO combined with a BMAC or hUCB-MSC procedure for medial compartment osteoarthritis (Kellgren-Lawrence grade 3) between June 2014 and September 2018 with a minimum follow-up of 2 years were reviewed. After HTO, multiple holes were drilled at cartilage defect sites of the medial femoral condyle (MFC), and then prepared BMAC or hUCB-MSCs in combination with scaffolds were implanted in the MFC lesions. After propensity score matching based on sex, age, body mass index, and lesion size, 55 patients in each of the BMAC and hUCB-MSC groups were successfully matched. Second-look arthroscopic findings were assessed according to the International Cartilage Repair Society (ICRS) Cartilage Repair Assessment (CRA) grading system and Koshino staging system. Clinical outcomes were evaluated using the International Knee Documentation Committee (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS), Short-Form 36 (SF-36), and Tegner activity scores. RESULTS: At a mean follow-up of 33 months, clinical outcomes including IKDC, KOOS, SF-36, and Tegner activity scores were significantly improved in both groups (p < 0.001); however, there were no differences between the two groups. Second-look arthroscopy showed better healing of regenerated cartilage in the hUCB-MSC group (Grade I [4 cases, 9.1%]; Grade II [30 cases, 68.2%]; Grade III [11 cases, 22.7%]) than in the BMAC group (Grade I [1 case, 2.7%]; Grade II [20 cases, 54.1%]; Grade III [11 cases, 29.7%]; Grade IV [5 cases, 13.5%]) according to the ICRS CRA grading system (p = 0.040). There was no significant intergroup difference in terms of defect coverage based on the Koshino staging system (p = 0.057). Moreover, ICRS CRA grades at second-look arthroscopy were significantly correlated with clinical outcomes (r = - 0.337; p = 0.002). CONCLUSION: There were no significant differences in the clinical outcomes between the two groups. Both treatments provided similar, reliable outcomes in terms of pain relief, functional scores, and quality of life at a mean follow-up of 33 months. However, hUCB-MSC implantation was more effective than BMAC augmentation for articular cartilage regeneration.

Role of Mesenchymal Stem Cells and Their Paracrine Mediators in Macrophage Polarization: An Approach to Reduce Inflammation in Osteoarthritis.

Osteoarthritis (OA) is a low-grade inflammatory disorder of the joints that causes deterioration of the cartilage, bone remodeling, formation of osteophytes, meniscal damage, and synovial inflammation (synovitis). The synovium is the primary site of inflammation in OA and is frequently characterized by hyperplasia of the synovial lining and infiltration of inflammatory cells, primarily macrophages. Macrophages play a crucial role in the early inflammatory response through the production of several inflammatory cytokines, chemokines, growth factors, and proteinases. These pro-inflammatory mediators are activators of numerous signaling pathways that trigger other cytokines to further recruit more macrophages to the joint, ultimately leading to pain and disease progression. Very few therapeutic alternatives are available for treating inflammation in OA due to the condition's low self-healing capacity and the lack of clear diagnostic biomarkers. In this review, we opted to explore the immunomodulatory properties of mesenchymal stem cells (MSCs) and their paracrine mediators-dependent as a therapeutic intervention for OA, with a primary focus on the practicality of polarizing macrophages as suppression of M1 macrophages and enhancement of M2 macrophages can significantly reduce OA symptoms.

Does meniscectomy have any advantage over conservative treatment in middle-aged patients with degenerative medial meniscus posterior root tear?

BACKGROUND: The best treatment for degenerative medial meniscus posterior root tear (MMPRT) remains controversial. This study aimed to compare the clinical and radiological outcomes of arthroscopic meniscectomy and conservative treatment for degenerative MMPRT. METHODS: From January 2007 to December 2014, 146 patients (Meniscectomy group, 90; Conservative group, 56) were evaluated. Clinical outcomes were assessed using the Visual Analog Scale, International Knee Documentation Committee subjective scoring scale, Tegner activity scale, and Lysholm knee scoring scale at the final follow-up. Radiologic outcomes evaluated the progression of osteoarthritis (OA) according to the Kellgren-Lawrence (K-L) classification. We compared the hip-knee-ankle angle (HKAA), medial proximal tibial angle, tibial posterior slope angle, and width of medial joint space. After an average follow-up of 6.3 years, the survivorship was analyzed using the Kaplan-Meier method. RESULTS: All clinical outcomes were significantly improved in both groups after treatment, with no significant differences between the two groups at the final follow-up. The progression of OA according to the K-L classification, HKAA and width of medial joint space was significantly advanced in the meniscectomy group (p = 0.03, 0.04, 0.03, respectively). The 10-year survival rates in the meniscectomy and conservative groups were 87 and 88%, respectively. CONCLUSIONS: This study demonstrated that both conservative treatment and meniscectomy provided symptomatic relief. However, it was confirmed that OA progression was more severe in the meniscectomy. We conclude that arthroscopic meniscectomy had no advantage over conservative treatment in terms of clinical outcomes and OA progression in middle-aged patients with MMPRT. LEVEL OF EVIDENCE: Level III; retrospective comparative study.

Editorial Commentary: Chronological Age Is Not Associated With Adverse Postoperative Outcomes After High Tibial Osteotomy: Contradiction of Another Dogma From the Past.

Open wedge high tibial osteotomy (OWHTO) is an established treatment option for treating medial compartmental knee osteoarthritis with varus deformity. Among several factors associated with postoperative outcomes, patient age is immensely decisive in reconstructive knee joint surgeries, including OWHTO and total knee arthroplasty. Surprisingly, the direct effect of age on OWHTO outcomes is poorly defined in current clinical practice. Recent research comparing clinical and radiologic outcomes according to age was introduced, and the influential predictor determining OWHTO outcomes was cartilage status rather than age. In the future, when deciding its suitability, OWHTO should absolutely be considered as an attractive treatment even in elderly patients without highly advanced cartilage degeneration; advanced age should not be identified as a risk factor but rather a potential indication for OWHTO. However, a large-scale long-term follow-up study is necessary to elucidate these findings.

Allogenic Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Are More Effective Than Bone Marrow Aspiration Concentrate for Cartilage Regeneration After High Tibial Osteotomy in Medial Unicompartmental Osteoarthritis of Knee.

PURPOSE: The purpose of this study was to compare the outcome of cartilage regeneration between bone marrow aspirate concentrate (BMAC) augmentation and allogeneic human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSCs) transplantation in high tibial osteotomy (HTO) with microfracture (MFX) for medial unicompartmental osteoarthritis (OA) of the knee in the young and active patient. METHODS: Between January 2015 and December 2019, the patients who underwent HTO and arthroscopy with MFX combined with BMAC or allogeneic hUCB-MSCs procedure for medial unicompartmental OA with kissing lesion, which was shown full-thickness cartilage defect (≥ International Cartilage Repair Society [ICRS] grade 3B) in medial femoral cartilage and medial tibial cartilage, were include in this study. Retrospectively we compared clinical outcomes, including Hospital for Special Surgery score, Knee Society Score (KSS) pain and function, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score between BMAC and hUCB-MSCs group at minimum of 1-year follow-up. Also, second-look arthroscopy was performed simultaneously with removal of the plate after complete bone union. Cartilage regeneration was graded by the ICRS grading system at second-look arthroscopy. Radiological measurement including hip-knee-ankle (HKA) angle, posterior tibial slope angle, and correction angle were assessed. RESULTS: Of 150 cases that underwent HTO with MFX combined with BMAC or allogeneic hUCB-MSCs procedure for medial unicompartmental OA, 123 cases underwent plate removal and second-look arthroscopy after a minimum of 1 year after the HTO surgery. Seventy-four cases were kissing lesion in medial femoral cartilage and medial tibial cartilage during initial HTO surgery. Finally, the BMAC group composed of 42 cases and hUCB-MSCs group composed of 32 cases were retrospectively identified in patients who had kissing lesions and second-look arthroscopies with a minimum of 1 year of follow-up. At the final follow-up of mean 18.7 months (standard deviation = 4.6 months), clinical outcomes in both groups had improved. However, there were no significant differences between the IKDC, WOMAC, or KSS pain and function scores in the 2 groups (P > .05). At second-look arthroscopy, the ICRS grade was significantly better in the hUCB-MSC group than in the BMAC group in both medial femoral and medial tibial cartilage (P = .001 for both). The average ICRS grade of the BMAC group improved from 3.9 before surgery to 2.8 after surgery. The average ICRS grade of the hUBC-MSC group improved from 3.9 before surgery to 2.0 after surgery. Radiological findings comparing postoperative HKA angle, posterior tibial slope angle, and correction angle showed no significant differences between the groups (P > .05). Therefore it was found that the postoperative correction amount did not affect the postoperative cartilage regeneration results. CONCLUSIONS: We found that the hUCB-MSC procedure was more effective than the BMAC procedure for cartilage regeneration in medial unicompartmental knee OA even though the clinical outcomes improved regardless of which treatment was administered. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Increased joint obliquity after open-wedge high tibial osteotomy induces pain in the lateral compartment: a comparative analysis of the minimum 4-year follow-up outcomes using propensity score matching.

PURPOSE: To analyze the effects of increased medial proximal tibial angle (MPTA) on the clinical outcomes and cartilage deterioration in the lateral compartment after a mean follow-up period of 4 years following open-wedge high tibial osteotomy (OWHTO) using propensity score matching (PSM) analysis. METHODS: Among 376 knees treated with OWHTO for medial unicompartmental osteoarthritis with varus deformity, 36 knees with MPTA increase of > 95° and 108 knees with MPTA increase of < 95° at the final follow-up were included. The baseline prognostic factors [age, sex, preoperative hip-knee-ankle (HKA) angle, body mass index, and preoperative knee range of motion] were equalized between the 2 groups using PSM; consequently, 31 pairs of patients were compared. The radiographic and clinical outcomes, including lateral compartment pain, were assessed. For 18 patients in each group, second-look arthroscopy and cartilage status assessment were performed. RESULTS: The preoperative demographics were similar between the groups. At the final follow-up, the HKA angle and joint line obliquity were significantly higher in the increased MPTA group. No significant differences were observed in the clinical outcomes between the groups. On second-look arthroscopy, significant cartilage deterioration of the lateral compartment was not observed in either group. Pain in the lateral compartment was experienced significantly more frequently in the increased MPTA group (p < 0.01). CONCLUSION: Although excessively increased MPTA after HTO had no significant effects on the clinical outcomes and cartilage deterioration in the lateral compartment at the minimum 4-year follow-up, lateral compartment pain was experienced significantly more frequently in the increased MPTA group.

Machine-learning algorithm that can improve the diagnostic accuracy of septic arthritis of the knee.

PURPOSE: Prompt diagnosis and treatment of septic arthritis of the knee is crucial. Nevertheless, the quality of evidence for the diagnosis of septic arthritis is low. In this study, the authors developed a machine learning-based diagnostic algorithm for septic arthritis of the native knee using clinical data in an emergency department and validated its diagnostic accuracy. METHODS: Patients (n = 326) who underwent synovial fluid analysis at the emergency department for suspected septic arthritis of the knee were enrolled. Septic arthritis was diagnosed in 164 of the patients (50.3%) using modified Newman criteria. Clinical characteristics of septic and inflammatory arthritis were compared. Area under the receiver-operating characteristic (ROC) curve (AUC) statistics was applied to evaluate the efficacy of each variable for the diagnosis of septic arthritis. The dataset was divided into independent training and test sets (comprising 80% and 20%, respectively, of the data). Supervised machine-learning techniques (random forest and eXtreme Gradient Boosting: XGBoost) were applied to develop a diagnostic model using the training dataset. The test dataset was subsequently used to validate the developed model. The ROC curves of the machine-learning model and each variable were compared. RESULTS: Synovial white blood cell (WBC) count was significantly higher in septic arthritis than in inflammatory arthritis in the multivariate analysis (P = 0.001). In the ROC comparison analysis, synovial WBC count yielded a significantly higher AUC than all other single variables (P = 0.002). The diagnostic model using the XGBoost algorithm yielded a higher AUC (0.831, 95% confidence interval 0.751-0.923) than synovial WBC count (0.740, 95% confidence interval 0.684-0.791; P = 0.033). The developed algorithm was deployed as a free access web-based application ( www.septicknee.com ). CONCLUSION: The diagnosis of septic arthritis of the knee might be improved using a machine learning-based prediction model. LEVEL OF EVIDENCE: Diagnostic study Level III (Case-control study).

Bone marrow aspirate concentration provided better results in cartilage regeneration to microfracture in knee of osteoarthritic patients.

PURPOSE: To determine whether microfracture with bone marrow aspirate concentrate (BMAC) improves functional outcome and cartilage regeneration better than microfracture alone in patients undergoing high tibial osteotomy (HTO) for medial unicompartmental osteoarthritis (OA). METHODS: Among 436 patients treated with HTO for medial unicompartmental OA with varus deformity between 2010 and 2016, clinical outcomes were retrospectively compared between the microfracture alone group (group I, 43 cases) and microfracture with BMAC augmentation group (group II, 48 cases). Of these, 64 patients underwent a second-look arthroscopic assessment. Clinical outcomes were compared based on the Knee Society Score (KSS), International Knee Documentation Committee (IKDC) subjective score, and Western Ontario and McMaster Universities Arthritis Index (WOMAC). Cartilage regeneration was assessed according to Koshino's staging system and the International Cartilage Repair Society (ICRS) Cartilage Repair Assessment (CRA) grading system. RESULTS: At the last follow-up, there were no significant intergroup differences in terms of KSS for pain and function (p > 0.05). Moreover, WOMAC scores were similar between the two groups (p > 0.05). Regarding second-look arthroscopy findings, according to Koshino's staging system, there was no significant intergroup difference in terms of defect coverage (p = 0.187). However, group II showed a significantly better mean CRA score than group I (p = 0.035). CONCLUSION: There were no significant differences in clinical outcomes and cartilage regeneration between the groups. However, the CRA score was significantly higher with BMAC augmentation and microfracture than microfracture alone. Therefore, BMAC augmentation had a synergistic effect for a better cartilage regeneration, although studies with a longer follow-up might help to confirm whether microfracture with BMAC augmentation would ensure better clinical outcomes than microfracture alone for the treatment of knee OA.