Early microRNA and metabolite changes after anterior cruciate ligament reconstruction surgery.

OBJECTIVES: Anterior cruciate ligament (ACL) reconstruction after injury does not prevent post-traumatic osteoarthritis (PTOA). Circulating microRNA (miRNA) and metabolite changes emerging shortly after ACL injury and reconstruction remain insufficiently defined, potentially harbouring early cues contributing to PTOA evolution. Moreover, their differential expression between females and males also may influence PTOA's natural trajectory. This study aims to determine alterations in plasma miRNA and metabolite levels in the early stages following ACL reconstruction and between females and males. METHODS: A cohort of 43 ACL reconstruction patients was examined. Plasma was obtained at baseline, 2 weeks, and 6 weeks post-surgery (129 biospecimens in total). High-throughput miRNA sequencing and metabolomics were conducted. Differentially expressed miRNAs and metabolites were identified using negative binomial and linear regression models, respectively. Associations between miRNAs and metabolites were explored using time and sex as co-variants, (pre-surgery versus 2 and 6 weeks post-surgery). Using computational biology, miRNA-metabolite-gene interaction and pathway analyses were performed. RESULTS: Levels of 46 miRNAs were increased at 2 weeks post-surgery compared to pre-surgery (baseline) using miRNA sequencing. Levels of 13 metabolites were significantly increased while levels of 6 metabolites were significantly decreased at 2 weeks compared to baseline using metabolomics. Hsa-miR-145-5p levels were increased in female subjects at both 2 weeks (log2-fold-change 0.71, 95%CI 0.22,1.20) and 6 weeks (log2-fold-change 0.75, 95%CI 0.07,1.43) post-surgery compared to males. In addition, hsa-miR-497-5p showed increased levels in females at 2 weeks (log2-fold-change 0.77, 95%CI 0.06,1.48) and hsa-miR-143-5p at 6 weeks (log2-fold-change 0.83, 95%CI 0.07,1.59). Five metabolites were decreased at 2 weeks post-surgery in females compared to males: L-leucine (-1.44, 95%CI -1.75,-1.13), g-guanidinobutyrate (-1.27, 95%CI 1.54,-0.99), creatinine (-1.17, 95%CI -1.44,-0.90), 2-methylbutyrylcarnitine (-1.76, 95%CI -2.17,-1.35), and leu-pro (-1.13, 95%CI -1.44,-0.83). MiRNA-metabolite-gene interaction analysis revealed key signalling pathways based on post-surgical time-point and in females versus males. CONCLUSION: MiRNA and metabolite profiles were modified by time and by sex early after ACL reconstruction surgery, which could influence surgical response and ultimately risk of developing PTOA.

Surgical restabilization reduces the progression of post-traumatic osteoarthritis initiated by ACL rupture in mice.

OBJECTIVE: People who sustain joint injuries such as anterior cruciate ligament (ACL) rupture often develop post-traumatic osteoarthritis (PTOA). In human patients, ACL injuries are often treated with ACL reconstruction. However, it is still unclear how effective joint restabilization is for reducing the progression of PTOA. The goal of this study was to determine how surgical restabilization of a mouse knee joint following non-invasive ACL injury affects PTOA progression. DESIGN: In this study, 187 mice were subjected to non-invasive ACL injury or no injury. After injury, mice underwent restabilization surgery, sham surgery, or no surgery. Mice were then euthanized on day 14 or day 49 after injury/surgery. Functional analyses were performed at multiple time points to assess voluntary movement, gait, and pain. Knees were analyzed ex vivo with micro-computed tomography, RT-PCR, and whole-joint histology to assess articular cartilage degeneration, synovitis, and osteophyte formation. RESULTS: Both ACL injury and surgery resulted in loss of epiphyseal trabecular bone (-27-32%) and reduced voluntary movement at early time points. Joint restabilization successfully lowered OA score (-78% relative to injured at day 14, p < 0.0001), and synovitis scores (-37% relative to injured at day 14, p = 0.042), and diminished the formation of chondrophytes/osteophytes (-97% relative to injured at day 14, p < 0.001, -78% at day 49, p < 0.001). CONCLUSIONS: This study confirmed that surgical knee restabilization was effective at reducing articular cartilage degeneration and diminishing chondrophyte/osteophyte formation after ACL injury in mice, suggesting that these processes are largely driven by joint instability in this mouse model. However, restabilization was not able to mitigate the early inflammatory response and the loss of epiphyseal trabecular bone, indicating that these processes are independent of joint instability.

The association between changes in clinical pain severity and IL-6 reactivity among patients undergoing total knee Arthroplasty: The moderating role of change in insomnia.

Knee osteoarthritis (KOA) is linked to an enhanced release of interleukin-6 (IL-6). Increased levels of IL-6 are associated with greater pain and insomnia. While total knee arthroplasty (TKA) typically results in the reduction of pain, for a subgroup of patients, pain does not improve. Understanding patients' propensity to upregulate IL-6 may provide insight into variation in the clinical success of TKA for improving pain, and insomnia may play an important modulatory role. We investigated the association between pre- and post-surgical changes in clinical pain and IL-6 reactivity, and whether change in insomnia moderated this association. Patients (n = 39) with KOA came in-person before and 3-months after TKA. At both visits, patients completed validated measures of clinical pain and insomnia, as well as underwent quantitative sensory testing (QST). Blood samples were collected to analyze IL-expression both before and after QST procedures to assess changes in IL-6 in response to QST (IL-6 reactivity). Patients were categorized into two groups based on change in clinical pain from pre- to post-surgery: 1) pain decreased > 2 points (pain improved) and 2) pain did not decrease > 2 points (pain did not improve). Based on this definition, 49 % of patients had improved pain at 3-months. Among patients with improved pain, IL-6 reactivity significantly decreased from pre- to post-surgery, whereas there was no significant change in IL-6 reactivity among those whose pain did not improve. There was also a significant interaction between pain status and change in insomnia, such that among patients whose insomnia decreased over time, improved pain was significantly associated with a reduction in IL-6 reactivity. However, among patients whose insomnia increased over time, pain status and change in IL-6 reactivity were not significantly associated. Our findings suggest that the resolution of clinical pain after TKA may be associated with discernible alterations in pro-inflammatory responses that can be measured under controlled laboratory conditions, and this association may be moderated by perioperative changes in insomnia. Randomized controlled trials which carefully characterize the phenotypic features of patients are needed to understand how and for whom behavioral interventions may be beneficial in modulating inflammation, pain, and insomnia.

Temperature-Mediated Neural Interventions in Knee Osteoarthritis: a Review of Cryoneurolysis and Cooled Radiofrequency Ablation with Ultrasound Guidance.

PURPOSE OF REVIEW: Knee osteoarthritis is a debilitating chronic disease affecting nearly half of the world's population at some point in their lives. Treatment of pain and loss of function associated with this disease has been limited. In this review, we seek to explore how neural interventions with ultrasound guidance may be an emerging option for non-pharmacologic pain relief in patients with knee osteoarthritis. RECENT FINDINGS: Cryoneurolysis techniques have been demonstrated to provide pain relief out to 150 days post-treatment in knee osteoarthritis in select individuals. There have also been studies of cryoneurolysis pre-operatively to total knee replacement providing reduced pain, reduced opioid use post-operatively, and shorter hospital length of stay. Cooled radiofrequency ablation (CRFA) has been demonstrated to significantly reduce pain, improve functionality, and reduce pharmacologic needs in knee osteoarthritis out to 2 years. Both interventions appear to have increased accuracy with ultrasound, and CRFA appears to be associated with improved patient outcomes. The research demonstrates the efficacy of both cryoneurolysis and cooled radiofrequency ablation in the treatment of knee osteoarthritis. Ultrasound guidance in neurolysis provides an additional tool with real-time, high-accuracy nerve localization. These therapies should be considered for certain patients to assist in pain management in the non-operative and post-operative phase of knee osteoarthritis management. Further research is needed to further define the long-term effects and the long-term utility of the techniques in knee pain.

Increased Risk of New-Onset Rheumatoid Arthritis Among Osteoarthritis Patients Received Total Knee Arthroplasty: a global federated health network analysis.

Background: Complications of total knee arthroplasty (TKA) had been widely discussed. However, whether TKA influence risk of rheumatoid arthritis (RA) in osteoarthritis patients remained uncertain. We intend to evaluate the risk of RA in osteoarthritis patients underwent TKA. Methods: In this retrospective cohort study, data was retrieved from the US collaborative networks in TriNetX research network. Within the study period between 2005 and 2017, osteoarthritis patients underwent TKA were enrolled as case cohort whereas osteoarthritis patients never underwent TKA were enrolled as control cohort. Covariates were matched via propensity score matching. Risk of RA in TKA patients were valuated under various follow-up time and sensitivity models. Results: Under 1-year, 3-year and 5-year of follow-up, TKA patients were associated with significantly elevated risk of RA, especially under 1-year follow-up (HR=1.74; 95% CI, 1.39-2.18). Subgroup analysis demonstrated a significant increase in the risk of RA following TKA in the female subgroup (HR=1.42; 95% CI, 1.24-1.63), the subgroup aged 18-64 years (HR=1.48; 95% CI, 1.11-1.97), and the subgroup aged greater than 65 years old (HR=1.38; 95% CI, 1.21-1.58) based on 5-year follow-up. Conclusion: Clinicians should be concerned about uncharted association between TKA and RA reported our current study. Additional prospective studies and in-depth mechanistic inquiries were warranted to determine the causation.

A Retrospective Study to Compare Patient Outcomes from Standard Total Knee Arthroplasty (TKA) versus Navigation-Guided Arthroplasty Using the Brainlab Software-Guided Surgical System at a Center in Hebei Province January 2021 to July 2023.

BACKGROUND This retrospective study aimed to compare patient outcomes from standard total knee arthroplasty (TKA) vs navigation-guided arthroplasty using the Brainlab software-guided surgical system at Cangzhou Hospital of Integrated TCM-WM, Hebei, Hebei Province, China from January 2021 to July 2023. MATERIAL AND METHODS A total of 239 patients who underwent total knee arthroplasty in Cangzhou Hospital of Integrated TCM-WM, Hebei from January 2021 to July 2023 were retrospectively analyzed. According to the inclusion criteria, 212 eligible patients were selected for analysis and divided into a Navigation Group (NG) (n=105) and a Traditional Group (TG) (n=107) according to surgical method used. Outcomes measured included duration of disease, operative time, intraoperative blood loss volume, postoperative length of hospital stay, and pain measured by the hospital for special surgery knee score (HSS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and forgotten joint score (FJS). RESULTS The comparison of perioperative results between the 2 groups showed that the incision length in the NG was significantly longer than that in the TG (P<0.001, 95% Cl 2.59-3.35). At 3 months after surgery, the HSS score of the NG was statistically higher than that of the TG (P=0.002, 95% Cl 3.42-4.46); the WOMAC score of the NG was lower than that of the TG (P<0.001, 95% Cl -4.41-2.87); and the FJS score of the NG was significantly higher than that of the TG (P=0.003, 95% Cl 2.39-3.67). CONCLUSIONS Compared with conventional TKA, use of the Brainlab navigation system is associated with a longer incision, more accurate implantation position of the prosthesis, faster recovery of knee joint function, and helps patients to "forget" about their knee prosthesis in the short term.

Incidence of knee and hip joint replacement associated with cumulative exposure to physical factors at work.

BACKGROUND: Knee osteoarthritis (OA) has been quite consistently associated with high physical workload and specific physical factors at work, while for hip OA, fewer studies are available, which still indicate possible associations with heavy lifting and physical workload. The objective of the study was to assess the association between exposure to workplace physical factors and incidence of knee and hip arthroplasty, as markers of severe OA in these joints. METHODS: The study population was composed of employees 25-60 years who participated in the Turin 2011 census. For each job held since 1995, exposure to physical factors was assigned to individuals in the cohort through a Job-Exposure Matrix constructed from the Italian O*NET database. Using Poisson regression models, the incidence of knee and hip arthroplasty for OA, identified through hospitalizations from 2012 to 2018, was examined in relation to cumulative exposure to 7 different physical hazards and a composite indicator of physical workload constructed from 17 physical factors (Ergo-Index). RESULTS: The risk of knee OA was significantly increased in the highest cumulative exposure quartile of physical workload (incidence rate ratio = 1.98, 95% confidence interval: 1.24-3.16) and of all single hazards examined, compared to the lowest quartile, with significant trends in risk with increasing exposure. In contrast, no association was found with hip OA, whose relative risks were close to or below one in all higher-exposure quartiles of physical workload and of each single hazard. CONCLUSIONS: Our results indicate that exposure to physical hazards at work increases the likelihood of developing knee OA, but not hip OA.

What Are the Underlying Mental Health Constructs Associated With Level of Capability in People With Knee and Hip Osteoarthritis?

BACKGROUND: Mental health characteristics such as negative mood, fear avoidance, unhelpful thoughts regarding pain, and low self-efficacy are associated with symptom intensity and capability among patients with hip and knee osteoarthritis (OA). Knowledge gaps remain regarding the conceptual and statistical overlap of these constructs and which of these are most strongly associated with capability in people with OA. Further study of these underlying factors can inform us which mental health assessments to prioritize and how to incorporate them into whole-person, psychologically informed care. QUESTIONS/PURPOSES: (1) What are the distinct underlying factors that can be identified using statistical grouping of responses to a multidimensional mental health survey administered to patients with OA? (2) What are the associations between these distinct underlying factors and capability in knee OA (measured using the Knee Injury and Osteoarthritis Outcome Score, Joint Replacement [KOOS JR]) and hip OA (measured using Hip Disability and Osteoarthritis Outcome Score, Joint Replacement [HOOS JR]), accounting for sociodemographic and clinical factors? METHODS: We performed a retrospective cross-sectional analysis of adult patients who were referred to our program with a primary complaint of hip or knee pain secondary to OA between October 2017 and December 2020. Of the 2006 patients in the database, 38% (760) were excluded because they did not have a diagnosis of primary osteoarthritis, and 23% (292 of 1246) were excluded owing to missing data, leaving 954 patients available for analysis. Seventy-three percent (697) were women, with a mean age of 61 ± 10 years; 65% (623) of patients were White, and 52% (498) were insured under a commercial plan or via their employer. We analyzed demographic data, patient-reported outcome measures, and a multidimensional mental health survey (the 10-item Optimal Screening for Prediction of Referral and Outcome-Yellow Flag [OSPRO-YF] assessment tool), which are routinely collected for all patients at their baseline new-patient visit. To answer our first question about identifying underlying mental health factors, we performed an exploratory factor analysis of the OSPRO-YF score estimates. This technique helped identify statistically distinct underlying factors for the entire cohort based on extracting the maximum common variance among the variables of the OSPRO-YF. The exploratory factor analysis established how strongly different mental health characteristics were intercorrelated. A scree plot technique was then applied to reduce these factor groupings (based on Eigenvalues above 1.0) into a set of distinct factors. Predicted factor scores of these latent variables were generated and were subsequently used as explanatory variables in the multivariable analysis that identified variables associated with HOOS JR and KOOS JR scores. RESULTS: Two underlying mental health factors were identified using exploratory factor analysis and the scree plot; we labeled them "pain coping" and "mood." For patients with knee OA, after accounting for confounders, worse mood and worse pain coping were associated with greater levels of incapability (KOOS JR) in separate models but when analyzed in a combined model, pain coping (regression coefficient -4.3 [95% confidence interval -5.4 to -3.2], partial R 2 0.076; p < 0.001) had the strongest relationship, and mood was no longer associated. Similarly, for hip OA, pain coping (regression coefficient -5.4 [95% CI -7.8 to -3.1], partial R 2 0.10; p < 0.001) had the strongest relationship, and mood was no longer associated. CONCLUSION: This study simplifies the multitude of mental health assessments into two underlying factors: cognition (pain coping) and feelings (mood). When considered together, the association between capability and pain coping was dominant, signaling the importance of a mental health assessment in orthopaedic care to go beyond focusing on unhelpful feelings and mood (assessment of depression and anxiety) alone to include measures of pain coping, such as the Pain Catastrophizing Scale or Tampa Scale for Kinesiophobia, both of which have been used extensively in patients with musculoskeletal conditions. LEVEL OF EVIDENCE: Level III, prognostic study.

High Area Deprivation Index is Associated With Not Achieving the Patient-acceptable Symptom State After TKA.

BACKGROUND: The Area Deprivation Index (ADI) approximates a patient's relative socioeconomic deprivation. The ADI has been associated with increased healthcare use after TKA, but it is unknown whether there is an association with patient-reported outcome measures (PROMs). Given that a high proportion of patients are dissatisfied with their results after TKA, and the large number of these procedures performed, knowledge of factors associated with PROMs may indicate opportunities to provide support to patients who might benefit from it. QUESTIONS/PURPOSES: (1) Is the ADI associated with achieving the minimum clinically important difference (MCID) for the Knee Injury and Osteoarthritis Outcome Score (KOOS) for pain, Joint Replacement (JR), and Physical Function (PS) short forms after TKA? (2) Is the ADI associated with achieving the patient-acceptable symptom state (PASS) thresholds for the KOOS pain, JR, and PS short forms? METHODS: This was a retrospective study of data drawn from a longitudinally maintained database. Between January 2016 and July 2021, a total of 12,239 patients underwent unilateral TKA at a tertiary healthcare center. Of these, 92% (11,213) had available baseline PROM data and were potentially eligible. An additional 21% (2400) of patients were lost before the minimum study follow-up of 1 year or had incomplete data, leaving 79% (8813) for analysis here. The MCID is the smallest change in an outcome score that a patient is likely to perceive as a clinically important improvement, and the PASS refers to the threshold beyond which patients consider their symptoms acceptable and consistent with adequate functioning and well-being. MCIDs were calculated using a distribution-based method. Multivariable logistic regression models were created to investigate the association of ADI with 1-year PROMs while controlling for patient demographic variables. ADI was stratified into quintiles based on their distribution in our sample. Achievement of MCID and PASS thresholds was determined by the improvement between preoperative and 1-year PROMs. RESULTS: After controlling for patient demographic factors, ADI was not associated with an inability to achieve the MCID for the KOOS pain, KOOS PS, or KOOS JR. A higher ADI was independently associated with an increased risk of inability to achieve the PASS for KOOS pain (for example, the odds ratio of those in the ADI category of 83 to 100 compared with those in the 1 to 32 category was 1.34 [95% confidence interval 1.13 to 1.58]) and KOOS JR (for example, the OR of those in the ADI category of 83 to 100 compared with those in the 1 the 32 category was 1.29 [95% CI 1.10 to 1.53]), but not KOOS PS (for example, the OR of those in the ADI category of 83 to 100 compared with those in the 1 the 32 category was 1.09 [95% CI 0.92 to 1.29]). CONCLUSION: Our findings suggest that social and economic factors are associated with patients' perceptions of their overall pain and function after TKA, but such factors are not associated with patients' perceptions of their improvement in symptoms. Patients from areas with higher deprivation may be an at-risk population and could benefit from targeted interventions to improve their perception of their healthcare experience, such as through referrals to nonemergent medical transportation and supporting applications to local care coordination services before proceeding with TKA. Future research should investigate the mechanisms underlying why socioeconomic disadvantage is associated with inability to achieve the PASS, but not the MCID, after TKA. LEVEL OF EVIDENCE: Level III, therapeutic study.

Human Infrapatellar Fat Pad Mesenchymal Stem Cell-derived Extracellular Vesicles Purified by Anion Exchange Chromatography Suppress Osteoarthritis Progression in a Mouse Model.

BACKGROUND: Extracellular vesicles derived from mesenchymal stem cells (MSCs) show great promise in treating osteoarthritis (OA). However, studies from the perspective of clinical feasibility that consider an accessible cell source and a scalable preparation method for MSC-extracellular vesicles are lacking. QUESTIONS/PURPOSES: (1) Does an infrapatellar fat pad obtained from patients undergoing TKA provide a suitable source to provide MSC-extracellular vesicles purified by anion exchange chromatography? Using an in vivo mouse model for OA in the knee, (2) how does injection of the infrapatellar fat pad-derived MSC-extracellular vesicles alter gait, cartilage structure and composition, protein expression (Type II collagen, MMP13, and ADAMTS5), subchondral bone remodeling and osteophytes, and synovial inflammation? METHODS: The infrapatellar fat pad was collected from three patients (all female; 62, 74, 77 years) during TKA for infrapatellar fat pad-derived MSC culturing. Patients with infection, rheumatic arthritis, and age > 80 years were excluded. MSC-extracellular vesicles were purified by anion exchange chromatography. For the animal study, we used 30 male C57BL/6 mice aged 10 weeks, divided into six groups. MSC-extracellular vesicles were injected weekly into the joint of an OA mouse model during ACL transection (ACLT). To answer our first research question, we characterized MSCs based on their proliferative potential, differentiation capacity, and surface antigen expression, and we characterized MSC-extracellular vesicles by size, morphology, protein marker expression, and miRNA profile. To answer our second research question, we evaluated the effects of MSC-extracellular vesicles in the OA mouse model with quantitative gait analysis (mean pressure, footprint area, stride length, and propulsion time), histology (Osteoarthritis Research Society International Score based on histologic analysis [0 = normal to 24 = very severe degeneration]), immunohistochemistry staining of joint sections (protein expression of Type II collagen, MMP13, and ADAMTS5), and micro-CT of subchondral bone (BV/TV and Tb.Pf) and osteophyte formation. We also examined the mechanism of action of MSC-extracellular vesicles by immunofluorescent staining of the synovium membrane (number of M1 and M2 macrophage cells) and by analyzing their influence on the expression of inflammatory factors (relative mRNA level and protein expression of IL-1ß, IL-6, and TNF-α) in lipopolysaccharide-induced macrophages. RESULTS: Infrapatellar fat pads obtained from patients undergoing TKA provide a suitable cell source for producing MSC-extracellular vesicles, and anion exchange chromatography is applicable for isolating MSC-extracellular vesicles. Cultured MSCs were spindle-shaped, proliferative at Passage 4 (doubling time of 42.75 ± 1.35 hours), had trilineage differentiation capacity, positively expressed stem cell surface markers (CD44, CD73, CD90, and CD105), and negatively expressed hematopoietic markers (CD34 and CD45). MSC-extracellular vesicles purified by anion exchange chromatography had diameters between 30 and 200 nm and a typical cup shape, positively expressed exosomal marker proteins (CD63, CD81, CD9, Alix, and TSG101), and carried plentiful miRNA. Compared with the ACLT group, the ACLT + extracellular vesicle group showed alleviation of pain 8 weeks after the injection, indicated by increased area (0.67 ± 0.15 cm 2 versus 0.20 ± 0.03 cm 2 , -0.05 [95% confidence interval -0.09 to -0.01]; p = 0.01) and stride length (5.08 ± 0.53 cm versus 6.20 ± 0.33 cm, -1.12 [95% CI -1.86 to -0.37]; p = 0.005) and decreased propulsion time (0.22 ± 0.06 s versus 0.11 ± 0.04 s, 0.11 [95% CI 0.03 to 0.19]; p = 0.007) in the affected hindlimb. Compared with the ACLT group, the ACLT + extracellular vesicles group had lower Osteoarthritis Research Society International scores after 4 weeks (8.80 ± 2.28 versus 4.80 ± 2.28, 4.00 [95% CI 0.68 to 7.32]; p = 0.02) and 8 weeks (16.00 ± 3.16 versus 9.60 ± 2.51, 6.40 [95% CI 2.14 to 10.66]; p = 0.005). In the ACLT + extracellular vesicles group, there was more-severe OA at 8 weeks than at 4 weeks (9.60 ± 2.51 versus 4.80 ± 2.28, 4.80 [95% CI 0.82 to 8.78]; p = 0.02), indicating MSC-extracellular vesicles could only delay but not fully suppress OA progression. Compared with the ACLT group, the injection of MSC-extracellular vesicles increased Type II collagen expression, decreased MMP13 expression, and decreased ADAMTS5 expression at 4 and 8 weeks. Compared with the ACLT group, MSC-extracellular vesicle injection alleviated osteophyte formation at 8 weeks and inhibited bone loss at 4 weeks. MSC-extracellular vesicle injection suppressed inflammation; the ACLT + extracellular vesicles group had fewer M1 type macrophages than the ACLT group. Compared with lipopolysaccharide-treated cells, MSC-extracellular vesicles reduced mRNA expression and inhibited IL-1ß, IL-6, and TNF-α in cells. CONCLUSION: Using an OA mouse model, we found that infrapatellar fat pad-derived MSC-extracellular vesicles could delay OA progression via alleviating pain and suppressing cartilage degeneration, osteophyte formation, and synovial inflammation. The autologous origin of extracellular vesicles and scalable purification method make our strategy potentially viable for clinical translation. CLINICAL RELEVANCE: Infrapatellar fat pad-derived MSC-extracellular vesicles isolated by anion exchange chromatography can suppress OA progression in a mouse model. Further studies with large-animal models, larger animal groups, and subsequent clinical trials are necessary to confirm the feasibility of this technique for clinical OA treatment.

Are There Racial and Ethnic Variations in Patient Attitudes Toward Hip and Knee Arthroplasty for Osteoarthritis? A Systematic Review.

BACKGROUND: It is not clear why people who identify as Black or Hispanic are less likely to undergo discretionary musculoskeletal surgery such as arthroplasty for osteoarthritis of the hip or knee. Inequities and mistrust are important factors to consider. The role of socioeconomic factors and variation in values, attitudes, and beliefs regarding discretionary procedures are less well understood. A systematic review of the evidence regarding mindsets toward knee and hip arthroplasty among Black and Hispanic people could inform attempts to limit disparities in care. QUESTIONS/PURPOSES: In a systematic review of qualitative and quantitative evidence, we asked: (1) What factors are associated with racial and ethnic variations in attitudes toward discretionary hip and knee arthroplasty for osteoarthritis? (2) Do studies that investigate racial and ethnic variations in mindsets toward discretionary orthopaedic care control for potential confounding by socioeconomic factors? METHODS: A systematic search of PubMed, Cochrane, and Embase (last searched August 2023) for studies that addressed racial and ethnic variations in mindsets toward discretionary musculoskeletal care use was conducted. We excluded studies that were not published in English, lacked full-text availability, and those that documented patient approaches without comparing them to the willingness to undergo a discretionary procedure. Twenty-one studies were included-14 quantitative and seven qualitative-including 8472 patients. The Mixed Methods Appraisal Tool was used for quality assessment of included studies. The studies included demonstrated low risk of bias: five quantitative studies lacked detail regarding nonresponse bias and one qualitative study lacked details regarding the racial and ethnic composition of its cohort. To answer our first research question, we categorized themes associated with racial differences in mindsets toward discretionary care and recorded the presence of associations in quantitative studies. To answer our second question, we identified whether quantitative studies address potential confounding with socioeconomic factors. There were no randomized trials, so no meta-analysis was performed. RESULTS: In general, self-identified Black and Hispanic patients had a lower preference for hip and knee arthroplasty than self-identified White patients. Black patients were more likely to regard osteoarthritis as a natural and irremediable part of aging and prefer home remedies. Both Black and Hispanic patients valued support from religion and were relatively cost-conscious. Black and Hispanic patients had lower perception of benefit, were less familiar with the procedure, had higher levels of fear regarding surgery and recovery, and had more-limited trust in care. Generally, Black and Hispanic social networks tended to address these concerns, whereas White social networks were more likely to discuss the benefits of surgery. Thirteen of 14 quantitative studies considered and accounted for potential confounding socioeconomic variables in their analyses. CONCLUSION: The observation that lower preference for discretionary arthroplasty among Black and Hispanic patients is independent from socioeconomic factors and is related to accommodation of aging, preference for agency (home remedies), greater consideration of costs, recovery concerns, and potential harms directs orthopaedic surgeons to find ways to balance equitable access to specialty care and discretionary surgery while avoiding undermining effective accommodation strategies. It is important not to assume that lower use of discretionary surgery represents poorer care or is a surrogate marker for discrimination. LEVEL OF EVIDENCE: Level III, therapeutic study.

Exploring the information needs of patients with osteoarthritis of the knee: a content analysis of Facebook group posts.

BACKGROUND: End-stage osteoarthritis of the knee (OAK) is often treated by total knee arthroplasty (TKA). This intervention can significantly improve quality of life. However, many patients are dissatisfied with the outcome of surgery. One of the factors related to dissatisfaction is the of lack integration of patients' preferences, habits and values that are not addressed by physicians. To develop realistic expectations, affected patients need evidence-based information. Our aim was to explore the information needs of patients with OAK to support the development of decision aids and consent forms to promote informed decision-making. Additionally, we investigated whether the information needs during the Covid-19 pandemic differ from those before the pandemic. METHODS: The qualitative research design included a social media analysis of Facebook groups. Facebook groups were selected according to the following criteria: Thematic relevance, English or German language, at least one new post per week, from period before and after the start of the Covid-19 pandemic in March 2020. Thematically relevant group posts were analysed according to the content-structuring content analysis of Kuckartz using MaxQDA. RESULTS: Out of 448 identified Facebook groups, we screened seven for relevant posts and a total of 77 posts out of 6 groups were selected. The following eight categories were derived during the coding process: access to health care, disease information, TKA indication and contraindication, TKA outcome and quality of life, information needs regarding conservative therapy, strain, attitude towards TKA and attitude towards conservative therapy. The analysis showed that patients with OAK need information about the benefits and risks of TKA and conservative therapies. CONCLUSION: This study provides information on the information needs of patients with OAK in order to decide between TKA or conservative therapy. Patients need information about treatment options in due consideration of their immediate living situation to be reliably able to assess potential outcomes. Such Information about TKA should enable patients to assess the individual prognosis with comprehensible and relevant outcome measures. Also, they should be formulated with the living environment of the patients in mind and be linked to possible fears and negative previous experiences with treatments.

Deficient gait function despite effect index of the Western Ontario and McMaster university osteoarthritis index score considered cured one year after bilateral total knee arthroplasty.

BACKGROUND: To clarify the value of gait analysis and its consistency with traditional scoring scales for the evaluation of knee joint function after total knee arthroplasty (TKA). METHODS: This study included 25 patients with knee osteoarthritis (KOA) who underwent bilateral TKA, and 25 conditionally matched healthy individuals, categorised into the experimental and control groups, respectively. Patients in the experimental group underwent gait analysis and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) evaluation before and 1 year after TKA. Weight-bearing balance and walking stability were assessed using discrete trends of relevant gait indicators. Pearson's correlation analysis was performed on the gait and WOMAC score data of the experimental group before and after TKA. RESULTS: One year after TKA, patients' gait indices (except gait cycle) were significantly better than before surgery, but significantly worse than that of the control group (P < 0.01). The shape of patients' plantar pressure curves did not return to normal. Additionally, the discrete trend of related gait indicators reflecting weight-bearing balance and walking stability were smaller than before TKA, but still greater than that of the control group. The WOMAC scores of patients 1 year after TKA were significantly lower than those before TKA (P < 0.001), and the efficacy index was > 80%. The WOMAC scores and gait analysis results were significantly correlated before TKA (P < 0.05). CONCLUSIONS: Gait analysis should be used in conjunction with scoring scales to assess joint functions.

Contralateral knee osteoarthritis is a risk factor for ipsilateral knee osteoarthritis progressing: a case control study.

BACKGROUND: Knee osteoarthritis (KOA) is a highly disabling disease, and studying its progression is crucial. However, it is still unclear whether the progression of ipsilateral knee osteoarthritis is influenced by contralateral knee osteoarthritis. METHODS: Data were collected from the OAI database and divided into two study cohorts (right/left KOA cohort). Each cohort had a target knee (right/left knee) and was further divided into two groups (exposure/control group). The demographic data of both cohorts were balanced at baseline by propensity score matching (PSM), and the data included rating scale and radiographic and clinical data. After checking for balance in the matched variables, we then compared the differences between the two groups in each cohort. Our primary focus was on the minimum joint space width (mJSW) of the target knee, which was measured four years after baseline. The secondary outcome was the arthroplasty rate of the target knee within nine years. RESULTS: In this study, a total of 678 participants were enrolled and matched. After 1:1 PSM of the baseline demographic data, 98 participants in the right KOA cohort (RKOAC) were successfully matched, and 117 participants in the left KOA cohort (LKOAC) were successfully matched. Furthermore, the standardized mean difference (SMD) of the matched variables in both cohorts was less than 0.25. After analyzing the outcome metrics, we found that the target knee had a significantly lower mJSW in the fourth year after baseline and a significantly greater arthroplasty rate within nine years in the exposed group than in the control group. RKOAC: mJSW (exposure: 2.6(1.1 ~ 3.6) vs. control: 3.3(2.0 ~ 4.2), P < 0.05), arthroplasty rate (exposure: 14(14.3%) vs. control: 4(4.1%), P < 0.05); LKOAC: mJSW (exposure: 3.1(2 ~ 3.9) vs. control: 3.4(2.6 ~ 4.2), P < 0.05), arthroplasty rate (exposure: 16(13.7%) vs. control: 7(6%), P < 0.05). CONCLUSIONS: Patients with knee osteoarthritis experienced greater progression of osteoarthritis when the contralateral knee was also affected.

Clinical phenotypes of comorbidities in end-stage knee osteoarthritis: a cluster analysis.

OBJECTIVES: Comorbidities, as components of these heterogeneous features, often coexist with knee osteoarthritis, and are particularly prevalent in end-stage knee osteoarthritis. Here, we attempted to identify the different clinical phenotypes of comorbidities in patients with end-stage knee osteoarthritis by cluster analysis. METHODS: A total of 421 inpatients diagnosed with end-stage knee osteoarthritis who underwent inpatient surgery were included in this cross-sectional study. 23 demographic, comorbidity, inflammatory immune and evaluation scale variables were collected. Systematic clustering after factor analysis and separate two-step cluster analysis were performed for individual comorbidity variables and all variables, respectively, to objectively identify the different clinical phenotypes of the study patients. RESULTS: Four clusters were finally identified. Cluster 1 had the largest proportion of obese patients (93.8%) and hypertension was common (71.2%). Almost all patients in cluster 2 were depressed (95.8%) and anxiety disorders (94.7%). Cluster 3 combined patients with isolated end-stage knee osteoarthritis and a few comorbidities. Cluster 4 had the highest proportion of patients with rheumatoid arthritis (58.8%). CONCLUSIONS: Patients with end-stage knee osteoarthritis may be classified into four different clinical phenotypes: "isolated end-stage knee osteoarthritis"; "obesity + hypertension"; "depression + anxiety"; and "rheumatoid arthritis", which may help guide individualized patient care and treatment strategies.

Factors associated with physical activity following total knee arthroplasty for knee osteoarthritis: a longitudinal study.

BACKGROUND: After total knee arthroplasty (TKA), patients' physical activity (PA) levels at 6 months are lower than those of healthy subjects. Few studies have investigated the factors associated with PA at 6 months after TKA by objectively measuring preoperative and postoperative PA intensity using an accelerometer and knee function using a goniometer and dynamometer. The purpose of this study was to determine the factors associated with PA levels at 6 months after TKA based on objective data. METHODS: Eighty-two patients (mean [SD] age 74.5 [6.4] years) with moderate-to-severe knee osteoarthritis (OA) who were scheduled for TKA at the Nagoya Orthopaedic and Joint Replacement Clinic from July 2018 to July 2019 were enrolled in this longitudinal study. All patients underwent evaluations of knee function, including range-of-motion and knee-extension muscle strength; knee pain; performance in the timed up-and-go test; and accelerometer-measured PA both preoperatively and 6 months postoperatively. Factors associated with PA at 6 months after TKA were assessed using a hierarchical multiple linear regression analysis adjusted for age, sex, body mass index, and presence of diabetes mellitus. RESULTS: A higher average daily step count at 6 months after TKA was significantly associated with greater preoperative knee-extension muscle strength on the operated side (ß = 0.155, p = 0.028) as well as a higher preoperative average daily step count (ß = 0.834, p < 0.001). Furthermore, average daily time spent in moderate-to-vigorous-intensity PA postoperatively was significantly associated only with time spent in moderate-to-vigorous-intensity PA preoperatively (ß = 0.723, p < 0.001). CONCLUSION: These findings indicate that a higher preoperative daily step count and greater preoperative knee-extension muscle strength on the operated side may be associated with a higher daily step count at 6 months after TKA. Factors associated with PA differed by the PA intensity level. Rehabilitation and interventions for psychosocial factors before TKA beginning when mild knee OA first occurs are expected to lead to increased PA in TKA patients.

Changes in the anteroposterior position of the femur relative to the tibia impact patient satisfaction in total knee arthroplasty.

BACKGROUND: In this study, we aimed to investigate the preoperative and postoperative anteroposterior position (AP) of the femur relative to the tibia in total knee arthroplasty (TKA) and assess the influence of change in the AP position on clinical outcomes. METHODS: We evaluated 49 knees that underwent bi-cruciate-substituted TKA using a navigation system. The preoperative and postoperative AP position of the femur relative to the tibia at maximum extension, 15°, 30°, 45°, 60°, 90°, 105°, and 120° and maximum flexion angles were calculated. The 2011 Knee Society Score was evaluated preoperatively and 1 year postoperatively. The Wilcoxon signed rank and Spearman's rank correlation tests were performed, with statistical significance set at P < 0.05. RESULTS: The postoperative AP position was significantly correlated with the preoperative AP position at each measured angle. The postoperative AP positions were statistically more anterior than those preoperatively. Furthermore, the changes in the AP position after TKA negatively correlated with the symptom (P = 0.027 at 30°, P = 0.0018 at 45°, P = 0.0003 at 60°, P = 0.01 at 90°, and P = 0.028 at 105°) and patient satisfaction (P = 0.018 at 60° and P = 0.009 at 90°) scores at 1 year postoperatively. CONCLUSION: The postoperative AP position of the femur relative to the tibia was strongly influenced by the preoperative those in TKA. Postoperative anterior deviation of the femur relative to the tibia from mid-flexion to deep flexion could worsen clinical outcomes.

Unicompartmental knee arthroplasty combined with posterior cruciate ligament reconstruction: a case report.

BACKGROUND: In this study, we present the unique case of a patient with knee osteoarthritis (OA) of the medial compartment and posterior cruciate ligament (PCL) deficiency who underwent simultaneous medial unicompartmental knee arthroplasty (UKA) and PCL reconstruction. CASE PRESENTATION: A 49-year-old male patient presented with a 1-year history of pain and instability in the left knee. The patient had previously experienced a trauma-related injury to the PCL of the left knee that was left untreated. Imaging and physical examination confirmed the presence of left medial knee OA along with PCL rupture. To address these issues, the patient underwent UKA combined with PCL reconstruction. The patient's Lysholm score was 47 before surgery and 81 three months after surgery, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was 29 before surgery and 18 three months after surgery, and the International Knee Documentation Committee (IKDC) subjective score was 56.3 before surgery and 74.7 three months after surgery. Six months after surgery, the patient's gait returned to normal, and he was able to jog. CONCLUSION: This case report presents the first instance of UKA combined with PCL reconstruction and introduces a novel treatment approach for patients suffering from medial knee OA and ligament injury.

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.

Comparison of the coverage and rotation of asymmetrical and symmetrical tibial components: a systematic review and meta-analysis.

BACKGROUND: An optimized fit of the tibial component to the resection platform and correct rotational alignment are critical for successful total knee arthroplasty (TKA). However, there remains controversy regarding the superiority of symmetric tibial component versus asymmetric tibial component. The objective of this systematic review and meta-analysis was to evaluate the current evidence for comparing the coverage and rotation of asymmetrical and symmetrical tibial component. METHODS: We searched potentially relevant studies form PubMed, Web of science, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and China National Knowledge Infrastructure (CNKI), up to 1 March 2023. Data extraction and quality assessment were performed by two independent reviewers. Meta-analysis was conducted using Review Manager 5.4. RESULTS: Sixteen articles were identified. Compared to symmetric tibial component, asymmetric tibial component increased the coverage of the proximal tibial cut surface (MD, -2.87; 95%CI, -3.45 to -2.28; P < 0.00001), improved the prevalence of tibial baseplate underhang (OR, 0.16; 95%CI, 0.07 to 0.33; P < 0.00001) and malrotation (OR, 0.13; 95%CI, 0.02 to 0.90; P = 0.04), and reduced the degree of tibial component rotation (MD, -3.11; 95%CI, -5.76 to -0.47; P = 0.02). But there was no statistical significance for improving tibial baseplate overhang (OR, 0.58; 95%CI, 0.08 to 3.97; P = 0.58). Additionally, no revision had occurred for the two tibial components in the included studies. CONCLUSION: The current evidence shows asymmetric tibial component offer advantages in terms of coverage and rotation compared with symmetric tibial component in TKA.