Association between surgeon training grade and the risk of revision following unicompartmental knee replacement: An analysis of National Joint Registry data.

BACKGROUND: Unicompartmental knee replacements (UKRs) are performed by surgeons at various stages in training with varying levels of supervision, but we do not know if this is a safe practice with comparable outcomes to consultant-performed UKR. The aim of this study was to use registry data for England and Wales to investigate the association between surgeon grade (consultant, or trainee), the senior supervision of trainees (supervised by a scrubbed consultant, or not), and the risk of revision surgery following UKR. METHODS AND FINDINGS: We conducted an observational study using prospectively collected data from the National Joint Registry for England and Wales (NJR). We included adult patients who underwent primary UKR for osteoarthritis (n = 106,206), recorded in the NJR between 2003 and 2019. Exposures were the grade of the operating surgeon (consultant, or trainee) and whether or not trainees were directly supervised by a consultant during the procedure (referred to as "supervised by a scrubbed consultant"). The primary outcome was all-cause revision surgery. The secondary outcome was the number of procedures revised for the following specific indications: aseptic loosening/lysis, infection, progression of osteoarthritis, unexplained pain, and instability. Flexible parametric survival models were adjusted for patient, operation, and healthcare setting factors. We included 106,206 UKRs in 91,626 patients, of which 4,382 (4.1%) procedures were performed by a trainee. The unadjusted cumulative probability of failure at 15 years was 17.13% (95% CI [16.44, 17.85]) for consultants, 16.42% (95% CI [14.09, 19.08]) for trainees overall, 15.98% (95% CI [13.36, 19.07]) for trainees supervised by a scrubbed consultant, and 17.32% (95% CI [13.24, 22.50]) for trainees not supervised by a scrubbed consultant. There was no association between surgeon grade and all-cause revision in either crude or adjusted models (adjusted HR = 1.01, 95% CI [0.90, 1.13]; p = 0.88). Trainees achieved comparable all-cause survival to consultants, regardless of the level of scrubbed consultant supervision (supervised: adjusted HR = 0.99, 95% CI [0.87, 1.14]; p = 0.94; unsupervised: adjusted HR = 1.03, 95% CI [0.87, 1.22]; p = 0.74). Limitations of this study relate to its observational design and include: the potential for nonrandom allocation of cases by consultants to trainees; residual confounding; and the use of the binary variable "surgeon grade," which does not capture variations in the level of experience between trainees. CONCLUSIONS: This nationwide study of UKRs with over 16 years' follow up demonstrates that trainees within the current training system in England and Wales achieve comparable all-cause implant survival to consultants. These findings support the current methods by which surgeons in England and Wales are trained to perform UKR.

Socioeconomic inequalities in patient-reported outcome measures of Dutch primary hip and knee arthroplasty patients for osteoarthritis.

OBJECTIVE: To study socio-economic inequalities in patient-reported outcomes in primary hip and knee arthroplasty (THA/TKA) patients for osteoarthritis, using two analytical techniques. METHODS: We obtained data from 44,732 THA and 30,756 TKA patients with preoperative and 12-month follow-up PROMs between 2014 and 2020 from the Dutch Arthroplasty Registry. A deprivation indicator based on neighborhood income, unemployment rate, and education level was linked and categorized into quintiles. The primary outcome measures were the EQ-5D-3L index and Oxford Hip/Knee Score (OHS/OKS) preoperative, at 12-month follow-up, and the calculated change score between these measurements. We contrasted the most and least deprived quintiles using multivariable linear regression, adjusting for patient characteristics. Concurrently, we calculated concentration indices as a non-arbitrary tool to quantify inequalities. RESULTS: Compared to the least deprived, the most deprived THA patients had poorer preoperative (EQ-5D -0.03 (95%CI -0.02, -0.04), OHS -1.26 (-0.99, -1.52)) and 12-month follow-up health (EQ-5D -0.02 (-0.01, -0.02), OHS -0.42 (-0.19, -0.65)), yet higher mean change (EQ-5D 0.02 (0.01, 0.03), OHS 0.84 (0.52, 1.16)). The most deprived TKA patients had similar results. The higher mean change among the deprived resulted from lower preoperative health in this group (confounding). After accounting for this, the most deprived patients had a lower mean change. The concentration indices showed similar inequality effects and provided information on the magnitude of inequalities over the entire socio-economic range. CONCLUSION: The most deprived THA and TKA patients have worse preoperative health, which persisted after surgery. The concentration indices allow comparison of inequalities across different outcomes (e.g., revision risk).

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.

Plasma Cartilage Acidic Protein 1 Measured by ELISA Is Associated With the Progression to Total Joint Replacement in Postmenopausal Women.

OBJECTIVE: To investigate the association of plasma cartilage acidic protein 1 (CRTAC1), a novel biochemical marker of osteoarthritis (OA), and total joint replacement (TJR) in postmenopausal women. METHODS: The association of plasma CRTAC1 with the incidence of TJR was investigated in a prospective cohort including 478 postmenopausal women. A total of 38 women underwent a TJR for OA during a median follow-up of 18 years. Every one of the TJR cases were age- and BMI (kg/m2)-matched with 2 controls with no TJR from the same cohort. Plasma CRTAC1 was measured before TJR. The association between CRTAC1 and TJR incidence was investigated by conditional logistic regression. RESULTS: Increased CRTAC1 was associated with a higher risk of TJR with an odds ratio (OR) of 1.80 (95% CI 1.11-2.92) for 1 SD increase, which remained significant after adjusting for Western Ontario and McMaster Universities Osteoarthritis Index, knee OA baseline severity (Kellgren-Lawrence grade), hip OA, and hip bone mineral density. Urinary crosslinked C-telopeptide of type II collagen (CTX-II) was also associated with a higher risk of TJR with an adjusted OR of 1.83 (95% CI 1.11-3.00). When CRTAC1 and CTX-II were included in the same model, both markers were significantly associated with TJR with similar ORs. CONCLUSION: CRTAC1 is a new risk indicator of TJR for OA in postmenopausal women. Combined with knee and hip OA and CTX-II, it may help to identify subjects at risk for TJR.

Hypercalcemia and Postoperative Joint Symptoms Following Joint Replacement for Osteoarthritis.

INTRODUCTION: Calcium metabolism dysregulation in the setting of primary hyperparathyroidism (PHPT) mediated chondrocalcinosis is implicated in joint pain, a key element in the decision regarding arthroplasty for osteoarthritis. The relationship between hypercalcemia and joint pain, before and after arthroplasty, is unknown. This study investigates the association between preoperative hypercalcemia and postoperative outcomes following total knee (TKA) and total hip arthroplasty (THA). METHODS: A retrospective chart review was conducted on patients who underwent initial elective THA or TKA. Patients with a preoperative serum calcium >10.2 mg/dL were matched (1:2-1:4) with nearest neighbor to patients with normal serum calcium. THA and TKA functional outcomes were measured at baseline and 1-y postoperatively using patient-reported Hip Disability and Osteoarthritis Outcome Scores and Knee Injury and Osteoarthritis Outcome Scores surveys. Postoperative complications, readmissions, length of stay, and functional outcome scores were compared. RESULTS: Four hundred ninety-five patients (106 hypercalcemic cases, 389 matched controls) were included. Of these, 223 patients underwent THA (46 cases; 177 controls) and 272 patients underwent TKA (61 cases; 211 controls). There were no differences in Hip Disability and Osteoarthritis Outcome Scores and Knee Injury and Osteoarthritis Outcome Scores scores, postoperative complications, readmissions, or length of stay between cases and controls. Only 19/106 (18%) hypercalcemic patients had a parathyroid hormone (PTH); of these, 9 (47%) had possible PHPT (PTH > 40). CONCLUSIONS: Patients with hypercalcemia undergoing arthroplasty have similar functional and postoperative outcomes as normocalcemic patients. As PTH was obtained in <20% of hypercalcemic cases and 50% had possible PHPT, we recommend that hypercalcemic patients undergo PHPT workup. Additional investigation is needed to determine the effect of PHPT on arthroplasty outcomes.

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.

Oxidative stress mediates associations between preoperative psychosocial phenotype and pain-related outcomes at 6 months following total knee arthroplasty: a longitudinal cohort study.

OBJECTIVE: Greater preoperative depression, anxiety, and pain catastrophizing are associated with more severe long-term pain following total knee arthroplasty (TKA). In a secondary analysis of previously reported data, we tested the hypothesis that these associations are mediated by oxidative stress (OS). DESIGN: A mixed between/within-subjects longitudinal cohort design. SETTING: A single academic medical center. SUBJECTS: Osteoarthritis patients (n = 91; 62.6% female) undergoing unilateral TKA. METHODS: We assessed depression, anxiety, and catastrophizing, as well as markers of central sensitization (widespread pain, temporal summation of pain) preoperatively. Blood samples were then obtained immediately prior to intraoperative tourniquet placement for quantification of in vivo biomarkers of systemic OS, F2-isoprostanes and isofurans. Post-TKA pain intensity (numeric rating scale worst pain [NRS], McGill Pain Questionnaire-2 [MPQ-2]) and function (PROMIS Pain Interference) were assessed at 6 months following TKA. RESULTS: Greater preoperative depression, catastrophizing, and widespread pain were associated with higher intraoperative combined OS (F2-isoprostanes+isofurans/2), which was in turn associated with higher post-TKA pain intensity and worse function (P < .05). All preoperative phenotype predictors except anxiety were correlated positively with post-TKA pain and/or function (P < .05). Bootstrapped mediation analyses revealed significant (P < .05) indirect (mediated) effects of depression (NRS Worst Pain, MPQ-2, PROMIS Pain Interference), anxiety (MPQ-2, PROMIS Pain Interference), and catastrophizing (PROMIS Pain Interference) on adverse long-term post-TKA outcomes via elevated OS. Central sensitization-related predictors demonstrated only direct effects (P < .05) on post-TKA outcomes that were independent of OS mechanisms. CONCLUSIONS: Results suggest that the adverse impact of depression, anxiety, and pain catastrophizing on post-TKA pain and functional outcomes are mediated in part by elevated OS.

Herpes Zoster Risk After Total Knee Replacement: a multicenter, propensity-score-matched cohort study in the United States.

Background: Total knee replacement (TKR) is a common surgical procedure for osteoarthritis (OA) patients. TKR may increase susceptibility to herpes zoster (HZ) by inducing immunosuppression, surgical stress, and nerve injury. However, limited data exist on the relationship between TKR and HZ. This study examined the risk of HZ over time among OA patients who underwent TKR and those who did not, using a large population-based cohort. Method: Utilizing the TriNetX research network, people with OA and underwent TKR were recruited as case group. After 1:1 propensity score matching, OA patients who never experienced TKR were included as control group. Covariates, including demographics, comorbidities, and laboratory data, were balanced using propensity score matching. A 5-year follow-up assessed the hazard ratio of incident HZ and related complications. Results: Compared to the control group, a significantly elevated risk of HZ was observed in the TKR cohort across 5-year follow-up period, with the hazard ratio of 1.223 (95% CI: 1.089-1.373). Zoster without complications presented 1.173-fold risk in TKR patients while comparing with non-TKR controls. However, most other secondary outcomes related to HZ complications-such as encephalitis, neurological involvement, ocular disease, and disseminated zoster-did not show a significant increase in risk. The risk of HZ was statistically significant for females and older adults in the TKR cohort than in the control cohort. Conclusions: OA patients who underwent TKR had an increased risk of HZ compared to those who did not receive the procedure, especially females and older adults. These findings highlight the need for HZ monitoring/prevention protocols and further research on mitigating viral reactivation after major joint surgery.

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.

Effect of Context Specificity on Response to the Shortened WOMAC Function Scale in Patients Undergoing Total Knee Arthroplasty.

OBJECTIVE: To determine, in patients undergoing total knee arthroplasty (TKA), whether increasing context specificity of selected items of the shortened version of the Western Ontario and McMaster Universities Osteoarthritis Index function (WOMAC-F) scale (ShortMAC-F) (1) enhanced the convergent validity of the ShortMAC-F with performance-based mobility measures (ii) affected mean scale score, structural validity, reliability, and interpretability. DESIGN: Secondary analysis of randomized clinical trial data. SETTING: A tertiary teaching hospital. PARTICIPANTS: Patients undergoing TKA (N=114). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The ShortMAC-F was modified by specifying the "ascending stairs" and "rising from sitting" items to enquire about difficulty in performing the tasks without reliance on compensatory strategies, whereas the modified "level walking" item enquired about difficulty in walking 400 m. Before and 12 weeks after TKA, patients completed the WOMAC-F questionnaire, modified ShortMAC-F questionnaire, knee pain scale questionnaire, sit-to-stand test, fast gait speed test, and stair climb test. Interpretability was evaluated by calculating anchor-based substantial clinical benefit estimates. RESULTS: The modified ShortMAC-F correlated significantly more strongly than ShortMAC-F or WOMAC-F with pooled performance measures (differences in correlation values, 0.12-0.14). Increasing item context specificity of the ShortMAC-F did not influence its psychometric properties of unidimensionality (comparative fit and Tucker-Lewis indices, >0.95; root mean square error of approximation, 0.05-0.08), reliability (Cronbach's α, 0.75-0.83), correlation with pain intensity (correlation values, 0.48-0.52), and substantial clinical benefit estimates (16 percentage points); however, it resulted in lower mean score (4.5-4.8 points lower). CONCLUSIONS: The modified ShortMAC-F showed sufficient measurement properties for clinical application, and it seemed more adept than WOMAC-F at correlating with performance-based measures in TKA.

The Effect of Blood Flow Restriction Exercise Prior to Total Knee Arthroplasty on Postoperative Physical Function, Lower Limb Strength and Patient-Reported Outcomes: A Randomized Controlled Trial.

The trial aimed to examine the effect of eight weeks preoperative low-load blood flow restricted resistance training (BFR-RT) on physical function, lower limb strength, and patient-reported outcomes in knee OA patients 3 and 12 months after total knee arthroplasty (TKA) compared with preoperative usual care. An assessor blinded randomized controlled trial (RCT) was conducted. Eighty-six patients scheduled for TKA who were allocated to 8 weeks BFR-RT on the affected leg 3x/week or preoperative usual care involving no exercise (CON). PRIMARY OUTCOME: 30-s sit to stand (30STS). SECONDARY OUTCOMES: Timed Up&Go, 40-m walk test (40mWT), knee range of motion (ROM) 1-repetition maximum (1RM) leg press and knee extensor strength, maximal isometric contraction (MVIC) for the knee extensors and flexors, Knee injury and Osteoarthritis Outcome Score (KOOS), and Euroqol 5-dimensions (EQ-5D-L5) questionnaire. Data were collected at baseline (12 weeks pre-surgery), ~3 days pre-surgery, 3 and 12 months postoperatively. Intention-to-treat analysis revealed no significant between-group differences in the change from baseline to 3 and 12 months postoperatively on 30STS, TUG, or 40mFWT. Significant between-group differences were observed at 3 but not 12 months postoperatively for the corresponding changes in 1RM leg press strength, 1RM knee extensor strength, and MVIC knee extensor favoring BFR-RT. No between-group differences were observed for the delta changes from baseline in knee ROM, KOOS subscales or EQ-5D-L5 at any postoperative time points. These findings suggest that preoperative BFR-RT offered no superior effects compared with usual preoperative care on postoperative physical function or patient-reported outcomes. Preoperative BFR-RT produced amplified gains in lower limb muscle strength at 3 months postoperatively. TRIAL REGISTRATION: NCT04081493.

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.