Tuina Intervention in Sodium Monoiodoacetate Injection-Induced Rat Model of Knee Osteoarthritis.

Knee osteoarthritis (KOA), a common degenerative joint disorder, is characterized by chronic pain and disability, which can progress to irreparable structural damage of the joint. Investigations into the link between articular cartilage, muscles, synovium, and other tissues surrounding the knee joint in KOA are of great importance. Currently, managing KOA includes lifestyle modifications, exercise, medication, and surgical interventions; however, the elucidation of the intricate mechanisms underlying KOA-related pain is still lacking. Consequently, KOA pain remains a key clinical challenge and a therapeutic priority. Tuina has been found to have a regulatory effect on the motor, immune, and endocrine systems, prompting the exploration of whether Tuina could alleviate KOA symptoms, caused by the upregulation of inflammatory factors, and further, if the inflammatory factors in skeletal muscle can augment the progression of KOA. We randomized 32 male Sprague Dawley (SD) rats (180-220 g) into four groups of eight animals each: antiPD-L1+Tuina (group A), model (group B), Tuina (group C), and sham surgery (group D). For groups A, B, and C, we injected 25 µL of sodium monoiodoacetate (MIA) solution (4 mg MIA diluted in 25 µL of sterile saline solution) into the right knee joint cavity, and for group D, the same amount of sterile physiological saline was injected. All the groups were evaluated using the least to most stressful tests (paw mechanical withdrawal threshold, paw withdrawal thermal latency, swelling of the right knee joint, Lequesne MG score, skin temperature) before injection and 2, 9, and 16 days after injection.

Preoperative Corticosteroid Injections Within 4 Weeks of Arthroscopic Shoulder Procedures Are Associated With Increased Postoperative Infection Rates.

PURPOSE: To refine the understanding of the effect of timing of corticosteroid injections (CSIs) and shoulder arthroscopy on postoperative infection. METHODS: An insurance database was used to determine all patients who underwent shoulder arthroscopy for a 5-year period with an associated preoperative ipsilateral corticosteroid injection. Patients were stratified into cohorts based on timing of preoperative CSI: (1) 0-<2 weeks, (2) 2-<4 weeks, (3) 4-<6 weeks, and (4) 6-<8 weeks. Patients were pooled to include all patients who had a CSI less than 4 weeks and those longer than 4 weeks. A cohort of patients who never had a corticosteroid injection before undergoing arthroscopy were used as a control. All patients had a follow-up of 2 years. Multivariable regression analyses were performed using R Studio with significance defined as P < .05. RESULTS: Multivariate logistic regression showed a greater odds ratio (OR) for postoperative infection in patients who received CSI 0-<2 weeks before shoulder arthroscopy at 90 days (3.10, 95% confidence interval [CI] 1.62-5.57, P < .001), 1 year (2.51, 95% CI 1.46-4.12, P < .001), and 2 years (2.08, 95% CI 1.27-3.28, P = .002) compared with the control group. Patients who received CSI 2-<4 weeks before shoulder arthroscopy had greater OR for infection at 90 days (2.26, 95% CI 1.28-3.83, P = .03), 1 year (1.82, 95% CI 1.13-2,82, P = .01), and 2 years (1.62, 95% CI 1.10-2.47, P = .012). Patients who received CSI after 4 weeks had similar ORs of infection at 90 days (OR 1.15, 95% CI 0.78-1.69, P = .48) 1 year (OR 1.18, 95% CI 0.85-1.63 P = .33), and 2 years (OR 1.09, 95% CI 0.83-1.42, P = .54), compared with the control cohort. CONCLUSIONS: The present study shows the postoperative infection risk is greatest when CSIs are given within 2 weeks of shoulder arthroscopy, whereas CSIs given within 2-<4 weeks also portend increased risk, albeit to a lesser degree. The risk of postoperative infection is not significantly increased when CSIs are given more than 1 month before surgery. LEVEL OF EVIDENCE: Level III, retrospective comparative, prognosis study.

Injections prior to hip arthroscopy are associated with increased risk of repeat hip arthroscopy at 1 and 5 years.

INTRODUCTION: Previous studies have shown that intra-articular hip injections prior to hip arthroscopy (HA) can be a helpful diagnostic tool. However, local anesthetic and corticosteroid injections can be chondrotoxic and corticosteroid injections have been shown to increase the risk of infection during subsequent surgical intervention. The purpose of this study was to evaluate whether preoperative injections adversely affect outcomes of HA using a national database. MATERIALS AND METHODS: The TriNetX database was retrospectively queried. Patients undergoing HA for femoroacetabular impingement with at least 1 year of claims runout were included in the analysis. Patients were grouped by whether they had a hip injection within 1 year prior to HA. The rates of repeat HA, total hip arthroplasty (THA), infection, osteonecrosis, and new onset hip OA at 1- and 5-years postoperatively were compared between groups. Statistical significance was assessed at α = 0.05. RESULTS: 6511 HA patients with previous injection and 1178 HA patients without previous injection were included. Patients with a previous injection were overall younger (32.3 vs. 34.7 years, p < 0.001), more likely to be female (69 vs. 48%, p < 0.001) and had a higher BMI (26.3 vs. 25.7 kg/m2, p = 0.043). At 1 and 5-years postoperatively, patients with any injection were 1.43 (p < 0.001) and 1.89 (p < 0.001) times more likely to undergo repeat HA, respectively. At 1 and 5-years postoperatively, patients who underwent a corticosteroid injection were 2.29 (p < 0.001) and 1.89 (p < 0.001) times more likely to undergo repeat HA than patients with local anesthetic injection only and 1.56 (p < 0.001) and 2.08 (p < 0.001) times more likely to undergo repeat HA than patients with no injection. CONCLUSIONS: Intraarticular hip injections prior to hip arthroscopy, particularly corticosteroid injections, are associated with increased risk of repeat hip arthroscopy at 1 and 5 years. Additional studies are needed to elucidate this risk.

Predictors of Outcomes After Lumbar Intra-Articular Facet Joint Injections and Medial Branch Blocks: A Scoping Review.

STUDY DESIGN: A scoping review. OBJECTIVE: We aimed to identify and describe the factors associated with the patient-reported response after lumbar intra-articular facet joint (FJ) injections or medial branch blocks (MBBs). SUMMARY OF BACKGROUND DATA: FJ osteoarthritis is among the most common causes of chronic low back pain. Management often includes FJ intra-articular injection and MBBs (which may be followed by radiofrequency ablation of the nerves innervating these joints). However, the success of these approaches is variable, prompting interest in identifying patient characteristics (imaging features, clinical signs, and among others) associated with response to these types of facet injections. MATERIALS AND METHODS: We performed a literature search on factors associated with patient-reported outcomes after lumbar FJ intra-articular injections or MBBs for patients with low back pain published in English or Spanish between 2000 and 2023. We excluded duplicate papers that did not describe factors associated with outcomes or those describing other interventions. We collected data on the association of these factors with patient-reported outcomes. RESULTS: Thirty-seven studies met the inclusion criteria and were analyzed. These studies evaluated factors, such as age, depression, and single photon emission computed tomography (SPECT), and among variables. Age and imaging findings of facet arthropathy were the most frequently described factors. Imaging findings of FJ arthropathy and positive SPECT were often associated with positive results after intra-articular FJ injections or MBBs. In contrast, younger age and smoking were frequently associated with less favorable clinical outcomes. CONCLUSION: Numerous factors were considered in the 37 studies included in this review. Imaging findings of facet arthropathy, duration of pain, and positive SPECT were consistently associated with favorable results after facet interventions.

Intravenous Injection of Equine Mesenchymal Stem Cells in Dogs with Articular Pain and Lameness: A Feasibility Study.

Osteoarthritis is a frequently occurring joint disorder in veterinary practice. Current treatments are focused on pain and inflammation; however, these are not able to reverse the pathological condition. Mesenchymal stem cells (MSCs) could provide an interesting alternative because of their immunomodulatory properties. The objective of this study was to evaluate the potential of a single intravenous (IV) injection of xenogeneic equine peripheral blood-derived MSCs (epbMSCs) as treatment for articular pain and lameness. Patients with chronic articular pain were injected intravenously with epbMSCs. They were evaluated at three time points (baseline and two follow-ups) by a veterinarian based on an orthopedic joint assessment and an owner canine brief pain inventory scoring. Thirty-five dogs were included in the safety and efficacy evaluation of the study. Results showed that the epbMSC therapy was well tolerated, with no treatment-related adverse events and no increase in articular heat or pain. A significant improvement in lameness, range of motion, joint effusion, pain severity, and interference scores was found 6 weeks post-treatment compared with baseline. This study demonstrates that future research on IV administration of epbMSCs is warranted to further explore its possible beneficial effects in dogs with chronic articular pain and lameness. Clinical Trial gov ID: EC_2018_002.

Preoperative intra-articular steroid injections within 3 months increase the risk of periprosthetic joint infection in total knee arthroplasty: a systematic review and meta-analysis.

OBJECTIVE: Albeit with no disease-modifying effects, intra-articular steroid injections (IASIs) are still widely used to relieve symptoms of knee osteoarthritis. Previous literature has reported conflicting results regarding the safety of IASI in terms of periprosthetic joint infection (PJI) in total knee arthroplasty (TKA). This study tried to determine whether preoperative IASIs increased the risk of PJI, with different time intervals between the injections and surgery. METHODS: A computerized search of MEDLINE, EMBASE, and Cochrane Library was conducted for studies published before October 2022, which investigated the PJI rates of patients who received IASIs before TKA and patients who did not. The primary outcome was the association between preoperative IASI and PJI in TKA. The time point from which IASIs could be applied without risking PJI was also assessed. RESULTS: Fourteen studies, with 113,032 patients in the IASI group and 256,987 patients in the control group, were included. The pooled odds ratio of PJI was 1.13 (95% confidence interval [CI] 1.00-1.27, p = 0.05), indicating no increased risk of PJI. With the time interval < 6 months, the pooled odds ratio was 1.19 (95% CI 0.99-1.43, p = 0.06). However, with the time interval < 3 months, the pooled odds ratio was 1.26 (95% CI 1.06-1.50, p < 0.01). CONCLUSION: IASI is not a safe procedure for patients who are expected to undergo TKA. The time interval between the injections and surgery was an important factor in assessing the safety of IASI. Preoperative injections that were applied within 3 months increased the risk of PJI in TKA.

Arthroscopic synovectomy versus intra-articular injection of corticosteroids for the management of refractory psoriatic or rheumatoid arthritis of the wrist: study protocol for a randomized controlled trial (ARCTIC trial).

BACKGROUND: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are inflammatory diseases that often affect the wrist and, when affected, can lead to impaired wrist function and progressive joint destruction if inadequately treated. Standard care consists primarily of disease-modifying anti-rheumatic drugs (DMARDs), often supported by systemic corticosteroids or intra-articular corticosteroid injections (IACSI). IACSI, despite their use worldwide, show poor response in a substantial group of patients. Arthroscopic synovectomy of the wrist is the surgical removal of synovitis with the goal to relieve pain and improve wrist function. The primary objective of this study is to evaluate wrist function following arthroscopic synovectomy compared to IACSI in therapy-resistant patients with rheumatoid or psoriatic arthritis. Secondary objectives include radiologic progress, disease activity, health-related quality of life, work participation and cost-effectiveness during a 1-year follow-up. METHODS: This protocol describes a prospective, randomized controlled trial. RA and PsA patients are eligible with prominent wrist synovitis objectified by a rheumatologist, not responding to at least 3 months of conventional DMARDs and naïve to biological DMARDs. For 90% power, an expected loss to follow-up of 5%, an expected difference in mean Patient-Rated Wrist Evaluation score (PRWE, range 0-100) of 11 and α = 0.05, a total sample size of 80 patients will be sufficient to detect an effect size. Patients are randomized in a 1:1 ratio for arthroscopic synovectomy with deposition of corticosteroids or for IACSI. Removed synovial tissue will be stored for an ancillary study on disease profiling. The primary outcome is wrist function, measured with the PRWE score after 3 months. Secondary outcomes include wrist mobility and grip strength, pain scores, DAS28, EQ-5D-5L, disease progression on ultrasound and radiographs, complications and secondary treatment. Additionally, a cost-effectiveness analysis will be performed, based on healthcare costs (iMCQ questionnaire) and productivity loss (iPCQ questionnaire). Follow-up will be scheduled at 3, 6 and 12 months. Patient burden is minimized by combining study visits with regular follow-ups. DISCUSSION: Persistent wrist arthritis continues to be a problem for patients with rheumatic joint disease leading to disability. This is the first randomized controlled trial to evaluate the effect, safety and feasibility of arthroscopic synovectomy of the wrist in these patients compared to IACSI. TRIAL REGISTRATION: Dutch trial registry (CCMO), NL74744.100.20. Registered on 30 November 2020. CLINICALTRIALS: gov NCT04755127. Registered after the start of inclusion on 15 February 2021.

Intra-articular corticosteroid injections are associated with a dose-dependent risk of total knee arthroplasty at 5 years.

PURPOSE: Intra-articular corticosteroid injections (CSI) are used commonly for the non-operative management of patients with knee pain. Recent literature has raised concern for chondrotoxicity of CSI. The purpose of the present study is to evaluate for any dose-dependent association between CSI in non-osteoarthritic knees and subsequent total knee arthroplasty (TKA). METHODS: The Pearl Diver database identified patients with a diagnosis of knee pain without concomitant osteoarthritis who were administered CSI over a 2-year period. Patients were compared to matched and unmatched cohorts. The primary endpoint was the incidence of TKA at 5 years. Multivariable regression analysis was used to assess CSI quantity as an independent risk factor. RESULTS: 49,443 of 986,162 (5.0%) Patients diagnosed with knee pain without concomitant knee osteoarthritis who received at least one CSI were identified. At 5 years, there was a higher incidence of TKA in the matched injection cohort relative to the non-injection matched cohort (0.26 vs 0.13%; p < 0.001) and unmatched cohort (0.26 vs. 0.10%, p < 0.001). The quantity of CSI corresponded with an increased probability of TKA at 5 years; one injection: 0.22% (OR 1.23, 95% CI [0.87-1.74], p = 0.236); two injections: 0.39% (OR 1.98 CI [1.06-3.67], p = 0.03, three or more injections: 0.49% (OR 3.22 CI [1.60-6.48], p = 0.001). The average time to TKA after one CSI was 3.03 ± 2.29 years. This time was nearly halved with three CSI (1.78 ± 0.80 years, p < 0.001). CONCLUSIONS: Intra-articular corticosteroid injections in patients without knee osteoarthritis at the time of injection are associated with a dose-dependent risk of TKA at 5 years. CSI may not be as benign of a treatment modality as previously thought.

Comparison of Femoral Triangle Block in Combination with IPACK to Local Periarticular Injection in Total Knee Arthroplasty.

OBJECTIVE: This article studied the efficacy of two different analgesic methods after unilateral primary total knee arthroplasty (TKA) to find an effective analgesic method. METHODS: A randomized, double-blind, placebo, parallel, and controlled study was performed to evaluate the benefits of combining the femoral triangle block (FTB) and the interspace between the popliteal artery and the capsule of the posterior knee (IPACK). Forty patients diagnosed with knee osteoarthritis and underwent unilateral primary TKA with FTB and IPACK were divided grouped into the experimental group, and 40 patients undergoing TKA with intra-articular cocktail analgesic mixture local injection were grouped into the control group. All patients received the patient-controlled anesthesia pump for analgesia at postoperative 48 hours. The main indexes were postoperative knee joint rest and activity pain (visual analog scale) and muscle strength of the affected limb; secondary indexes were anesthetic consumption, total morphine consumption, range of motion, and complications (such as postoperative nausea and vomiting [PONV]). RESULTS: There was no significant difference in the general data of each treatment group. Compared with the conventional group, the quadriceps muscle strength of the combined FTB and IPACK group was higher with significant statistical differences after surgery (p < 0.05). At postoperative 2, 6, 12, 24, 48, and 72 hours, active pain was better than in the conventional group (p < 0.05). Resting pain was significantly smaller than the traditional group only at postoperative 2, 6, 12, and 48 hours (p < 0.05). Morphine consumption, anesthetics consumption, and hospitalization time were lower than the conventional group, the difference being statistically significant. There were no significant differences between the two groups in postoperative wound healing, infection incidence, blood pressure, heart rate, rash, respiratory depression, deep vein thrombosis, and urinary retention. There were also no significant differences in PONV (p > 0.05). CONCLUSION: Combining FTB and IPACK significantly increased the quadriceps muscle in patients, together with relieving early pain and reducing the amount of anesthetic consumption at different postoperative intervals.

The Use of Intra-articular Platelet-Rich Plasma as a Therapeutic Intervention for Hip Osteoarthritis: A Systematic Review and Meta-analysis.

BACKGROUND: There is a cohort of patients in whom hip preservation surgery is not indicated, because they have developed signs of early osteoarthritis (OA), and nor can they have a hip replacement, as they are too early in the disease process. Management of this cohort of patients is not standardised and both pharmacological and nonpharmacological measures are utilised to reduce pain. Interventions available for early OA include intra-articular injections of steroids, viscosupplementation and more recently platelet-rich plasma (PRP). However, the use of PRP in hip OA has not yet been studied systematically. PURPOSE: To assess intra-articular PRP as a therapeutic intervention for hip OA, including the duration of efficacy, influence of dose and composition of PRP, and the incidence of adverse effects. STUDY DESIGN: A systematic review and meta-analysis; Level of evidence, 4. METHODS: We performed literature searches on the MEDLINE, EMBASE, CINAHL, WEB OF SCIENCE, COCHRANE, and SCOPUS databases, and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. Data were pooled using random-effects meta-analysis. We assessed the quality of the included studies using the methodological index for non-randomized studies instrument, with an additional assessment for randomized controlled trials with the revised Cochrane risk of bias tool for randomized trials. This is the first study to concisely collate the available data on the use of PRP in hip OA. RESULTS: Eight studies were included in the analysis, with data from a total of 331 patients. PRP significantly reduced pain compared with the baseline at multiple time points, with the greatest effect at the 1- to 2-month follow-up, but PRP significantly improved function only at the 1- to 2-month follow-up. A significantly larger reduction in pain was achieved with a single injection of PRP compared with multiple injections, a total injected dose of PRP <15 mL compared with ≥15 mL, and use of a leukocyte-poor PRP preparation compared with leukocyte-rich PRP. There were no lasting adverse effects. CONCLUSION: Low- and moderate-quality evidence suggests that PRP reduces pain and improves function at the end-point follow-up of studies compared with the baseline. Moderate-quality evidence suggests that a larger reduction in pain is achieved with a single injection of PRP compared with multiple injections, and low-quality evidence attributes a larger reduction of pain with a total injected dose of PRP <15 mL compared with ≥15 mL and using leukocyte-poor PRP compared with leukocyte-rich PRP.

Gonyautoxins 2/3 Local Periarticular Injection for Pain Management after Total Knee Arthroplasty: A Double-Blind, Randomized Study.

The purpose of this study was to compare the efficacy of periarticular infiltration of gonyautoxin 2/3 (GTX 2/3) and a mixture of levobupivacaine, ketorolac, and epinephrine for pain management after total knee arthroplasty (TKA). Forty-eight patients were randomly allocated to receive periarticular infiltration of 40 µg GTX 2/3 (n = 24) diluted in 30 mL of sodium chloride 0.9% (study group) or a combination of 300 mg of levobupivacaine, 1 mg of epinephrine, and 60 mg ketorolac (n = 24) diluted in 150 mL of sodium chloride 0.9% (control group). Intraoperative anesthetic and surgical techniques were identical for both groups. Postoperatively, all patients received patient-controlled analgesia (morphine bolus of 1 mg; lockout interval of 8 minutes), acetaminophen, and ketoprofen for 72 hours. A blinded investigator recorded morphine consumption, which was the primary outcome. Also, the range of motion (ROM) and static and dynamic pain were assessed at 6, 12, 36, and 60 hours after surgery. The incidence of adverse events, time to readiness for discharge, and length of hospital stay were also recorded. The median of total cumulative morphine consumption was 16 mg (range, 0-62 mg) in the GTX 2/3 group and 9 mg (range, 0-54 mg) in control group, which did not reach statistical difference (median test, p = 0.40). Furthermore, static and dynamic pain scores were similar at all time intervals. GTX 2/3 was inferior in range of motion at 6 and 12 hours; nevertheless, we noted no difference after 36 hours. No differences between groups were found in terms of complications, side effects, or length of hospital stay. No significant differences were found between groups in terms of breakthrough morphine requirement. However, local anesthetic use resulted in an increased ROM in the first 12 hours. This prospective randomized clinical trial shows that GTX 2/3 is a safe and efficient drug for pain control after TKA; nevertheless, more studies using GTX 2/3 with larger populations are needed to confirm the safety profile and efficiency. This is level 1 therapeutic study, randomized, double-blind clinical trial.

Do Intra-articular Corticosteroid Injections Prior to Total Knee Arthroplasty Increase Postoperative Complication Rates: A Retrospective Review.

There is conflicting literature suggesting that intra-articular corticosteroid injections before total knee arthroplasty (TKA) may lead to an increase in the rate of postoperative complications, specifically periprosthetic joint infection (PJI). Thus, this retrospective review of all TKAs performed at a large, urban hospital will add valuable evidence to help guide future patient care. After exclusion criteria, we retrospectively reviewed 417 patients who received a TKA from a group of fellowship-trained orthopaedic surgeons between 2009 and 2016 at a single academic medical center. Minimum follow-up time was 1 year. Patients were separated into two groups: those who received a preoperative intra-articular corticosteroid injection and those who did not receive an injection. Subgroups were created based on the timing of their most recent preoperative injection: 0 to 3 months, 3 to 6 months, 6 to 12 months, 12+ months, and an unknown time period. Postoperative outcomes for PJI, revision TKA, and manipulation under anesthesia (MUA) were analyzed via a Chi-square test. No statistically significant postoperative differences were observed between groups: PJI (p = 0.904), revision TKA (p = 0.206), and MUA (p = 0.163). The temporal subgroups also failed to demonstrate a statistically significant result: PJI (p = 0.348), revision TKA (p = 0.701), and MUA (p = 0.512). This study revealed no absolute or temporal association between preoperative, intra-articular corticosteroid injections, and complications after TKA. Because these injections are a commonly used treatment modality prior to TKA, further studies should be conducted on a nationwide basis to draw more concrete conclusions.

Delaying Total Knee Arthroplasty More than 4 Weeks after Intra-Articular Knee Injection Does Not Further Decrease Risk of Septic Revision.

Hyaluronic acid (HA) and corticosteroid (CS) injections are utilized in symptom management for patients with osteoarthritis. However, contamination of the joint may increase the risk of infection following total knee arthroplasty (TKA). Therefore, the purpose of this study was to examine 90-day surgical site infection (SSI) and manipulation under anesthesia (MUA) as well as up to 2-year prosthetic joint infection (PJI) in intra-articular knee injection recipients prior to TKA compared with patients who did not have knee injections. We specifically assessed (1) timing of HA and CS prior to TKA; (2) type of intra-articular knee injection; as well as (3) associated risk factors. We queried a national database to identify patients who underwent primary TKA from September 2015 to October 2020 (n = 1.5 million). Patients with prior knee injections were stratified to five cohorts: HA within 4 weeks (n = 140), HA 4 to 6 weeks prior (n = 337), CS within 4 weeks (n = 2,344), CS 4 to 6 weeks (n = 2,422), and a no injection, control, cohort prior to TKA (n = 5,000). Bivariate chi-square analyses of outcomes were conducted, and multivariate regressions were used to adjust for comorbidities and assess associated risk factors. The adjusted analysis showed a significant risk in infection for patients receiving an injection within 4 weeks of TKA (p < 0.023) and showed no difference in type of injection (p > 0.050). Additionally, SSIs were increased 1.58 times in the CS within 4 weeks of TKA cohort (p = 0.023). However, no difference in MUA risk was shown at 90-day postoperative (p > 0.212). Furthermore, tobacco use was identified as a risk factor that further increased likelihood of PJI. Intra-articular knee injection less than 4 weeks before TKA increased the risk for PJI; however, past 4 weeks did not confer infection risk. Tobacco use was identified as an associated risk factor that further increased likelihood for PJI. These results highlight the need for surgeons to wait 4 weeks between knee injection and TKA to decrease risk of septic revision.

Comparison Between Periarticular Analgesia Versus Intraarticular Injection for Effectiveness and Safety After Total Knee Arthroplasty.

PURPOSE: In most studies, local infiltration analgesia (LIA) can provide better analgesic effect in the early postoperative period, but the optimal technique is unknown. Our study was designed to evaluated the early clinical efficacy and safety of periarticular analgesia versus intraarticular injection in Total knee arthroplasty (TKA). DESIGN: A prospective study was conducted on 100 patients admitted for TKA. Subjects were divided into two groups: 50 in group A, 50 in Group B. METHODS: Patients in group A received periarticular analgesia with ropivacaine 300 mg and morphine 5 mg (the drugs were diluted with saline to 50 ml) in the periosteal borders, posterior capsule and extensor apparatus and subcutaneous tissues during surgery. After stitching of joint capsule, tranexamic acid (TXA) 2 g (20 ml) was injected into the articular cavity. Group B patients had all of the 70 mL mixture (ropivacaine 300 mg, morphine 5 mg and TXA 2 g) injected intraarticularly after stitching of the joint capsule. We assessed postoperative length of stay (LOS), knee functional outcome, pain, and complications after surgery. FINDINGS: There was no statistical difference in visual analog scale (VAS) scores for knee pain between the two groups on postoperative day (POD)1, 3, or 30 (P > .05). Mean postoperative LOS was 7.40 ± 1.98 days in Group A, compared to 8.02 ± 2.09 days in Group B (P > .05). No significant differences between groups were seen in the mean swelling ratio (P > .05), and no significant differences were found in the Hospital for Special Surgery (HSS) knee score and range of motion (ROM) at 30 days follow-up (P > .05). There was also no statistical difference in the incidence of complications (such as superficial wound infection, deep vein thrombosis (DVT) and nausea and vomiting) between the Group A and the Group B. CONCLUSIONS: In conclusion, it seems that intraarticular injection had a similar analgesic effect compared with periarticular injection when adopting a multi-modal analgesia regimen. Our results suggest that there is no obvious advantage with the use of periarticular injections compared to intraarticular injection. The authors believe that intraarticular injection may be a better technique compared with periarticular injections in the absence of a drainage tube because intraarticular injection can reduce the number of surgical steps and have similar postoperative outcomes.

Editorial Commentary: Periarticular and Intra-Articular Injections May Do the Right Thing for Patients' Pain but May Be the Wrong Thing for Their Articular Cartilage: Be Careful.

Periarticular and intra-articular injections are regularly used by orthopaedic surgeons both in the clinic and operative setting. These injections include the use of local anesthetics, nonsteroidal anti-inflammatories, steroidal anti-inflammatories, and other classes of pharmaceuticals. Local anesthetics can be injected alone or in conjunction with other pharmaceuticals to maximize pain control and to minimize narcotic use as part of a multimodal pain control algorithm. Use of intra-articular local anesthetics has been shown to improve postoperative pain scores and reduce intravenous and oral narcotic consumption and narcotic-related side effects, such as constipation, sedation, depression, respiratory depression, and long-term abuse potential. However, there have been reports of chondrolysis and other side effects from these injections. In general, it can be said that lidocaine is more chondrotoxic than bupivacaine and that methylprednisolone is more chondrotoxic when combined with either lidocaine or bupivacaine. Ropivacaine with steroid maybe less chondrotoxic, but this has yet to be established. It has been shown that ropivacaine with steroids may be toxic to chondrocytes as well as bovine tenocytes. In addition, it can be generalized that longer exposures, such as an indwelling, intra-articular catheter, are more chondrotoxic than shorter exposures, such as an intra-articular injection. Greater concentrations of lidocaine and bupivacaine (i.e., 1% vs 2% and 0.25% vs 0.5%, respectively) are more toxic to chondrocytes. Cellular morphine studies have resulted in conflicting reports of whether or not it is chondrotoxic. Both ketorolac and acetaminophen have been shown to decrease postoperative pain, but ketorolac also has been shown to be chondrotoxic in a human chondrocyte model. Doing the right thing for our patients' pain may be the wrong thing for their articular cartilage. Expansion of indications for these injections should be approached with caution.

Production of Cytotoxic Antibodies After Intra-Articular Injection of Allogeneic Synovial Membrane Mesenchymal Stem Cells With and Without LPS Administration.

Allogeneic mesenchymal stem cells (MSC) are widely used in clinical routine due to the shorter expansion time and reliability of its quality. However, some recipients can produce alloantibodies that recognize MSCs and activate the immune system, resulting in cell death. Although antibody production was already described after MSC injection, no previous studies described the immune response after intra-articular MSC injection in acute synovitis. This study aimed to evaluate the influence of inflammation on immune response after single and repeated intra-articular injections of synovial membrane MSC (SMMSC). Horses were divided in three groups: control group (AUTO) received autologous synovial membrane MSCs; whereas group two (ALLO) received allogeneic SMMSCs and group three (ALLO LPS) was submitted to acute experimental synovitis 8 h before SMMSCs injection. The procedure was repeated for all groups for 28 days. Physical and lameness evaluations and synovial fluid analysis were performed. Sera from all animals were obtained before and every 7 days after each injection up to 4 weeks, to perform microcytotoxicity assays incubating donor SMMSCs with recipients' sera. The first injection caused a mild and transient synovitis in all groups, becoming more evident and longer in ALLO and ALLO LPS groups after the second injection. Microcytotoxicity assays revealed significant antibody production as soon as 7 days after SMMSC injection in ALLO and ALLO LPS groups, and cytotoxicity scores of both groups showed no differences at any time point, being equally different from AUTO group. Although inflammation is capable of inducing MHC expression in MSCs, which enhances immune recognition, cytotoxicity scores were equally high in ALLO and ALLO LPS groups, making it difficult to determine the potentiation effect of inflammation on antibody production. Our findings suggest that inflammation does not display a pivotal role in immune recognition on first allogeneic MSC injection. In a translational way, since specific antibodies were produced against MSCs, patients that need more than one MSC injection may benefit from a first allogeneic injection followed by subsequent autologous injections.

Effectiveness of continuous femoral nerve block for pain relief after total knee arthroplasty: comparison with epidural patient-controlled analgesia and periarticular injection.

OBJECTIVE: To compare the clinical outcomes among three analgesic techniques, continuous femoral nerve block (CFNB), epidural patient-controlled analgesia (EPCA) and periarticular injection (PAI), in patients undergoing total knee arthroplasty (TKA). METHODS: This retrospective case-control study enrolled patients that underwent TKA. Visual analogue scale (VAS) pain scores, sleep disturbance, additional opioid consumption and incidence of opioid-related side-effects were assessed. RESULTS: A total of 120 patients were categorized into three groups: EPCA (group A, n = 40), PAI (group B, n = 40) and CFNB (group C, n = 40). Group C had significantly lower VAS pain scores than groups A and B at 8, 12 and 24 h after TKA. There were no significant differences in VAS pain scores among the three groups from 48 h after TKA. Sleep quality on the first day after surgery was significantly better in group C than in groups A and B. Additional opioid consumption was significantly lower in the group C than in the groups A and B. Group C showed a lower rate of opioid-related side-effects than groups A and B. CONCLUSION: CFNB was a more effective additional analgesic technique than EPCA or PAI for acute postoperative pain control within 24 h of TKA.

Intra-articular injection receipt within 3 months prior to primary total knee arthroplasty is associated with increased periprosthetic joint infection risk.

PURPOSE: This systematic review and meta-analysis analyzed the influence of pre-operative intra-articular injections (IAI) on periprosthetic joint infection (PJI) rates after primary total knee arthroplasty (TKA). METHODS: Studies published between January 1st, 2000 and May 1st, 2021 evaluating PJI rates among TKA patients with and without IAI were identified from PubMed, Cochrane Library, MEDLINE, EBSCO Host, and Google Scholar. The pooled effect of IAI on PJI risk was calculated utilizing Mantel-Haenszel (M-H) models. Sub-analysis comparisons were conducted based on the interval from IAI to TKA: 0-3 months; > 3-6 months; > 6-12 months. The Methodological Index for Non-Randomized Studies (MINORS) and the Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) tool were utilized to evaluate the quality of each included study. RESULTS: The present analysis included 12 studies reporting on 349,605 TKAs (IAI: n = 115,122; No IAI: n = 234,483). Patients receiving an IAI at any point prior to TKA (2850/115,122; 2.48%) had statistically significant increased risk of infection compared to patients not receiving IAIs (4479/234,483; 1.91%; OR: 1.14, 95% CI: 1.08-1.20; p < 0.0001). However, this finding was not demonstrated across sensitivity analyses. Receiving injections within 3 months prior to TKA was associated with increased infection risk (OR: 1.23, 95% CI: 1.14-1.31; p < 0.0001). There were no differences in infection rates when injections were given between > 3 and 6 months (OR: 0.82, 95% CI: 0.47-1.43; p = 0.49) and > 6-12 months prior to TKA (OR: 1.26, 95% CI: 0.89-1.78; p = 0.18). CONCLUSIONS: Based on the current literature, the findings of this analysis suggest that patients receiving IAI should wait at least 3 months before undergoing TKA to mitigate infection risk. Orthopaedic surgeons and patients can utilize this information when undergoing shared decision-making regarding osteoarthritis management options and timing. LEVEL OF EVIDENCE: Level III.

Comparing the Risk of Osteonecrosis of the Femoral Head Following Intra-Articular Corticosteroid and Hyaluronic Acid Injections.

BACKGROUND: Although intra-articular corticosteroid injections (CSIs) are a cornerstone in the nonoperative management of hip pathology, recent reports have raised concerns that they may cause osteonecrosis of the femoral head (ONFH). However, these studies might have been limited by nonrepresentative patient samples. Therefore, the purpose of this study was to assess the incidence of ONFH after CSI and compare it with the incidence in a similar patient population that received a non-CSI injection. METHODS: This was a retrospective propensity-matched cohort study of patients in the MarketScan database who underwent an intra-articular hip injection from 2007 to 2017. Patients receiving hip CSIs were matched 4:1 with patients receiving hip hyaluronic acid injections (HAIs) based on age, sex, geographic region, comorbidities, type of hip pathology, injection year, and baseline and follow-up time using propensity scores. The patients' first injections were identified, and the time to development of ONFH was analyzed using Kaplan-Meier curves and Cox proportional-hazards models. Patients with a history of osteonecrosis or those who received both types of injections were excluded. RESULTS: A total of 3,710 patients undergoing intra-articular hip injection were included (2,968 CSIs and 742 HAIs; mean [standard deviation] age, 53.1 [9.2] years; 55.4% men). All baseline factors were successfully matched between the groups (all p > 0.57). The estimated cumulative incidence (95% confidence interval [CI]) of ONFH for CSI and HAI patients was 2.4% (1.8% to 3.1%) versus 2.1% (1.1% to 3.5%) at 1 year and 2.9% (2.2% to 3.7%) versus 3.0% (1.7% to 4.8%) at 2 years (hazard ratio, 1.05; 95% CI, 0.59 to 1.84; p = 0.88). The results held across a range of sensitivity analyses. CONCLUSIONS: The incidence of ONFH after intra-articular hip injection was similar between patients who received CSIs and those who received HAIs. Although this study could not determine whether intra-articular injections themselves (regardless of the drug that was used) lead to ONFH, the results suggest that ONFH after CSI often may be due, in part, to the natural course of the underlying disease. Future randomized controlled trials are needed to definitively answer this question; in the interim, clinicians may be reassured that they may continue judicious use of CSIs as clinically indicated. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Cumulative Intraarticular Injections Are Not a Risk Factor for Periprosthetic Joint Infection Following total Knee Arthroplasty.

BACKGROUND: While injections within 90 days prior to total knee arthroplasty (TKA) are associated with an increased risk of periprosthetic joint infection (PJI), there is a paucity of literature regarding the impact of cumulative injections on PJI risk. This study was conducted to assess the association between cumulative corticosteroid and hyaluronic acid (HA) injections and PJI risk following TKA. METHODS: This retrospective study using an injection database included patients undergoing TKA with a minimum 1-year follow-up from 2015 to 2020. Patients with injections within 90 days prior to surgery were excluded. The sum of corticosteroid and HA injections within five years prior to TKA was recorded. The primary outcome was PJI within 90 days following TKA. Area under the curve (AUC) values were calculated for a cumulative number of injections. RESULTS: 648 knees with no injections and 672 knees with injections prior to TKA were included, among whom 243 received corticosteroids, 151 received HA, and 278 received both. No significant differences in early PJI rates existed between patients who received injections (0.60%) or not (0.93%) (P = .541). No significant differences existed in early PJI rates between patients injected with corticosteroids (0.82%), HA (0.66%), or both (0.36%) (P = .832). No cutoff number of injections was predictive for PJI. DISCUSSION: A cumulative amount of steroid or HA injections, if given more than 90 days prior to TKA, does not appear to increase the risk of PJI within 90 days postoperatively. Multiple intraarticular corticosteroid injections and HA injections may be safely administered before TKA, without increased risk for early PJI.