Single Intra-articular Injection Research Articles

Navigating the New EU Medical Devices Regulation: Retrospective Post-Market Follow-Up of Hyaluronic Acid Injections for Knee Osteoarthritis.

The entry into force of the new Medical Device Regulation (EU) 2017/745 highlights the need for post-market clinical follow-up to ensure the safety and efficacy throughout the life cycle of medical devices. This study evaluates the efficacy and safety of a single intra-articular hyaluronic acid injection in knee osteoarthritis in real-world conditions, over a six-month period, aligning with the summary of safety and clinical performance (SSCP) required by the new regulation. Patients over 18 years of age with knee osteoarthritis, treated with a single injection of HA (Adant® One, Meiji Pharma Spain, Spain) at a 3rd level hospital. Patients were treated and followed between January 1, 2020 and June 30, 2022. Demographic, clinical, and treatment-related data were collected, and efficacy regarding pain relief and/or function improvement was assessed using a Likert-type scale. Data were pseudo-anonymized and the comparison was performed using Fisher' or Mann Whitney' test. The study was approved by the Ethics Review Board of the Hospital Puerta de Hierro (Madrid, Spain). We followed 20 patients with knee osteoarthritis, with a mean age of 61 years, 80% women, and with a high burden of comorbidities (90%). A total of 60% of patients presented Kellgren-Lawrence grade III-IV. Four patients (20%) returned before 6 months due to lack of efficacy. Of the other patients, 65% showed a clinical response that lasted more than 12 months in 38.5% of cases. Time until medical appointment and taking concomitant medication for knee osteoarthritis were associated with better clinical response (p < 0.05). The administration of a Adant® One single intra-articular hyaluronic acid injection in knee osteoarthritis is effective, safe, and maintains the improvement over a six-month period. Our findings also emphasize the need of using standardized tools for accurate efficacy assessment and optimal patient care.

Nanoparticle-based inhibition of vascular endothelial growth factor receptors alleviates osteoarthritis pain and cartilage damage.

Osteoarthritis (OA) is characterized by cartilage damage, inflammation, and pain. Vascular endothelial growth factor receptors (VEGFRs) have been associated with OA severity, suggesting that inhibitors targeting these receptors alleviate pain (via VEGFR1) or cartilage degeneration (via VEGFR2). We have developed a nanoparticle-based formulation of pazopanib (Votrient), an FDA-approved anticancer drug that targets both VEGFR1 and VEGFR2 (Nano-PAZII). We demonstrate that a single intraarticular injection of Nano-PAZII can effectively reduce joint pain for a prolonged time without substantial side effects in two different preclinical OA rodent models involving either surgical (upon partial medial meniscectomy) or nonsurgical induction (with monoiodoacetate). The injection of Nano-PAZII blocks VEGFR1 and relieves OA pain by suppressing sensory neuronal ingrowth into the knee synovium and neuronal plasticity in the dorsal root ganglia and spinal cord. Simultaneously, the inhibition of VEGFR2 reduces cartilage degeneration. These findings provide a mechanism-based disease-modifying drug strategy that addresses both pain symptoms and cartilage loss in OA.

Treatment of osteoarthritis knee with bone marrow aspirate concentrate injection

To assess the clinical effectiveness and safety of bone marrow aspirate concentrate (BMAC) injections given intraarticularly as a potential treatment for knee osteoarthritis (OA). Data from 60 patients with knee osteoarthritis treated with BMAC injection at a single centre between December 2021 and December 2022 were retrospectively examined. We only included patients with idiopathic osteoarthritis. Post-traumatic osteoarthritis, prior knee surgery, ageless then 50 years or over 85 years, an active infection, uncontrolled diabetes mellitus, rheumatological or another systemic condition, cancer, or immunosuppressive medication use were all exclusion factors. A single-spin manual approach was used to aspirate and concentrate bone marrow from the iliac crest. The Numeric pain scale (NPS) and Oxford knee score (OKS) were used to evaluate patients both before and after the treatment. A 12-month follow-up period was used. The statistical analysis comprised a total of 60 patients. With a mean age of 67 years (range 50-85), there were 42 females and 18 males. At the end of the follow-up period, the mean NPS reduced from 8.12 to 4.31 (p&amp;#60; 0.001) and the mean OKS rise from 22.30 to 34.74 (p &amp;#60;0.001). There were no problems. A single BMAC intra-articular injection is a dependable and safe technique that improves the clinical condition of knee OA.

Safety and Efficacy of Hybrid Cooperative Complexes of Sodium Hyaluronate and Sodium Chondroitin for the Treatment of Patients with Symptomatic Knee Osteoarthritis.

Knee osteoarthritis (KOA) represents a widespread degenerative disease that causes pain and motor disability. Conservative treatments mainly focus on relieving symptoms, improving joint function, and trying to delay surgery. Safety and efficacy of hybrid cooperative complexes (2.4% sodium hyaluronate and 1.6% sodium chondroitin; HA-SC) for symptomatic KOA were investigated in a single-arm, prospective, pilot study. Patients with a visual analogue scale (VAS) pain score ≥ 4 and Kellgren-Lawrence Grade < 4 received a single intraarticular HA-SC injection. Patients with a VAS score change from baseline ≤ 1 received a second injection at day 30. Device-related adverse events (DR-AEs)/adverse events (AEs) were primary endpoints. Secondary endpoints included Western Ontario and McMaster Universities Osteoarthritis Index LK 3.1 (WOMAC LK 3.1), VAS, patient global assessment of disease status (PtGA), and patient proportion needing a second injection. Of 83 patients with KOA (Kellgren-Lawrence Grade, 2-3), 34.9% had DR-AEs at day 7. No serious DR-AEs/AEs were reported. A significant (P < 0.0001) reduction over time in VAS pain score plus WOMAC pain, stiffness, physical function limitation, and total scores was reported. Median PtGA scores indicated a 'slight improvement' at most follow-up visits. Only 18.1% of patients required a second injection. A single intraarticular HA-SC injection was safe, well-tolerated, and did not lead to major deterioration in terms of reducing knee pain, stiffness, and physical function limitation in patients with symptomatic KOA.

The In Vivo Chondrotoxicity of Single Intra-articular Injection of Local Anesthetic in Rat Cartilage.

Introduction A constant infusion of local anesthetics through pain pumps has been shown to cause chondrolysis. However, there is no general consensus regarding the safety of a single intra-articular injection of local anesthetics. In this experimental study, we examined the rat cartilage for possible histological effects after a single intra-articular administration of lidocaine or ropivacaine. Material and methods Thirty-two male Sprague-Dawley rats, weighing 250-300 grams, were divided into two groups of 16 each. We injected 0.1 ml of either lidocaine 2% (20 mg/ml) or ropivacaine 0.75% (7.5 mg/ml) into the left knee of the rats. The right knee in both groups was used as a control, and an equal amount of normal saline was injected. Each group was further divided into subgroups of four, which were euthanized after one, seven, 21, and 60 days after the initial injection. Knees were excised and prepared for histopathological analysis. A modified version of the Mankin score was used for cartilage damage evaluation. Results No difference regarding cartilage damage was detected after the examination under light microscopy between lidocaine, ropivacaine, and placebo in all specimens. Time elapsed since the initial injection did not affect the results at any time point. Conclusion A single intra-articular injection of local anesthetic did not induce any histological changes in the rat cartilage. Further research is needed to demonstrate the safety of humans.

Co-treatment with Oral Duloxetine and Intraarticular Injection of Corticosteroid plus Hyaluronic Acid Reduces Pain in the Treatment of Knee Osteoarthritis

BACKGROUND: Knee osteoarthritis (OA) is a common form of arthritis in elders which can lead to reduced daily activity and quality of life. It is important to administer a proper treatment with high efficacy and low side effects. In this study, we evaluated the efficacy of co-treatment with oral duloxetine and intraarticular (IA) injection of hyaluronic acid (HA) and corticosteroid (CS) in patients with knee OA. OBJECTIVES: This study aimed to test the hypothesis that an IA injection of CS+HA combined with duloxetine could achieve pain management superior to that of an IA injection of CS+HA alone in patients experiencing knee OA related pain. STUDY DESIGN: This study adopted a prospective, randomized, open-label blind endpoint study design. SETTING: The investigation was performed at Beijing Tiantan Hospital Affiliated with the Capital Medical University from October 2019 to December 2021. The study plan was approved by the Ethics Committee of Beijing Tiantan Hospital (KY 2019-086-02). METHODS: A total of 150 patients were randomly allocated to receive either duloxetine combined with an IA injection (n = 75) or a single IA injection alone (n = 75). All patients were followed for 24 weeks. The primary outcome was the change in the weekly 24 hours average mean pain scores, and the secondary outcomes included the proportion of patients with &gt;= 30% or &gt;= 50% pain reduction, Brief Pain Inventory (BPI) items, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, Patient Global Impression Improvement (PGI-I) ratings, hospital anxiety and depression scale (HADS) scores and adverse events (AEs). RESULTS: Patients in the experimental group had significantly greater improvement in the change of weekly mean of the 24 hours average pain scores, BPI pain severity ratings (P &lt; 0.001) and WOMAC scores (P &lt; 0.001) at the study endpoint. A significantly greater percentage of patients in the experimental group rated PGI-I of &lt;= 2 (P = 0.021) and &gt;= 50% pain reduction (P = 0.029) at 24 weeks. There was no difference in the proportion of patients with &lt;= 30% pain reduction, the HADS scores or frequency of AEs between the 2 groups. LIMITATIONS: The effectiveness and safety were examined only up to 24 weeks after treatment, and we did not perform a long-term follow-up as most previous studies have. Optimum dosage of duloxetine, as well as different molecular-weight HA, should be investigated in future studies. CONCLUSION: Patients receiving co-treatment with oral duloxetine and IA (HA+CS) injections experienced considerable improvement in pain and knee function compared to those who received an IA injection alone. KEY WORDS: Pain management, co-treatment, duloxetine, intraarticular injection, knee osteoarthritis, hyaluronic acid, corticosteroid

The Effects of Extracellular Matrix Allograft Administration on Knee Inflammation Following an Anterior Cruciate Ligament Injury in Mice

Background and Hypothesis:A human placental-derived extracellular matrix (ECM) allograft has previously been developed and is indicated by the manufacturer for reducing tissue inflammation and accelerated repair. To evaluate the efficacy of this product for reducing post-anterior cruciate ligament (ACL) injury inflammation, we used a novel murine in vivo ACL injury model. This model has previously been shown to induce significant synovitis, infrapatellar fat pad (IFP) fibrosis, and articular cartilage (AC) degradation within 2 weeks following an ACL injury. We hypothesized that intra-articular injections of the allograft would correspond with a decrease in synovitis, fibrosis, and articular cartilage degradation.&#x0D; Experimental Design or Project Methods:Ten-week-old C57BL/6J mice were randomly placed into 4 groups (n=10/group). For all mice, the right ACL was ruptured. One group served as sham controls, with a single intra-articular saline injection 24-hours following injury. The remaining three groups received 1, 2, and 6 allograft injections respectively beginning 24-hours after injury. Mice were euthanized 14 days after injury. Following euthanasia, the degree of IFP fibrosis, knee synovitis, and AC degradation were histopathologically evaluated.&#x0D; Results:Thus far, 5 mice per group have been analyzed. Within this subset of mice, those that received 6 injections demonstrated a significantly higher synovitis score (p &lt; 0.01) than the sham group. The 1-injection (p &lt; 0.01), 2-injection (p = 0.16), and 6-injection (p = 0.03) groups each displayed greater IFP fibrosis, relative to sham. No significant differences were found in AC degeneration across groups.&#x0D; Conclusion and Potential Impact:If the current results hold, following the analyses of the remaining mice, then this particular orthobiologic may not be suitable for reducing the post-ACL injury inflammatory response in mice. However, there are several limitations to this pilot study that will first need to be accounted for to confirm the lack of efficacy found.

Investigation Into the Effects of Intra-Articular Steroid on Post-Traumatic Osteoarthritis in Distal Radius Fractures: A Randomized Controlled Pilot Study

The aim of this prospective, randomized, controlled, double-blinded pilot study was to determine the rates of post-traumatic osteoarthritis and assess joint space width in the presence or absence of a single intra-articular injection of corticosteroid after an acute, intra-articular distal radius fracture (DRF). Forty patients received a single, intra-articular, radiocarpal joint injection of 4 mg of dexamethasone (DEX) (n= 19) or normal saline placebo (n= 21) within 2 weeks of a surgically or nonsurgically treated intra-articular DRF. The primary outcome measure was minimum radiocarpal joint space width (mJSW) on noncontrast computed tomography scans at 2 years postinjection. Secondary outcomes were obtained at 3 months, 6 months, 1 year, and 2 years postinjection and included Disabilities of the Arm, Shoulder, and Hand; Michigan Hand Questionnaire; Patient-Rated Wrist Evaluation; wrist range of motion; and grip strength. At 2-year follow-up, there was no difference in mean mJSW between the DEX group (2.2 mm; standard deviation, 0.6; range, 1.4-3.2) and the placebo group (2.3 mm; standard deviation, 0.7; range, 0.9-3.9). Further, there were no differences in any secondary outcome measures at any postinjection follow-up interval. Radiocarpal joint injection of corticosteroid within 2 weeks of an intra-articular DRF does not appear to affect the development of post-traumatic osteoarthritis within 2 years follow-up in a small pilot cohort. Therapeutic II.

The cost-effectiveness of adding an ultrasound corticosteroid and local anaesthetic injection to advice and education for hip osteoarthritis

Abstract Objectives Evidence for the comparative cost-effectiveness of intra-articular corticosteroid injection in people with hip osteoarthritis (OA) remains unclear. This study investigated the cost-effectiveness of best current treatment (BCT), comprising advice and education, with BCT plus a single ultrasound-guided intra-articular hip injection of 40 mg triamcinolone acetonide and 4 ml 1% lidocaine hydrochloride (BCT+US-T). Methods A trial-based cost–utility analysis of BCT+US-T compared with BCT was undertaken over 6 months. Patient-level cost data were obtained, and effectiveness was measured in terms of quality-adjusted life years (QALYs), allowing the calculation of cost per QALY gained from a UK National Health Service (NHS) perspective. Results BCT+US-T was associated with lower mean NHS costs (BCT+US-T minus BCT: −£161.6; 95% CI: −£583.95, £54.18) and small but significantly higher mean QALYs than BCT alone over 6 months (BCT+US-T minus BCT: 0.0487; 95% CI: 0.0091, 0.0886). In the base case, BCT+US-T was the most cost-effective and dominated BCT alone. Differences in total costs were driven by number of visits to NHS consultants, private physiotherapists and chiropractors, and hip surgery, which were more common with BCT alone than BCT+US-T. Conclusion Intra-articular corticosteroid injection plus BCT (BCT+US-T) for patients with hip OA results in lower costs and better outcomes, and is highly cost-effective, compared with BCT alone. Trial registration EudraCT: 2014-003412-37 (8 August 2015) and registered with Current Controlled Trials: ISRCTN 50550256 (28 July 2015). Trial protocol Full details of the trial protocol can be found in the Supplementary Appendix, available with the full text of this article at https://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-018-2153-0, doi: doi.org/10.1186/s12891-018-2153-0.

A comparative study of oral diacerein and transdermal diacerein as Novasomal gel in a model of MIA induced Osteoarthritis in rats

Background: Osteoarthritis is a chronic pathology of the joints causing disability and morbidity. Diacerein is a disease-modifying agent indicated for osteoarthritis management with enhanced performance and have much lower side effects profile than conventional non-steroidal anti-inflammatory drugs. Oral administration of Diacerein is associated with a laxative effect , thus causing treatment discontinuation. Aim: This study aimed to evaluate the activity of Diacerein novasome-based transdermal gel compared with standard oral treatment in the management of induced osteoarthritis in a rat model. Materials and methods: A single intra-articular injection of monosodium iodoacetate was administered to the left knee joint, resulting in the development of Osteoarthritis. Disease progression and the effect of both routes of Diacerein treatment were evaluated by morphological, biochemical, histological, and radiological studies. Results: Osteoarthritis was successfully induced in rats’ knee joints. Morphological studies revealed that both Diacerein treatments significantly reduced joint swelling as compared to the untreated group. The serum TNF-α and IL-1β levels were significantly lower in both Diacerein treatment groups as compared to the untreated group throughout the course of the study. Histological and radiological findings confirmed that transdermal Diacerein treatment protects against cartilage degradation like oral treatment. Conclusion: Novasomal technology proved its efficacy as a carrier for the transdermal delivery of Diacerein. The in-vivo study on an animal model of osteoarthritis showed that Diacerein transdermal gels provided sufficient pharmacological activity for the attenuation of the disease. This finding could support its use as an alternative to the standard oral treatment to avoid side effects.

The Single Intra-Articular Injection of Platelet-Rich Plasma vs. Non-Steroidal Anti-Inflammatory Drugs as Treatment Options for Canine Cruciate Ligament Rupture and Patellar Luxation.

Cranial cruciate ligament rupture (CCLR) and patellar luxation (PL) are common pathologies affecting canines. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used as a non-surgical treatment plan in these cases. Clinical usage of platelet-rich plasma (PRP) is an emerging area of interest in veterinary medicine. There is a lack of studies comparing those two different treatment methods in veterinary medicine. The main purpose of this study was to evaluate and compare the use of oral NSAIDs and single intra-articular injection of PRP on treatment outcomes in cases of canine CCLR and PL. Dogs diagnosed with CCRL (n = 12) and PL (n = 10) were subgrouped by the severity of pathologies and administered treatment: half of the CCRL and PL groups were orally administered NSAIDs and supplements for 14 days, and the other half received a single intra-articular PRP injection into affected stifle joint. We measured serum TNF-α levels and clinical outcomes (lameness scores, painfulness to manipulations, goniometry of stifle joint in flexion and extension, and muscle strength) before treatment, at day 14 and day 28 of treatment. The results of TNF-α concentration indicates a significant difference between groups of differently treated partial CCLR groups on d14 (p = 0.006). Results of group CCLR-P1 on d14 were decreased, while results of group CCLR-P2 on d14 were increased. When comparing TNF-α concentration between all CCLR cases treated with NSAIDs and treated with PRP, there was a significant difference between those groups on d14 (p = 0.001). The results of TNF-α concentration indicates a significant difference between groups of differently treated PL-III on d28 (p = 0.036). Results of group PL-III1 indicate growth of TNF-α concentration, while at the same d28, results of group PL-III2 indicate decreased levels of cytokine, comparing results between the subgroups at the same time point and within subgroups from baseline. Results indicate a significant difference in muscle strength between group CCLR-P1 and group CCLR-P2 on d28 (p = 0.007), indicating an increment in muscle strength in group CCLR-P1 up to d14 and its reduction up to d28, and muscle strength of group CCLR-P2 increasing up to d28. When comparing the muscle strength between all CCLR cases treated with NSAIDs and treated with PRP, there was a significant difference between those groups on d28 (p = 0.007). In conclusion, a single intra-articular injection of PRP has a superior effect on management of inflammatory processes, has better clinical outcomes, and longer duration of action than oral NSAIDs, in the treatment of canine CCRL or PL.

POLYACRYLAMIDE HYDROGEL VERSUS HYALURONIC ACID IN KNEE OSTEOARTHRITIS: A SUBGROUP ANALYSIS OF A RANDOMIZED STUDY

AbstractIntroductionThe effectiveness of single intra-articular injections of polyacrylamide hydrogel (iPAAG) and hyaluronic acid (HA) was compared in subgroups of participants from an RCT based on baseline age, BMI or Kellgren-Lawrence (KL) grade.Methodology239 participants were randomised to 6 mL iPAAG (Arthrosamid; n=119) or 6 mL HA (Synvisc-One; n=120). Participants continued analgesics (except 48 hours prior to visits) and non-pharmacological therapy. Topical therapies and intra-articular corticosteroids were not allowed. Pre-specified subgroup analyses (age: &lt;70 years, ≥70 years; BMI: normal, overweight, obese; KL grade: 2, 3, 4, 2–3) of change from baseline in WOMAC pain subscale at 52 weeks were based on the least squares means for the treatment-by-week interaction effect using a mixed model for repeated measurement with a restricted maximum likelihood-based approach.ResultsAcross all patients, change from baseline in WOMAC pain subscale in the iPAAG group was non-inferior to HA at 26 weeks and approached superiority (p=0.0572) at 52 weeks. Treatment differences for change from baseline in WOMAC pain subscale in favour of iPAAG over HA were statistically significant for the age &lt;70 years (p=0.019), BMI normal (p=0.011) and KL grade 2–3 (p=0.033) subgroups. Treatment differences for all other subgroups favoured iPAAG, except for KL grade 4 which favoured HA, without reaching statistical significance.ConclusioniPAAG approached superiority to HA across all participants at 52weeks, but demonstrated statistical superiority in participants with normal BMI, participants &lt;70 years old or participants with KL score 2–3. iPAAG represents a useful alternative to HA for the treatment of knee OA.

Honey improves radiographic features of monosodium iodoacetate-induced stifle (knee) joint osteoarthritis in a rat model

Osteoarthritis (OA) is the most common form of joint disease with over half of all people older than 65 years demonstrating radiographic changes of osteoarthritis in the knees. Honey is known to contain bioactive compounds that exert chondroprotective effects by counteracting the homeostatic dysregulation of the joint. However, its effect on the radiographic features of osteoarthritis has not been proven. This study was carried out to evaluate the effect of honey on radiographic features of monosodium iodoacetate (MIA)- induced knee osteoarthritis in female Wistar rats. Thirty female Wistar rats were randomly divided into five groups of six animals each. Animals in group one were healthy (control) rats, while animals in groups two to five were subjected to experimental osteoarthritis of the right knee joint induced by a single intra-articular injection of 1mg of MIA. The animals in groups two, three, four, and five were treated with normal saline (1ml/kg b. w.), arthocare (glucosamine/chondroitin sulfate 6.67/8.33mg/kg b. w.), low dose honey (250mg/kg b. w.) and high dose honey (1,000mg/kg b. w.) respectively. All treatments were administered orally once daily using an oral cannula for twenty-one days. All animals were subjected to radiographic assessment of the right knee joint before and after induction of OA, and after treatment. High and low-dose honey reversed the loss of joint space; sclerosis of the tibial plateau, medial, and lateral femoral condyles, when compared to the arthocare-treated and untreated groups. In conclusion, honey improved radiographic features of knee osteoarthritis in a rat model induced by monosodium iodoacetate.

Efficacy and Safety of Stempeucel in Osteoarthritis of the Knee: A Phase 3 Randomized, Double-Blind, Multicenter, Placebo-Controlled Study

Background: Osteoarthritis is a chronic, progressive, and degenerative condition with limited therapy options. Recently, biologic therapies have been an evolving option for the management of osteoarthritis. Purpose: To assess whether allogenic mesenchymal stromal cells (MSCs) have the potential to improve functional parameters and induce cartilage regeneration in patients with osteoarthritis. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 146 patients with grade 2 and 3 osteoarthritis were randomized to either an MSC group or placebo group with a ratio of 1:1. There were 73 patients per group who received either a single intra-articular injection of bone marrow–derived MSCs (BMMSCs; 25 million cells) or placebo, followed by 20 mg per 2 mL of hyaluronic acid under ultrasound guidance. The primary endpoint was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score. The secondary endpoints were WOMAC subscores for pain, stiffness, and physical function; the visual analog scale score for pain; and magnetic resonance imaging findings using T2 mapping and cartilage volume. Results: Overall, 65 patients from the BMMSC group and 68 patients from the placebo group completed 12-month follow-up. The BMMSC group showed significant improvements in the WOMAC total score compared with the placebo group at 6 and 12 months (percentage change: −23.64% [95% CI, −32.88 to −14.40] at 6 months and −45.60% [95% CI, −55.97 to −35.23] at 12 months P < .001; percentage change, −44.3%). BMMSCs significantly improved WOMAC pain, stiffness, and physical function subscores as well as visual analog scale scores at 6 and 12 months (P < .001). T2 mapping showed that there was no worsening of deep cartilage in the medial femorotibial compartment of the knee in the BMMSC group at 12-month follow-up, whereas in the placebo group, there was significant and gradual worsening of cartilage (P < .001). Cartilage volume did not change significantly in the BMMSC group. There were 5 adverse events that were possibly/probably related to the study drug and consisted of injection-site swelling and pain, which improved within a few days. Conclusion: In this small randomized trial, BMMSCs proved to be safe and effective for the treatment of grade 2 and 3 osteoarthritis. The intervention was simple and easy to administer, provided sustained relief of pain and stiffness, improved physical function, and prevented worsening of cartilage quality for ≥12 months. Registration: CTRI/2018/09/015785 (National Institutes of Health and Clinical Trials Registry–India).

Mid- to long-term success rate and functional outcomes of acromioclavicular injections in patients with acromioclavicular osteoarthritis.

Acromioclavicular (AC) osteoarthritis (OA) is a frequent pathology of the shoulder in elderly patients. Drug injection plays an important role in treatment of AC OA. Literature has demonstrated excellent short-term results regarding shoulder function and pain. However, mid- to long-term results are lacking. The aim of this study was to assess the efficacy of a single intra-articular AC injection in patients with AC OA and to identify predictive factors for success. A retrospective study was performed to analyze success rate, shoulder function, and pain perception after a single intra-articular injection in patients with AC OA. Success was defined as the absence of reinterventions such as additional injection or surgery. Outcome measures were 1-year success rate and clinical outcome scores of Numeric Rating Scale (NRS) for pain, Oxford Shoulder Score, and Subjective Shoulder Value. Ninety-eight patients participated in this study. At a median final follow-up of 0.8 years (interquartile range, 0-6), 57 of these patients (58%) had undergone a reintervention. The 1-year success rate was 47% (95% confidence interval, 37%-57%), with NRS at rest as the sole factor significantly associated with success. Thirty patients not requiring reintervention reported significant improvement from baseline for all reported outcome measures at final follow-up. AC injections offer a 1-year success rate of 47%. The AC injection produces good mid- to long-term clinical outcomes regarding shoulder function, quality of life, and pain perception in one-third of patients. Further research is essential to analyze mid- to longterm outcomes of AC injections. Level of evidence: Level IV.

Reversing inflammatory microenvironment by a single intra-articular injection of multi-stimulus responsive lipogel to relieve rheumatoid arthritis and promote joint repair.

Rheumatoid arthritis (RA) is a common chronic disease dominated by inflammatory synovitis, which is characterized with hyperplastic synovium, up-regulated matrix metalloproteinase (MMP) expression, hypoxic joint cavity and excessive reactive oxygen species (ROS) accumulation. Such local adverse microenvironment in RA joints further exacerbates the infiltration of synovial inflammatory cells, especially M1-type macrophages. Regulating intra-articular pathological conditions, eliminating excess M1 macrophages or converting them to an anti-inflammatory M2 phenotype may break the vicious progression circle. Herein, we develop a multi-stimulus responsive lipogel as effective platform to relieve RA symptoms and promote articular cartilage recovery via reversing its inflammatory microenvironment. The injectable lipogel is fabricated by loading polydopamine nanoparticles and methotrexate into a thermosensitive gel, and intra-articularly injected to form the therapeutic depot (PDA/MTX@TSG) in situ. The gel degrades slowly under esterase hydrolysis, and maintains sustained drug release in physiological conditions. Meanwhile, it can 1) induce a reversible gel-sol phase transition upon mild photothermal treatment (external NIR light control), and 2) specifically respond to MMP-rich RA microenvironment (internal enzymatic hydrolysis effect). Such stimulus-responsive system can deliver therapeutic components in a controllable manner, and significantly reverse adverse inflammatory microenvironment of RA joints through ROS eliminating, hypoxia alleviating, and M1-M2 macrophage polarization effects. Animal experiments indicate that observable RA relief and joint repair are realized after a single lipogel injection combined with NIR irradiation. Our study highlights the importance of altering local RA microenvironment via anti-inflammatory macrophage polarization, and therefore presents a potent therapeutic strategy for RA treatment in clinical intervention.

Escinosome thermosensitive gel optimizes efficacy of CAI-CORM in a rat model of rheumatoid arthritis.

Rheumatoid arthritis is among the most common disabling diseases associated with chronic inflammation. The efficacy of the current therapeutic strategies is limited; therefore, new pharmacological agents and formulation approaches are urgently needed. In this work, we developed a thermosensitive gel incorporating escinosomes, innovative nanovesicles made of escin, stabilized with 10% of tween 20 and loaded with a Carbonic Anhydrase Inhibitor (CAI) bearing a Carbon Monoxide Releasing Moiety (CORM) (i.e., CAI-CORM 1), previously synthesized by some of the authors as a new potent pain-relieving agent. The light scattering analysis of the developed formulation showed optimal physical parameters, while the chromatographic analysis allowed the quantification of the encapsulation efficiency (90.1 ± 5.91 and 91.6 ± 8.46 for CAI-CORM 1 and escin, respectively). The thermosensitive gel, formulated using 23% w/v of poloxamer 407, had a sol-gel transition time of 40 s and good syringeability. Its stability in simulated synovial fluid (SSF) was morphologically evaluated by electron microscopy. Nanovesicles were physically stable in contact with the medium for two weeks, maintaining their original dimensions and spherical shape. The viscosity increased by about 30- to 100-fold with the temperature change from 25 °C to 37 °C. The gel erosion in SSF occurred within 9 h (88.2 ± 0.743%), and the drug's passive diffusion from escinosomes lasted 72 h, allowing a potential sustained therapeutic effect. The efficacy of a single intra-articular injection of the gel containing escinosomes loaded with CAI-CORM 1 (3 mg/mL; 30 μL, CAI-CORM 1 formulation) and the gel containing unloaded escinosomes (30 μL, blank formulation) was evaluated in a rat model of Complete Freund's Adjuvant (CFA)-induced rheumatoid arthritis. CAI-CORM 1 formulation was assessed to counteract mechanical hyperalgesia, spontaneous pain, and motor impairments on days 7 and 14 after treatment. The histological evaluation of the joints stressed the improvement of several morphological parameters in CFA + CAI-CORM 1 formulation-treated rats. In conclusion, the hybrid molecule CAI-CORM 1 formulated in escinosome-based thermosensitive gel could represent a new valid approach for managing rheumatoid arthritis.

Derivation of a clinical decision rule for a bone marrow aspirate concentrate injection in knee osteoarthritis.

Aim: To develop a simple clinical decision rule (CDR) to identify people with knee osteoarthritis who are likely or unlikely to benefit from bone marrow aspirate concentrate (BMAC) injection. Materials & methods: A total of 92 people with clinical and radiographic evidence of refractory knee osteoarthritis received a single intra-articular (IA) BMAC injection. Multiple logistic regression analysis was used to determine which combination of risk factors predicted BMAC responsiveness. A responder was defined as a person whose knee pain improved more than 15% from baseline 6months postprocedure. Results: The CDR demonstrated that those with lower pain levels, or high pain levels with previous surgery, could be predicted to benefit from a single IA BMAC injection. Conclusion: A simple CDR containing three variables predicted responsiveness to a single IA knee BMAC injection with high accuracy. Further validation of the CDR is required prior to routine use in clinical practice.

Circulating miR-146b and miR-27b are efficient biomarkers for early diagnosis of Equidae osteoarthritis

One of the most orthopedic problems seen in the equine is osteoarthritis (OA). The present study tracks some biochemical, epigenetic, and transcriptomic factors along different stages of monoiodoacetate (MIA) induced OA in donkeys in serum and synovial fluid. The aim of the study was the detection of sensitive noninvasive early biomarkers. OA was induced by a single intra-articular injection of 25 mg of MIA into the left radiocarpal joint of nine donkeys. Serum and synovial samples were taken at zero-day and different intervals for assessment of total GAGs and CS levels as well as miR-146b, miR-27b, TRAF-6, and COL10A1 gene expression. The results showed that the total GAGs and CS levels increased in different stages of OA. The level of expression of both miR-146b and miR-27b were upregulated as OA progressed and then downregulated at late stages. TRAF-6 gene was upregulated at the late stage while synovial fluid COL10A1 was over-expressed at the early stage of OA and then decreased at the late stages (P < 0.05). In conclusion, both miR-146b and miR-27b together with COL10A1 could be used as promising noninvasive biomarkers for the very early diagnosis of OA.

Comparison of Functional Outcome of Single Versus Multiple Intra-articular Platelet-Rich Plasma Injection for Early Osteoarthritis Knee.

Background Osteoarthritis (OA) is a leading cause of pain and disability and has a negative impact on patients' quality of life. Platelet-rich plasma (PRP) has emerged as a promising treatment for various orthopaedic conditions, such as tendinopathies, nonunion, and arthritis of the knee. We sought to determine whether a single intra-articular platelet-rich plasma injection has better functional and pain outcomes when compared with multiple (two) articular platelet-rich plasma injections given in the early stages of OA of the knee, measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and the visual analogue scale for pain (VAS) at the sixth week, third month, and sixth month. Materials and methods The prospective observational study was conducted among patients diagnosed with early OA who presented to the Department of Orthopaedics, R. L. Jalappa Hospital and Research Centre, Kolar, Karnataka, India, between January 2020 and June 2021. A total of 64 patients were divided into: (i) S-PRP group (34 patients), which received a single PRP injection, and (ii) M-PRP group (30 patients), which received multiple (two) PRP injections, one on presentation and the second in the thirdmonth. VAS and WOMAC scores to assess functional outcomes were used at the first visit before the intervention and at the sixth week, third month, and sixth month. Results The average age of the patients was 55.26 years in the S-PRP group and 51.13 years in the M-PRP group. Both genders were equal among study participants in the M-PRP group, but 79.4% were females in the S-PRP group.In the S-PRP group, 74% had grade II OA and 26% had grade I OA. In the M-PRP group, 60% had grade II OA and the remaining 40% had grade I OA. The decreasing trend of pain and functional limitation, which was measured by VAS and WOMAC, respectively, was observed in both groups at pre-injection, sixth week, third month, and sixth month. These differences were statistically significant. The mean difference in VAS score between the pre-injection period and at six months was 4 in the S-PRP group, whereas it was 5.77 in the M-PRP group, and this was statistically significant (p-value = 0.001). Thus, multiple PRP injections have a greater response to pain reduction when compared to single PRP injections, according to the VAS score.According to the WOMAC score, there is no statistically significant difference in the treatment response with PRP injection between the S-PRP and M-PRP groups at any follow-up period. Conclusion According to the VAS score, single PRP injections have a lower pain score than multiple PRP injections until three months of follow-up, while at six months, single PRP injections have no better effect than multiple PRP injections. But multiple PRP injections have a higher reduction in the intensity of pain when compared to single PRP injections during the follow-up period. According to the WOMAC score, there is no statistically significant difference in the treatment response with PRP injection between S-PRP and M-PRP groups.