Effects of Intra-Articular Triamcinolone Injection on Adhesive Capsulitis after Breast Cancer Surgery.

PURPOSE: To investigate the effects of intra-articular glenohumeral joint triamcinolone injection in treating secondary adhesive capsulitis after breast cancer surgery. METHODS: This study prospectively enrolled 37 participants, including 22 in the breast cancer surgery group and 15 in the idiopathic group. All participants received intra-articular glenohumeral joint triamcinolone injection in the affected shoulder joint. The clinical outcomes included the Shoulder Pain and Disability Index (SPADI), passive range of motion (PROM), and pain intensity on the Numeric Rating Scale (NRS), which were evaluated before the intervention and 1, 3, and 6 months after. The primary outcome of this study was the mean difference in the total SPADI from baseline to 6 months after the intervention. RESULTS: The mean differences in the total SPADI scores from baseline to 6 months after the intervention were 36.2 ± 16.4 and 47.9 ± 15.2 in the breast cancer surgery group and the idiopathic group, respectively. There was no significant difference between the two groups (p = 0.1495). However, the improvements in the SPADI pain subscale at the 3- and 6-month follow-up visits (-31.2 vs. -48.8, p = 0.042; -34.1 vs. -50.7, p = 0.0006) and the PROM of abduction at the 3-month follow-up (52.4 vs. 70.3, p = 0.0072) were inferior in the breast cancer surgery group compared to the idiopathic group. There were no adverse events in either group. CONCLUSION: Intra-articular triamcinolone injection is an effective and safe treatment option for adhesive capsulitis after breast cancer surgery; however, it has less effect than for idiopathic adhesive capsulitis.

Synovial mesenchymal stem cells secrete more lubricin than adipose mesenchymal stem cells after injection into rat osteoarthritis knees.

Intra-articular injection of mesenchymal stem cells (MSCs) is envisioned as a solution for knee osteoarthritis (OA). Although synovial MSCs (SyMSCs) are promising for cartilage regeneration, the clinical choice is usually adipose MSCs (AdMSCs). However, the similarities/differences in the mode of action between SyMSCs and AdMSCs remain unclear. Here, we compared factors secreted by human SyMSCs and AdMSCs after injection into OA knees. Human SyMSCs or AdMSCs were injected into the knees of rat partial meniscectomy models. The next day, the knee joints were collected to analyze the distribution of injected MSCs and transcriptome changes in the human MSCs and rat synovium. Non-injected MSCs were mixed with rat synovium as a control. After injection, no difference was apparent in intra-articular distribution of the SyMSCs or AdMSCs. RNA sequencing demonstrated an enrichment of cytokine-cytokine receptor interaction-related genes in both human SyMSCs and AdMSCs after injection. Differentially expressed genes (DEGs) specific to SyMSCs were associated with cartilage matrix synthesis and homeostasis. PCR analysis of the matrisome-related DEGs showed significantly higher expression of PRG4 in SyMSCs than in AdMSCs after injection. Immunostaining also confirmed a significantly greater expression of lubricin by SyMSCs than by AdMSCs. These findings indicate that SyMSCs will be a more promising treatment for OA.

Long-acting bulleyaconitine A microspheres via intra-articular delivery for multidimensional therapy of rheumatoid arthritis.

Bulleyaconitine A (BLA) is a promising candidate for treating rheumatoid arthritis (RA) with diverse pharmacological activities, including anti-inflammatory, analgesic and bone repair. Herein, the long-acting bulleyaconitine A microspheres (BLA-MS) were developed to treat RA comprehensively by forming drug reservoirs in joint cavities. The BLA-MS were prepared by emulsion/solvent evaporation method. The particle size and distribution were assessed by SEM. The crystalline state was investigated by DSC and PXRD. The drug loading (DL), encapsulation efficiency (EE) and cumulative release in vitro were determined by HPLC. The DL and EE were 23.93 ± 0.38 % and 95.73 ± 1.56 % respectively, and the cumulative release was up to 69 days with a stable release curve. The pharmacodynamic results in collagen induced arthritis (CIA) rats showed a noticeable reduction in paw thickness (5.66 ± 0.32 mm), and the decreasing expression level of PGE2, TNF-α and IL-6 which diminished the infiltration of inflammatory cells, thereby alleviating the progression of erosion and repairing the damaged bones (BV/TV (Bone Volume / Total Volume): 81.97 %, BS/BV (Bone Surface / Bone Volume): 6.08 mm-1). In conclusion, intra-articular injection of BLA-MS should have a promising application in the treatment of RA and may achieve clinical transformation in the future.

Postoperative Infection Following Hip Arthroscopy in Patients Receiving Preoperative Intra-articular Injections: A Systematic Review and Meta-Analysis.

Intra-articular injections prior to hip arthroscopy are often used to diagnose and conservatively manage hip pathologies, such as femoroacetabular impingement, labral tears, and chondral lesions. As a diagnostic tool, the relief of hip pain following an intra-articular injection helps pinpoint the primary source of pain and assists surgeons in recommending arthroscopic intervention for underlying intra-articular pathologies. However, when injections are not sufficiently spaced apart in time prior to hip arthroscopy, there is an elevated risk of postoperative infection. This systematic review aims to assess whether preoperative intra-articular injections prior to hip arthroscopy are associated with an increased risk of postoperative infection and to determine the safety timeframe for administering such injections prior to the procedure. A comprehensive search was conducted in the PubMed, Embase, and Cochrane Library databases to identify studies examining the relationship between preoperative intra-articular injections and postoperative infection following hip arthroscopy. A meta-analysis was conducted to compare the risk of infection between patients who received injections prior to hip arthroscopy at varying intervals and those who did not receive any preoperative injections. Five studies were included (four level III and one level IV), which consisted of 58,576 patients (58.4% female). Injections administered anytime prior to hip arthroscopy posed a significantly higher risk of infection compared to no history of prior injections (risk ratio: 1.45, 95% confidence interval: 1.14-1.85, P = 0.003). However, upon subanalysis, the risk of infection was significantly higher among patients who received injections within three months prior to hip arthroscopy compared to those who did not receive injections (risk ratio: 1.55, 95% confidence interval: 1.19-2.01, P = 0.001). Additionally, no significant difference in infection risk was observed when injections were administered more than three months before hip arthroscopy compared to no injections (risk ratio: 1.05, 95% confidence interval: 0.56-1.99, P = 0.87). The findings suggest that patients undergoing hip arthroscopy who have previously received intra-articular injections may face a statistically higher risk of postoperative infection, particularly when the injection is administered within three months prior to hip arthroscopy. Consequently, surgeons should exercise caution and avoid administering intra-articular injections to patients scheduled for hip arthroscopy within the subsequent three months to mitigate the increased risk of infection.

Time to Total Knee Arthroplasty (TKA) Post Intra-Articular Injection.

Background: Disease-modifying treatments are not currently developed to target the underlying causes of knee osteoarthritis (KOA). Corticosteroids (CS), hyaluronic acid (HA), and platelet-rich plasma (PRP) intra-articular (IA) injections are commonly used for patients that do not respond to non-pharmacological treatments, oral nonsteroidal anti-inflammatory, or pain medications to address solely KOA symptoms. Utilizing TKA as an endpoint in the KOA disease progression provides a basis to determine efficacy of this treatment pathway. The primary objective is to evaluate a large national database to determine the time between first injection and total knee arthroplasty in patients solely administered intra-articular IA, CS, and HA. Methods: A retrospective query was performed on a national, all-payer claims database (PearlDiver, Colorado Springs, CO, USA), a composite of over 160 million Health Insurance Portability and Accountability Act compliant orthopedic records across all states and territories of the United States spanning 2016 to 2022. The database was queried to produce three distinct cohorts for analysis (PRP, HA, and CS). A 4:1 case match was conducted to compare cohorts receiving a subsequent TKA. Kaplan-Meier survival analysis analyzed the TKA-free survival of patients within each group at 6 months and 1 to 4 years. The log-rank test was performed for comparisons between survival cohorts. Results: The PRP cohort had a total population of 3240 patients, of which 71 (2.2%) received a subsequent TKA. The corticosteroid cohort had a total population of 1,382,572, of which 81,271 (5.9%) received a subsequent TKA. The HA cohort had a total population of 164,000, of which 13,044 (8.0%) received a subsequent TKA. Due to the low population within the PRP group, this group was excluded from comparison. The mean time to TKA from first injection in the HA group was 377.8 days, while in the corticosteroid group it was 370.0 days. The proportions of TKA-free survival for CS and HA when compared at 4 years post-injection was similar between groups (p = 0.05). Discussion and Conclusion: Patients that received only IA-corticosteroids or IA-hyaluronic acid had a similar length of time between the first injection and the total knee arthroplasty associated with the injected joint. This evidence provides information for clinicians and patients alike when contemplating these non-surgical injection modalities for KOA. The similarity observed between these treatments supports the need for future research to determine whether there is any potential for reduction in healthcare costs for KOA treatment prior to TKA.

Advancements in pH-Responsive nanoparticles for osteoarthritis treatment: Opportunities and challenges.

Osteoarthritis (OA) is a degenerative disease linked to aging and obesity. The global aging population has led to an increasing number of OA patients, imposing a significant economic burden on society. Traditional drugs treatment methods often fail to achieve satisfactory outcomes. With the rapid advancement of nanomaterial delivery systems, numerous studies have focused on utilizing nanomaterials as carriers to achieve efficient OA treatment by effectively loading and delivering bioactive ingredients (e.g., drugs, nucleic acids) tailored to the unique pathological conditions, such as the weakly acidic microenvironment of synovial fluid in OA patients. This review highlights the latest advancements in the use of pH-responsive nanoparticles for OA treatment, emphasizing the principle of targeted drug delivery leveraging the acidic microenvironment of inflamed joints. It further discusses the composition, synthesis, response mechanism, target selection, application, and recent research findings of nanoparticles, while also addressing the challenges and future directions in this promising field.

Adding Dexmedetomidine to Intra-articular Local Anesthetics Results in Prolonged Analgesia after Knee Arthroscopy: A Systematic Review and Meta-Analysis.

PURPOSE: This systematic review and meta-analysis aims to assess the efficacy and safety of dexmedetomidine as an adjuvant to intra-articular (IA) injections of local anesthetics (LA) in adult patients undergoing knee arthroscopy. METHODS: We searched MEDLINE, Embase, and Cochrane Library for randomized controlled trials (RCTs) comparing IA dexmedetomidine plus LA versus LA alone for knee arthroscopy in adults. We used the DerSimonian and Laird random-effects model for all outcomes, and conducted a sensitivity analysis with the leave-one-out method, as well as a subgroup analysis for the type of LA. We used R version 4.1.2 for all statistical analyses. RESULTS: We included 16 RCT encompassing 799 patients, of whom 49.8% received IA dexmedetomidine. In the pooled analysis, time to first analgesia rescue was prolonged in almost 4 hours with the use of dexmedetomidine (MD 229 min; p<0.001). We found statistically significant differences favoring dexmedetomidine in pain scores at rest and movement throughout the first 2, 6, 12 and 24 hours postoperatively (p<0.001). Although the mean difference (MD) ranged from -0.3 to -0.9 cm, corresponding to a 3 to 9% reduction in pain scores, this change is not clinically significant when compared to the minimal clinically important difference (MCID). Additionally, the intervention group showed a statistically significant reduction in cumulative opioid consumption over 24 hours (MD -4.5 mg; p<0.001). However, this reduction did not meet the threshold for the MCID. There was no difference between groups on the incidence of hypotension (p=0.190), bradycardia (p=0.430) and postoperative nausea and vomiting (p=0.550). CONCLUSIONS: Adding dexmedetomidine to LA in IA injections for knee arthroscopy significantly extended analgesia duration. Additionally, it lowered pain scores and opioid use, although these effects did not reach the MCID. Furthermore, this addition did not increase the risk of adverse events.

Chondrotoxicity of Intra-Articular Injection Treatment: A Scoping Review.

The purpose of this scoping review was to identify possible chondrotoxic effects caused by drugs usually used for intra-articular injections. PubMed, Scopus, Web of Science and Cochrane were searched. Inclusion criteria required randomized controlled trials written in English that evaluate the toxic effect that damages the cartilage. The literature search resulted in 185 unique articles. 133 full-text articles were screened for inclusion, of which 65 were included. Corticosteroids, with the exception of triamcinolone, along with local anaesthetics, potentially excluding ropivacaine and liposomal bupivacaine, and nonsteroidal anti-inflammatory drugs, exhibited insufficient safety profiles to warrant casual use in clinical settings. Hyaluronic acid, on the other hand, appears to demonstrate safety while also mitigating risks associated with concurrent compounds, thereby facilitating therapeutic combinations. Additionally, there remains a paucity of data regarding platelet-rich plasma, necessitating further evaluation of its potential efficacy and safety. Overall, it seems that results are significantly influenced by the dosage and frequency of injections administered, observed in both human and animal studies.

Intra-articular hydrogel formulation prolongs the in vivo stability of Toll-like receptor antagonistic peptides for rheumatoid arthritis treatment.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic inflammation that primarily affects joint tissue and requires frequent medication. Recently, we developed cyclic phage-display-derived inhibitory peptides (CPs), which act as Toll-like Receptor 4 antagonists. These CPs exhibited therapeutic efficacy against joint diseases by alleviating inflammatory factors. Nonetheless, CP exhibits in vivo instability and a short half-life. Therefore, this study sought to improve the in vivo stability of CP, thereby reducing the frequency of CP administration through the development of an injectable hydrogel depot formulation. To improve in vivo stability, CP was chemically conjugated to hyaluronic acid (HA-CP) and subsequently mixed into a temperature-sensitive hydrogel [methoxy polyethylene glycol-b-poly(ε-caprolactone)-ran-poly(lactide) (PC)] as an injectable depot (PC+(HA-CP)). For comparison, CP was physically mixed with HA and PC (PC+(HA+CP)). Both PC+(HA-CP) and PC+(HA+CP) were found to rapidly form depots upon injection into the joint space. Cell viability assays confirmed the non-toxic nature of PC+(HA-CP) and PC+(HA+CP), whereas both formulations exhibited inhibition of inflammatory factors. Furthermore, PC+(HA-CP) retained CP for a longer duration compared to PC+(HA+CP) in the presence of hyaluronidase and within the RA joint space. Following intra-articular injection, both the PC+(HA-CP) and PC+(HA+CP) depots exhibited reductions in RA symptoms, cartilage regeneration, and suppression of pro-inflammatory cytokine levels. Specifically, by extending the in vivo retention of CP, PC+(HA-CP) demonstrated superior RA treatment efficacy compared to PC+(HA+CP). In conclusion, intra-articular injection of PC+(HA-CP) was validated as an effective strategy for treating RA, owing to its ability to prolong the in vivo retention of CP. This approach holds promise for improving RA management and patient outcomes.

Intra-articular administration of extra-virgin olive oil in degenerative osteoarthritis.

BACKGROUND: We aimed to analyze the outcomes of intraarticular extra virgin olive oil (EVOO) injection on mechanically induced rabbit knee osteoarthritis (OA) by studying the morphological, histological, and radiological findings. METHODS: The study was conducted on 32 New Zealand White rabbits. The randomly numbered subjects were divided into two main groups. The rabbits numbered 1 to 16 were selected to be the group to receive EVOO, and the remaining were selected into a control group. Both groups were separated into two subgroups for short-term (five weeks) and long-term (10 weeks) follow-up. Anterior cruciate ligament transection was applied on the left knees of all the rabbits via medial parapatellar arthrotomy to simulate knee instability. Immediately after the surgical procedure, 0.2 cc of EVOO was injected into the knee joint of rabbits numbered 1-16, and the control group received 0.2 cc of sterile saline. On the 14th day, long-term group subjects were administered another dose of 0.2 cc EVOO intraarticularly. RESULTS: The gross morphological scores of the control group subjects were significantly different from the EVOO group for both short-term (p = 0,055) and long-term (p = 0,041) scores. In parallel, the MRI results of the EVOO subjects were significantly different from the control group for both short-term and long-term follow-up assessment scores (p = 0.017, p = 0.014, respectively). The Mankin scoring results showed that there were statistically significant differences between the EVOO and control group in the comparison of both total scores (p = 0.001 for short-term and p = 0.004 for long-term) and subgroup scoring, including macroscopic appearance, chondrocyte cell number, staining, and Tidemark integrity in both short-term (p = 0.005, p = 0.028, p = 0.001, p = 0.005, respectively) and long-term assessments (p = 0.002, p = 0.014, p < 0.001, p = 0. 200, respectively). CONCLUSIONS: We have observed promising outcomes of intra-articular application of extra virgin olive oil in the treatment of acute degenerative osteoarthritis in rabbit knees. Due to its potential cartilage restorative and regenerative effects, EVOO, when administered intra-articularly, may be a promising agent to consider for further research in the treatment of OA.

The necessity of suction drainage when intra-articular injection of tranexamic acid is used during primary total knee arthroplasty: a retrospective study.

BACKGROUND: Suction drainages are commonly used after total knee arthroplasty (TKA) procedures; however, their use is somewhat controversial. Recently, some reports have claimed that the administration of tranexamic acid (TXA) may prevent postoperative bleeding following TKAs. Although numerous studies have reported regarding different dosages, timings of administration, or drain clamping times for intravenous and intra-articular TXA injections (IA-TXAs), few have examined whether suction drainage is necessary when TXA is administered. In this study, we compared using suction drainage without TXA administration and IA-TXA without suction drainage and aimed to examine the need for suction drainage during IA-TXA. METHODS: This retrospective study was conducted on 217 patients who had received TKA for osteoarthritis; 104 were placed on suction drainage after TKA without TXA (Group A), whereas the remaining 113 received IA-TXA immediately after surgery without suction drainage (Group B). Our clinical evaluation included assessments of the need for transfusion, presence of postoperative complications, incidence of deep vein thrombosis (DVT), and changes in hemoglobin (Hb), hematocrit (Hct), and D-dimer levels. RESULTS: No significant differences were observed in terms of postoperative complications and preoperative Hb, Hct, or D-dimer levels between the two groups. Although the prevalence of DVT was significantly higher in Group B (p < 0.05), all cases were asymptomatic. Hb and Hct levels were significantly lower in Group A than in Group B at 1, 3, 7, and 14 days postoperatively (p < 0.05), although none of the cases required blood transfusions. D-dimer levels were significantly higher in Group A than in Group B at 1 and 3 days postoperatively (p < 0.05). CONCLUSION: Suction drainage might not be necessary when IA-TXA is administered after TKA procedures.

The efficacy and safety of intra-articular injection of corticosteroids in multimodal analgesic cocktails in total knee arthroplasty-a historically controlled study.

Background: Total knee arthroplasty (TKA) is a common and effective procedure. Optimizing pain control and reducing postoperative discomfort are essential for patient satisfaction. No studies have examined the safety and efficacy of intra-articular corticosteroid injections following TKA. This study aims to examine the safety and efficacy of corticosteroids in intra-articular multimodal analgesic injections. Materials and methods: This was a historically controlled study conducted at a single academic institution. Before May 2019, patients received an intra-articular cocktail injection without corticosteroids during surgery, referred to as the non-corticosteroid (NC) group. After June 2019, intraoperatively, patients received an intra-articular cocktail injection containing corticosteroids, referred to as the corticosteroid (C) group. Finally, 738 patients were evaluated, 370 in the C cohort and 368 in the NC cohort. The mean follow-up duration was 30.4 months for the C group and 48.4 months for the NC group. Results: The mean VAS scores at rest on postoperative day (POD) 1 (2.35) and POD3 (3.88) were significantly lower in the C group than those in the NC group, which were 2.86 (POD1) and 5.26 (POD3) (p < 0.05). Walking pain in the C group (4.42) was also significantly lower than that (5.96) in the NC group on POD3 (p < 0.05). Patients in the C group had a significantly higher mean range of motion (ROM) (92.55) on POD3 than that (86.38) in the NC group. The mean time to straight leg raise for group C (2.77) was significantly shorter than that (3.61) for the NC group (p < 0.05). The C group also had significantly fewer rescue morphine (1.9) and metoclopramide (0.21) uses per patient than the NC group, which were 3.1 and 0.24, respectively. No significant differences in fever or vomiting rates between groups were found. Patients in neither group developed periprosthetic joint infections or skin necrosis. One patient in the C group suffered from wound dehiscence, and the wound healed well after debridement. No patient died or had a re-operation in either group. Conclusions: This pilot trial found that intra-articular injection of multimodal analgesia (including corticosteroids) reduced initial postoperative pain, increased ROM in the early postoperative days (up to POD3), and did not increase wound complications or infection rates in approximately 30 months of follow-up.

Role of Autologous Micro-Fragmented Adipose Tissue in Osteoarthritis Treatment.

Osteoarthritis (OA) is the most common complex musculoskeletal disorder, resulting from the degeneration of the articular cartilage and characterized by joint pain and dysfunction that culminate in progressive articular cartilage loss. We present our experience in the management of hip and knee OA by means of the intra-articular injection of fat micrograft, describing our approach, which was developed from the belief in the powerful reparative effect of autologous fat graft on damaged tissue, as well as its natural lubricating effect on the joints. Inclusion criteria were as follows: men and women, aged 20 to 80 years, that referred articular pain of the hips and/or knees, showing initial-stage degenerative OA. From October 2018 to July 2023, a total of 250 patients underwent treatment with the Sefficare® device (SEFFILINE srl, Bologna, Italy). The Superficial Enhanced Fluid Fat Injection device was used to perform autologous regenerative treatments in a safe, standardized, easy, and effective way on 160 women, 64%, and 90 men, 36%. A total of 190 procedures (76%) involved the knees, with 20 patients who were bilaterally treated, while 60 procedures, all unilateral, involved the hips (24%). The mean age at treatment was 52.4 years. Before treatment, each patient had undergone X-rays and Magnetic Resonance Imaging (MRI) of the painful hip/knee to evaluate and grade the articular OA. Postoperatively, each patient was assessed after one, three, six, and twelve months. The donor site postoperative course was uneventful other than minimal discomfort. Clinically, the ROM (range of motion) of the treated knee/hip increased an average of 10 degrees 3 months after treatment, but the stiffness was reduced, as reported by the patients. The VAS (Visual Analog Scale) was submitted at 3, 6, and 12 months, demonstrating a progressive reduction of pain, with the best score obtained at six months postoperatively. In total, 85% of patients were satisfied one year after treatment, with a considerable improvement in pain and quality of life. The satisfactory outcome of this minimally invasive procedure indicates that the intra-articular injection of fat micrograft can replace or considerably delay the need for the classical major joint replacement surgery, thanks to its impact on the quality of life of patients and financial cost.

A systematic review of randomized control trials looking at functional improvement of rotator cuff partial thickness tears following platelet-rich-plasma injection: a comparison of glenohumeral joint vs. subacromial bursa vs. intratendinous injection locations.

Background: Prior research has demonstrated that platelet-rich plasma (PRP) has shown promising results in the treatment of knee osteoarthritis, lateral epicondylitis, and rotator cuff disease. However, there is a lack of standardization with PRP regarding its use for partial thickness rotator cuff tears (PTRCTs). The primary objective of this review is to assess the location of PRP injections in the shoulder, and how it corresponds to shoulder functional outcomes in PTRCTs. Methods: Data sources included randomized controlled trials (RCTs) conducted between January 2010 and September 2021 with the terms PRP, partial thickness rotator cuff tears, intra-articular injections, subacromial injections, and intratendinous injections. Major inclusion criteria: partial thickness rotator cuff tears only, functional outcome scores pre-injection and post-injection, minimum 2-month follow-up time, and nonsurgical PRP injections only. Major exclusion criteria: PRP used as an adjunct therapy, full-thickness rotator cuff tears, and surgical intervention before treatment. Results: A total of 8 RCTs were included which utilized PRP injected into the shoulder for PTRCTs. Studies were grouped by the location of the injection with the following breakdown: 1 glenohumeral joint, 4 subacromial bursa, and 3 intratendinous as the site of injection of PRP. Intra-articular PRP showed a 46.2% improvement (P < .05) in the Disabilities of the Arm, Shoulder, and Hand score at 12-month follow-up, however PRP compared to physical therapy had no statistical difference. For subacromial injections, one study showed no statistical difference between hyaluronic acid and PRP vs PRP, but both groups showed improvement compared to normal saline at 3, 6, and 12 months (P < .05). For intratendinous injections, PRP was found to be superior in the Shoulder Pain and Disability Index scores at 66.1% improvement (P < .05) at 3 months and 71.6% at 6 months (P < .05) after two PRP injections when compared to dry needling. Another study showed a statistically significant difference in ASES score when combining LP-PRP injection intratendinous and subacromial bursa when compared to corticosteroid at 3 months. Furthermore, at 6-month follow-up, the PRP group showed significant improvement in the Oxford Shoulder Score compared to a subacromial bursa corticosteroid group 53.8% vs 31.7% (P < .01). Conclusion: Based on our review of current literature, there is inconclusive evidence of the ideal location to inject PRP when partial rotator cuff tear is present. Despite PRP showing improved functional outcomes in patients diagnosed with PTRCT regardless of the injection site, more research is needed to figure out the optimal concentration of PRP, frequency of injection, and who are ideal candidates when utilizing PRP for PTRCTs.

Ultrasound-Guided Hip Injections with High Density Hyaluronic Acid: Outcome at One Year Follow Up.

Background: The ultrasound-guided viscosupplementation of the hip joint with hyaluronic acid (HA) is considered a standard procedure among the conservative treatments for hip arthritis. The aim of this study was to evaluate the clinical benefit and the incidence of adverse events of the technique in an observational study at one year follow up. Methods: We evaluated a consecutive series of 85 patients with a diagnosis of symptomatic arthritis who underwent intra-articular ultrasound-guided hyaluronic acid injections. The scales used for evaluation were modified Harris Hip Score (mHHS), WOMAC (Western Ontario and McMaster University), and Hip Outcome Score (HOS) with subscale Sport (HOSs), for pain the Visual Analogic Scale (VAS). The patients were classified according to Tonnis' radiological classification of arthritis (range 0-3): 20 patients (grade 0), 32 (grade 1), 18 (grade 2), 15 (grade 3). Results: At last follow up, all the scales increased: mHHS from 59.35 to 82.1, HOS from 69.45 to 78.53, HOss from 47.4 to 58.11, VAS from 6.09 to 3.97, WOMAC from 33.2 to 31.5 (p < 0.05 for all the parameters); the results were elaborated with GraphPad Prism v5.0 (Prism Software La Jolla, CA, USA) using Wilcoxon's test. A total of 13 patients out of 85 needed arthroplasty, all classified as Tonnis grade 3. No serious adverse events were noted due to the procedure. Conclusions: Based on our findings, indication for the use of hyaluronic acid is limited to patients with mild to moderate arthritis. Patients in advanced arthritis refusing replacement surgery and asking for this treatment should be informed about the poor results of the technique even in the short term.

Comparison of ultrasound guidance with landmark guidance for symptomatic benefits in knee, hip and hand osteoarthritis: Systematic review and meta-analysis of randomised controlled trials.

Introduction: More than half of the patients with moderate and severe osteoarthritis (OA) report unsatisfactory pain relief, requiring consideration of intra-articular (IA) injections as the second-line management. Ultrasound-guided IA injection has proven evidence of higher accuracy in administering IA injectates into the joints than landmark-guided or blind IA injections. However, questions remain about translating higher accuracy rates of ultrasound-guided injection into better clinical improvements. Therefore, we examined the symptomatic benefits (pain, function and patient satisfaction) of ultrasound-guided injection in knee, hip and hand OA compared with blind injections by synthesising a systematic review and meta-analysis of randomised controlled trials (RCT). Methods: PubMed, Medline and Embase databases were searched for eligible studies from their inception to August 28, 2023. Results: Out of 295 records, our meta-analysis included four RCTs (338 patients with knee OA), demonstrating significant improvement in procedural pain [-0.89 (95% CI -1.25, -0.53)], pain at follow-up [-0.51 (95% CI -0.98, -0.04)] and function [1.30 (95% CI 0.86, 1.73)], favouring ultrasound guidance. One single study showed higher patient satisfaction with ultrasound guidance. Conclusion: Ultrasound-guided IA injection provided superior clinical outcomes compared with landmark-guided IA injection.

Extended-Release Versus Immediate-Release Triamcinolone Acetonide in Patients Who Have Knee Osteoarthritis and Type 2 Diabetes Mellitus.

BACKGROUND: Intra-articular (IA) corticosteroid injections may cause hyperglycemia (glucose level > 180 mg/dL). In a phase 2 study of 33 patients who had osteoarthritis of the knee (OAK) and type 2 diabetes mellitus (T2D), triamcinolone acetonide extended-release (TA-ER) was associated with minimal glycemic control disruption compared with triamcinolone acetonide immediate-release (TA-IR). This post hoc analysis characterizes the clinical relevance of these results. METHODS: Patients who had symptomatic OAK for ≥ 6 months, T2D for ≥ 1 year, and hemoglobin A1c ≥ 6.5 and ≤ 9.0% were randomized to receive an IA injection of either TA-ER or TA-IR. Changes in continuous glucose monitor daily glucose level, percentage of time in or above the target glucose range (> 70 to 180 mg/dL), time to glucose level 250 mg/dL and maximum glucose level > 250 mg/dL, and glycemic variability were evaluated. RESULTS: Across postinjection days 1 to 3, the TA-ER group (n = 18) had a lower median change from baseline in maximum glucose level (92.3 versus 169.1 mg/dL), a reduced percentage of time with a glucose level > 250 mg/dL (12 versus 26%), a smaller proportion of patients who had a maximum glucose level > 250 mg/dL (50 versus 93%), and a greater percentage of time in the target glucose range (62 versus 48%) versus the TA-IR group (n = 15). There was less glycemic variability and lower glucose spikes in the TA-ER versus TA-IR group. Median times to glucose level 250 mg/dL (44 versus 6 hours) and maximum glucose level (34 versus 13 hours) were significantly longer in the TA-ER versus TA-IR group. CONCLUSIONS: Use of TA-ER was associated with a clinically meaningful reduction in hyperglycemia versus TA-IR.

BRD2-specific inhibitor, BBC0403, inhibits the progression of osteoarthritis pathogenesis in osteoarthritis-induced C57BL/6 male mice.

BACKGROUND AND PURPOSE: The discovery of new bromo- and extra-terminal inhibitors presents new drugs to treat osteoarthritis (OA). EXPERIMENTAL APPROACH: The new drug, BBC0403, was identified in the DNA-encoded library screening system by searching for compounds that target BRD (bromodomain-containing) proteins. The binding force with BRD proteins was evaluated using time-resolved fluorescence energy transfer (TR-FRET) and binding kinetics assays. Subsequently, in vitro and ex vivo analyses demonstrated the effects of the BRD2 inhibitor, BBC0403, on OA. For animal experiments, medial meniscus destabilization was performed to create a 12-week-old male C57BL/6 mouse model, and intra-articular (i.a.) injections were administered. Histological and immunohistochemical analyses were then performed. The underlying mechanism was confirmed by gene set enrichment analysis (GSEA) using RNA-seq. KEY RESULTS: TR-FRET and binding kinetics assays revealed that BBC0403 exhibited higher binding specificity for BRD2 compared to BRD3 and BRD4. The anti-OA effects of BBC0403 were tested at concentrations of 5, 10 and 20 µM (no cell toxicity in the range tested). The expression of catabolic factors, prostaglandin E2 (PGE2) production and extracellular matrix (ECM) degradation was reduced. Additionally, the i.a. injection of BBC0403 prevented OA cartilage degradation in mice. Finally, BBC0403 was demonstrated to suppress NF-κB and MAPK signalling pathways. CONCLUSION AND IMPLICATIONS: This study demonstrated that BBC0403 is a novel BRD2-specific inhibitor and a potential i.a.-injectable therapeutic agent to treat OA.

Intra-articular injection of miRNA-1 agomir, a novel chemically modified miRNA agonists alleviates osteoarthritis (OA) progression by downregulating Indian hedgehog in rats.

Our objective in this study is to determine whether intra-articular injection of miRNA-1 can attenuate the progression of OA in rats by down regulating Ihh. Knee chondrocytes were isolated from male Sprague-Dawley rats aged 2-3 days. Second-generation chondrocytes were transfected with miR-1 mimic and empty vector with lipo3000 for 6 h and then stimulated with 10 ng/mL IL-1ß for 24 h. OA-related and cartilage matrix genes were quantified using real-time quantitative polymerase chain reaction (RT-qPCR). Two-month-old male Sprague-Dawley rats were divided into three groups (n = 30?): sham operation group + 50 µL saline, anterior cruciate ligament transection (ACLT) group + 50 µL miR-1 agomir (concentration), and control group ACLT + 50 µL miR-1 agomir. Treatment was started one week after the operation. All animals were euthanized eight weeks after the operation. X-rays and micro-CT were used to detect imaging changes in the knee joints. FMT was used to monitor joint inflammation in vivo. Safranin O staining was used to detect morphological changes in articular cartilage. Immunohistochemistry was used to detect Col2, Col10, metalloproteinase-13 (MMP-13). RT-qPCR was used to detect gene changes includingmiR-1, Col2, Col10, MMP-13, Ihh, Smo, Gli1, Gli2, and Gli3. Overexpression of miR-1 in IL-1ß-stimulated chondrocytes reduced the levels of Ihh, MMP-13, and Col10 but increased the levels of Col2 and aggrecan. Intra-articular injection of miR-1 agomir reduced osteophyte formation, inflammation, and prevented cartilage damage. RT-qPCR results indicated that the miR-1 agomir increased articular cartilage anabolism and inhibited cartilage catabonism. miR-1 can attenuate the progression of OA by downregulating Ihh.

Oxygen-ozone therapy for pain relief in patients with trapeziometacarpal osteoarthritis: a proof-of-concept study.

PURPOSE: Trapeziometacarpal osteoarthritis (TMC-OA) is a prevalent hand disorder affecting a growing number of people worldwide. While a multidisciplinary approach might provide additional advantages, the analgesic and anti-inflammatory role of intra-articular oxygen-ozone (O2O3) injections combined with physical therapy is still unknown. To assess the impact of a multimodal therapeutic approach combining O2O3 injections with physical therapy in patients with TMC-OA. MATERIALS AND METHODS: A prospective open-label study conducted in the Physical and Rehabilitation Medicine Unit of the "Renato Dulbecco" University Hospital of Catanzaro. We assessed patients with TMC-OA who had not responded to standard medical therapy. Participants received O2O3 therapy and targeted physical therapy for 4 weeks. Pain relief, muscle strength, and physical functioning were assessed at baseline and after 4, 12 and 24 weeks (respectively T0, T1, T2, and T3). RESULTS: Seventeen patients with a mean age of 67.1 ± 6.1 years were included in the study. Short-term improvements in pain intensity were observed (T0: 6.221 ± 1.514; T1: 3.172 ± 1.1451; p < .001) and were maintained over a 24-week follow-up period (T0: 6.221 ± 1.514; T3: 4.393 ± 1.438; p: 0.006). Significant changes were reported also in terms of muscle strength and physical functioning. O2O3 therapy was well-tolerated with no adverse effects. CONCLUSIONS: A combination of O2O3 injections and physical therapy might be considered in patients with TMC-OA. Further investigation is warranted to assess the effectiveness of O2O3 therapy in managing TMC-OA.

The addition of intra-articular trapeziometacarpal O₂O₃ injections to physical therapy is safe and reliable for thumb osteoarthritisO₂O₃ injection could be considered a second-line mini-invasive approach option when simple analgesic and non-pharmacologic interventions have failed, and surgical treatment is not yet indicatedO₂O₃ injections in combination with physical therapy may provide benefits in terms of pain relief in patients with TMC joint OA in whom previous conventional medical therapy has been unsuccessful.