UNASSIGNED: Intra-articular corticosteroid injections (IACS) are interventions which provide pain relief in knee osteoarthritis (OA). It remains unclear whether IACS have a deleterious effect on knee cartilage structure.
UNASSIGNED: To estimate the effect of IACS on cartilage structure in patients with knee OA, using joint space width (JSW) (in radiographic studies), and cartilage thickness (in magnetic resonance imaging).
UNASSIGNED: A literature search was performed to identify randomized control trials and observational studies published from inception to June 15, 2022. Studies were included if patients received IACS for knee OA, with a control arm. Given the different metrics used in reporting continuous variable outcomes among studies, pooled estimates for cartilage thickness change were assessed using standardized mean differences (defined as the difference between the means of the groups divided by a within-group standard deviation) to odds ratio transformation. Sensitivity analyses were conducted based on outcome metric, imaging modality, and number of injections.
UNASSIGNED: Six studies (1437 participants) were identified. The estimated effect of IACS on cartilage structure revealed greater odds of cartilage structure worsening (Odds Ratio (OR): 2.01, 95% Confidence Interval (CI): 1.18,3.44). Sensitivity analyses revealed similar trends, with significant results for singular injections with preference to JSW (OR: 2.44, 95%CI: 1.23,4.82), radiographic outcomes with preference to KL grade (OR: 2.03, 95%CI: 1.01,4.10), binary outcomes with preference to KL grade (OR: 2.93, 95%CI: 1.18,7.25) and quantitative measures (Standardized Mean Differences (SMD): -0.34, 95%CI: -0.66, -0.02).
UNASSIGNED: IACS use may contribute to imaging features of knee cartilage loss. Further studies are warranted to investigate the underlying pathogenesis.

OBJECTIVE: To quantify the clinical relevance of intra-articular corticosteroid effects compared to placebo for the injective treatment of knee osteoarthritis (OA).
METHODS: The PubMed, Cochrane Library and Web of Science databases were searched on May 3, 2023. This study was conducted in accordance with the PRISMA guidelines. The inclusion criteria were randomized controlled trials (RCTs), published in English, with no time limitation regarding publication date, comparing intra-articular corticosteroids and placebo injections for knee OA. The effects were quantified at short- (≤6 weeks), mid- (>6 weeks and ≤3 months), and long-term (≥6 months) follow-ups. The minimal clinically important difference (MCID) for the outcomes (visual analogue scale for pain - VAS: 1.4, Western Ontario and McMaster University Osteoarthritis Index - WOMAC: 9) was used to interpret the clinical improvement provided by intra-articular corticosteroid injections compared to placebo. The quality of each article was assessed using the Cochrane RoB 2 tool and the GRADE guidelines.
RESULTS: Among the 1030 articles retrieved, 11 RCTs (842 patients) were included. A comparison of the two groups revealed statistically significant differences in the improvement of VAS and WOMAC scores in terms of the mean difference (MD); this difference was in favour of corticosteroids at short-term (p < 0.001, MD = -1.6 and p < 0.001, MD = -9.9, respectively) and mid-term follow-ups (p = 0.001, mean MD = -1.3 and p = 0.005, MD = -4.9, respectively). No difference was observed at the long-term follow-up. The MDs between the improvements in the two groups reached the MCID values for the VAS and WOMAC only at the short-term follow-up. The RoB 2 tool and the GRADE evaluations showed the presence of risk of bias and limited quality of evidence.
CONCLUSIONS: This systematic review and meta-analysis demonstrated that intra-articular corticosteroid injections offer clinically perceivable pain relief and functional improvement higher than the placebo effect only at short-term follow-up in patients affected by knee OA, with benefits losing clinical relevance already after 6 weeks. These results, together with the low number and the limited quality of the RCTs comparing this treatment with placebo, question the indication for the use of corticosteroid injections in clinical practice for the treatment of knee OA.
METHODS: Level I.

Background  Treatment of intra-articular distal radius fractures (DRFs) rests on anatomic internal fixation. Fragment-specific fixation (FSF) is applied when fracture pattern is too complex for standard volar plating (SVP), oftentimes with potential increased risk of complications. We hypothesized that patients undergoing FSF would achieve less wrist range of motion (ROM) with higher risk of complications compared with SVP. Methods  We conducted a retrospective review of 159 consecutive patients undergoing DRF fixation from 2017 to 2020. Patients < 18 years old, < 8 weeks\' follow-up, open fractures, ipsilateral trauma, and fractures requiring dorsal spanning plate were excluded. Patient demographics, specific construct type, AO fracture classification, ROM, and complications were assessed. ROM was calculated using average flexion, extension, supination, and pronation. t -Tests were used to determine differences in ROM among construct types. Results  Ninety-two patients met all inclusion criteria: 59 underwent SVP and 33 underwent FSF. Average wrist ROM for patients undergoing SVP was 57 degrees/50 degrees flexion-extension and 87 degrees/88 degrees supination-pronation; average ROM for patients undergoing FSF was 55 degrees/49 degrees flexion-extension and 88 degrees/89 degrees supination-pronation. No significant differences were identified when comparing final wrist flexion ( p  = 0.08), extension ( p  = 0.33), supination ( p  = 0.35), or pronation ( p  = 0.21). Overall reoperation rate was 5% and higher for FSF (12%) versus SVP (2%). Highest reoperation rate was observed in the double volar hook cohort (80%; N  = 4). Conclusion  Construct type does not appear to affect final ROM if stable internal fixation is achieved. SVP and FSF had similar complication rates; however, double volar hook constructs resulted in increased reoperations likely from fixation failure and plate prominence. Level of Evidence  Level IV, retrospective review.

OBJECTIVE: To assess the efficacy of intra-articular viscosupplementation as a therapeutic intervention for hip osteoarthritis (OA), as well as to assess the duration of efficacy, effect of dose, composition and number of injections of the viscosupplement, and the incidence of adverse effects.
METHODS: We performed a systematic review using the literature search from the following databases: Embase, Medline, PubMed, Web of Science, and Scopus. Quality assessment of the included studies was performed using the Modified Newcastle-Ottawa Quality Assessment Scale. Random-effects meta-analysis and mixed-effects subgroup analysis were carried out, but due to the high heterogeneity, low level of evidence, and high risk of bias of the included studies after analyzing the data, weighted means and pooled estimates have not been provided. Instead, we have provided a subjective synthesis of the results.
RESULTS: Forty studies were included in the analysis from an initial search of 3,265 studies, with data from a total of 3,350 patients. The level of available evidence was low with an overall high risk of bias. Nearly all studies showed a reduction in mean pain at 1 month, 3 months, and 6 months of follow-up, as well as at the end point, and an improvement in mean patient-reported function was also seen at these time points. However, heterogeneity was extremely high at all time points and remained despite attempts at removing outliers. Subgroup analyses looking at the effects of dose, volume, composition of viscosupplement, and number of injections were carried out, but substantial heterogeneity still remained. There were no lasting adverse effects.
CONCLUSIONS: Weak evidence suggests that viscosupplementation improves patient-reported pain and function at end point compared to baseline, regardless of dose, volume, composition, and number of injections. However, due to the high heterogeneity, low level of evidence, and high risk of bias in the current available literature, the strength of our conclusions is limited.
METHODS: Level IV, systematic review of level I to IV studies.

Equine practitioners frequently inject local anaesthetics (LA) intra-articularly in both diagnosis of lameness and for pain management intra- or post-operatively with synovial endoscopy. Recent reviews of the human and veterinary literature support the concept that chondrotoxicity of LA on joint tissues depends on the type of drug, dose administered, and duration of exposure. The purpose of this review is to summarise the current literature describing intra-articular local anaesthetic use, including both in vitro and in vivo studies, and to draw some comparisons to literature from other species where potential toxicity and duration of effect have been evaluated with the goal of advancing the field\'s understanding of intra-articular local anaesthetic use in horses, and indicating future directions for the field. The aggregate data available from all species, while generally sparse for horses, indicate that LA are rapidly cleared from the synovial fluid after injection, often within 30 min. In vitro data strongly suggest that lidocaine and bupivacaine are likely more chondrotoxic than other LA, although to what extent is still unknown, and cytotoxicity of LA may be mitigated through concurrent injection with HA, PRP, and drug combinations including nonsteroidal anti-inflammatories and opioids. The current body of in vitro research is not reflective of the in vivo environment, and further in vitro work, if performed, should focus on mimicking the native joint environment, utilising PK data and joint/injection volumes to replicate the native environment more accurately within the joint and the expected exposures to LA.

Hemophilia is an inherited X-linked bleeding condition with predominant joint involvement due to intra-articular bleeding, hemosiderin deposition and the synovial hypertrophy that is responsible for cartilage destruction, joint deformity and malalignment, pain and functional restriction. Management of chronic arthropathy includes conservative and surgical approaches. Conservative therapies consist of pain modulation, oral drugs, physiotherapy and intra-articular agents. For the present review, the literature was searched for intra-articular agents and 20 papers on the use of corticosteroids (CS), hyaluronic acid (HA) and platelet-rich plasma (PRP), with different regimes of administration, were included. CS had a longer record of injection, with statistically significant pain reduction and functional improvement in the short-term and moderate persistence in the long-term. HA was able to improve the clinical and functional status of joints with moderate or severe hemophilia. PRP was relatively recently introduced to joint management and the results remain controversial. Different associations between the above-mentioned agents were proposed by studies including a small number of patients, producing comparable results. It was concluded that there is a need for extensive research on intra-articular agents, with stratification according to the severity of joint involvement. The lack of a blinded or placebo-controlled arm due to ethical aspects makes the task challenging.

OBJECTIVE: Aim of this systematic review was to determine if bone marrow-derived cell-based injectable therapies induce disease-modifying effects in joints affected by osteoarthritis (OA) in animal models.
METHODS: A systematic review was performed on three electronic databases (PubMed, Web of Science, Embase) according to PRISMA guidelines. A synthesis of the results was performed investigating disease-modifying effects in preclinical animal studies comparing injectable bone marrow-derived products with OA controls or other products, different formulations or injection intervals, and the combination with other products. The risk of bias was assessed according to the SYRCLE\'s tool.
RESULTS: Fifty-three studies were included (1819 animals) with an increasing publication trend over time. Expanded cells were used in 48 studies, point-of-care products in 3 studies, and both approaches were investigated in 2 studies. Among the 47 studies presenting results on the disease-modifying effects, 40 studies (85%) reported better results with bone marrow-derived products compared to OA controls, with positive findings evident in 14 out of 20 studies (70%) in macroscopic assessment, in 30 out of 41 studies (73%) in histological assessment, and in 10 out of 13 studies (77%) in immunohistochemical evaluations. Clinical evaluations showed positive results in 7 studies out of 9 (78%), positive imaging results in 11 studies out of 17 (65%), and positive biomarker results in 5 studies out of 10 (50%). While 36 out of 46 studies (78%) reported positive results at the cartilage level, only 3 out of 10 studies (30%) could detect positive changes at the synovial level. The risk of bias was low in 42% of items, unclear in 50%, and high in 8%.
CONCLUSIONS: This systematic review of preclinical studies demonstrated that intra-articular injections of bone marrow-derived products can induce disease-modifying effects in the treatment of OA, slowing down the progression of cartilage damage with benefits at macroscopic, histological, and immunohistochemical levels. Positive results have been also observed in terms of clinical and imaging findings, as well as in the modulation of inflammatory and cartilage biomarkers, while poor effects have been described on the synovial membrane. These findings are important to understand the potential of bone marrow-derived products and to guide further research to optimise their use in the clinical practice.
METHODS: II.

The purpose of the present paper was to review the available evidence on intra-articular botulinum toxin (BTX) injection in the treatment of knee osteoarthritis and to compare it to other conservative treatment options. A systematic review of the literature was performed on the PubMed, Scopus, Cochrane Library, Web of Science, Pedro and Research Gate databases with the following inclusion criteria: (1) randomized controlled trials (RCTs), (2) written in the English language, and (3) published on indexed journals in the last 20 years (2001-2021) dealing with the use of BTX intra-articular injection for the treatment of knee OA. The risk of bias was assessed using the Cochrane Risk of Bias tool for RCTs. Nine studies involving 811 patients in total were included. Patients in the control groups received different treatments: conventional physiotherapy, hyaluronic acid injection or prolotherapy or a combination thereof in 5 studies, steroid infiltrative therapy (triamcinolone) in 1 study, placebo in 2, and local anesthetic treatment in 1 study. Looking at the quality of the available literature, two of the included studies reached \"Good quality\" standard, three were ranked as \"Fair\", and the rest were considered \"Poor\". No major complications or serious adverse events were reported following intra-articular BTX, which provided encouraging pain relief, improved motor function, and quality of life. Based on the available data, no clear indication emerged from the comparison of BTX with other established treatments for knee OA. The analysis of the available RCTs on BTX intra-articular injection for the treatment of knee OA revealed modest methodological quality. However, based on the data retrieved, botulinum toxin has been proven to provide good short-term outcomes, especially in patients with pain sensitization, by modulating neurotransmitter release, peripheral nociceptive transduction, and acting on the control of chronic pain from central sensitization.

OBJECTIVE: The aim of this systematic review was to determine if adipose tissue-derived cell-based injectable therapies can induce disease-modifying effects in joints affected by osteoarthritis (OA).
METHODS: A systematic review was performed on three electronic databases (PubMed, Web of Science, Embase) according to PRISMA guidelines. A synthesis of the results was performed investigating disease-modifying effects in preclinical studies comparing injectable adipose-derived products with OA controls or other products, different formulations or injection intervals, and the combination with other products. The risk of bias was assessed according to the SYRCLE\'s tool.
RESULTS: Seventy-one studies were included (2,086 animals) with an increasing publication trend over time. Expanded cells were used in 65 studies, 3 studies applied point of care products, and 3 studies investigated both approaches. Overall, 48 out of 51 studies (94%) reported better results with adipose-derived products compared to OA controls, with positive findings in 17 out of 20 studies (85%) in macroscopic, in 37 out of 40 studies (93%) in histological, and in 22 out of 23 studies (96%)  in immunohistochemical evaluations. Clinical and biomarker evaluations showed positive results in 14 studies out of 18 (78%) and 12 studies out of 14 (86%), while only 9 studies out of 17 (53%) of the imaging evaluations were able to detect differences versus controls. The risk of bias was low in 38% of items, unclear in 51%, and high in (11%).
CONCLUSIONS: The current preclinical models document consistent evidence of disease-modifying effects of adipose-derived cell-based therapies for the treatment of OA. The high heterogeneity of the published studies highlights the need for further targeted research to provide recommendations on the optimal methodologies for a more effective application of these injective therapies for the treatment of OA in clinical practice.
METHODS: II.

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.
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.
A systematic review and meta-analysis; Level of evidence, 4.
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.
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.
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.