The effect of sodium hyaluronate on dry eye and corneal epithelial thickness following cataract surgery.

PURPOSE: To evaluate the effects of sodium hyaluronate drops on dry eye parameters and corneal epithelial thickness following cataract surgery. METHODS: The study included 84 patients who underwent uncomplicated phacoemulsification. In Group A, 0.15% sodium hyaluronate drops were added to the postoperative antibiotic/anti-inflammatory treatment. In Group B, only antibiotic/anti-inflammatory treatment was applied. Preoperatively and at 1 week and 1 month postoperatively, all the patients were evaluated in respect of tear break-up time (TBUT), the Schirmer test under anesthesia, the corneal fluorescein staining (CFS) score, mean central corneal thickness (CCT) and mean central corneal epithelial thickness (CCET), and the two groups were compared. RESULTS: A statistically significant difference was determined between the two groups at postoperative 1 month in respect of TBUT, Schirmer test, CFS score, and CCET (p < 0.01). In Group A, a statistically significant increase was determined in the TBUT and Schirmer values at 1 month postoperatively (p < 0.01, p = 0.01, respectively) and in Group B, these values were decreased compared to preoperatively (p < 0.01). The CCET was determined to be significantly thinner in Group B 1 month postoperatively (p < 0.01). A significant increase in CCT was observed in both groups at postoperative 1 week (p < 0.01) and preoperative values were reached at 1 month postoperatively. CONCLUSION: In the patient group using sodium hyaluronate, significant differences were determined in all dry eye parameters and CCET. The use of hyaluronate sodium drops after cataract surgery was seen to improve dry eye parameters and contribute to a healthy ocular surface by ensuring continuity of the corneal epithelium.

A Low Transition Temperature Mixture-based viscosupplementation complemented with celecoxib for osteoarthritis treatment.

Viscosupplementation consists of hyaluronic acid (HA) intra-articular injections, commonly applied for osteoarthritis treatment while non-steroidal anti-inflammatory drugs (NSAIDs) are widely administered for pain relief. Here, HA and a NSAID (celecoxib) were combined in a formulation based on a low transition temperature mixture (LTTM) of glycerol:sorbitol, reported to increase celecoxib's solubility, thus rendering a potential alternative viscosupplement envisioning enhanced therapeutic efficiency. The inclusion of glucosamine, a cartilage precursor, was also studied. The developed formulations were assessed in terms of rheological properties, crucial for viscosupplementation: the parameters of crossover frequency, storage (G') and loss (G'') moduli, zero-shear-rate viscosity, stable viscosity across temperatures, and shear thinning behaviour, support viscoelastic properties suitable for viscosupplementation. Additionally, the gels biocompatibility was confirmed in chondrogenic cells (ATDC5). Regarding drug release studies, high and low clearance scenarios demonstrated an increased celecoxib (CEX) release from the gel (6 to 73-fold), compared to dissolution in PBS. The low clearance setup presented the highest and most sustained CEX release, highlighting the importance of the gel structure in CEX delivery. NMR stability studies over time demonstrated the LTTM+HA+CEX (GHA+CEX) gel as viable candidate for further in vivo evaluation. In sum, the features of GHA+CEX support its potential use as alternative viscosupplement.

Tear film stability in patients with symptoms of dry eye after instillation of dual polymer hydroxypropyl guar/sodium hyaluronate vs single polymer sodium hyaluronate.

PURPOSE: This study evaluated the tear film stability in patients with symptoms of dry eye after installation of dual polymer hydroxypropyl guar/sodium hyaluronate (DPHG/SH) vs single polymer SH. METHODS: Patients with recently diagnosed mild to moderate dry eye disease (OSDI score 23-32 points) were included. For each patient, the right eye was randomized to receive DPHG/SH or 0.15% SH. Just after the administration of the drop to the right eye, the fellow eye received the other eye drop. The first non-invasive Keratograph first break-up time (NIKBUT), average NIKBUT and tear meniscus height (TMH) were measured before administration of the eye drops, at 1-min, 15 min, 30 min, 60 min, 90 min, and 120 min after instillation. RESULTS: A total of 29 patients aged 22.8 ± 2.2 years participated in the study (21 women). No differences between the eye receiving DPHG/SH and single polymer SH were observed for the first NIKBUT (p = 0.45) and average NIKBUT (p = 0.24) variables at any time point. Both DPHG/SH and single polymer SH increased the TMH (p of time effect < 0.001), but with no difference between groups (p = 0.95). CONCLUSION: Both DPHG/SH and single polymer SH solutions provide lubrication of the eye surface, however, with no difference in NIKBUT and TMH evaluations for up to two hours following administration.

Platelet-Rich Plasma, Bone Marrow Aspirate Concentrate, and Hyaluronic Acid Injections Outperform Corticosteroids in Pain and Function Scores at a Minimum of 6 Months as Intra-Articular Injections for Knee Osteoarthritis: A Systematic Review and Network Meta-analysis.

PURPOSE: To compare the efficacy of common intra-articular injections used in the treatment of knee osteoarthritis, including corticosteroid (CS), hyaluronic acid (HA), platelet-rich plasma (PRP), and bone marrow aspirate concentrate (BMAC), with a minimum follow-up of 6-months. METHODS: A literature search was conducted using the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in August 2022 in the following databases: PubMed/MEDLINE, Scopus, Cochrane Database of Controlled Trials, and the Cochrane Database of Systematic Reviews. Level I to II randomized clinical trials with a minimum follow-up of 6 months that investigated the treatments of interest were included. Patient-reported outcome scores for pain and function at baseline and at latest follow-up were extracted, and the change in scores was converted to uniform 0 to 100 scales. Arm-based Bayesian network meta-analysis using a random-effects model was created to compare the treatment arms in pain and function. RESULTS: Forty-eight studies comprising a total of 9,338 knees were included. The most studied intra-articular injection was HA (40.9%), followed by placebo (26.2%), PRP (21.5%), CS (8.8%), and then BMAC (2.5%). HA and PRP both led to a significant improvement in pain compared with placebo. HA, PRP, and BMAC all led to a significant improvement in function scores when compared with placebo. Surface under the cumulative ranking curves (SUCRAs) of the interventions revealed that PRP, BMAC, and HA were the treatments with the highest likelihood of improvement in both pain and function, with overall SUCRA scores of 91.54, 76.46, and 53.12, respectively. The overall SUCRA scores for CS and placebo were 15.18 and 13.70, respectively. CONCLUSIONS: At a minimum 6-month follow-up, PRP demonstrated significantly improved pain and function for patients with knee osteoarthritis compared with placebo. Additionally, PRP exhibited the highest SUCRA values for these outcomes when compared with BMAC, HA, and CS. LEVEL OF EVIDENCE: Level II, meta-analysis of Level I to II studies.

Gait kinematics of osteoarthritic knees after intra-articular viscosupplementation: A double-blinded randomized controlled trial.

BACKGROUND: The utilization of subjective questionnaires for assessing conservative treatment in knee osteoarthritis may present challenges in identifying differences due to inadequate statistical power. Objective tools, such as three-dimensional (3D) kinematic analysis, are accurate and reproducible methods. However, no high-quality studies assessing the effects of intra-articular viscosupplementation (VS) have been published. Therefore, the objective of the study was to evaluate gait kinematics of patients with advanced knee osteoarthritis after VS. METHODS: Forty-two patients were randomized to receive either VS or saline injection (placebo). They underwent 3D kinematic gait analysis before and at 1, 6, and 12 weeks after treatment and knee angles during stance phase were determined. Patients and the healthcare team responsible for data collection, processing, and analysis were blinded to group allocation. Between-group comparisons were conducted using linear mixed models. RESULTS: Compared with placebo, the VS increased the maximum knee extension (3.2° (0.7-5.7)) and decreased the maximum knee flexion (-3.6° (-6.1 to -1.2)) on the sagittal plane at 1 week. At 6 weeks, the VS group sustained a reduced maximum knee flexion (-2.6° (-5.2 to 0.0)). On the axial plane, the VS group demonstrated an increase in maximum internal rotation at 12 weeks (3.9° (0.3 to 7.7)). The VS group exhibited reduced single-leg stance time at 1 week and increased total stance time at 12 weeks. CONCLUSIONS: VS led to short- and long-term kinematic improvements in the sagittal and axial planes, leading to a gait pattern closer to that observed in individuals with less severe osteoarthritic knees.

Different doses of hyaluronic acid injections in patients with knee osteoarthritis: A multicenter, randomized, prospective, single-blind, clinical study.

BACKGROUND: Many formulations and dosing regimens are available for hyaluronic acid (HA). OBJECTIVE: To compare different doses of linear, high-molecular weight (HMW) HA injections among patients with knee osteoarthritis (OA). METHODS: Hundred patients were included in this randomized, single-blinded trial and randomly divided into three HA injection groups. The first group received five weekly 20 mg HA injections, the second group received three weekly 32 mg HA injections, and the third group received a single 48 mg HA injection. Patients were evaluated at baseline, 1, 3, and 6 months after the last injection for pain, stiffness, and function using the visual analog scale (VAS) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire. Quality of life, patient's global assessment, and Timed Up and Go (TUG) test scores were also evaluated. RESULTS: There was significant improvement in the WOMAC, VAS-pain, quality of life, patient's global assessment, and TUG test mean scores at all follow-up time points (p< 0.001). However, the groups showed no significant differences in WOMAC, VAS-activity pain, and patient global scores at any follow-up point. CONCLUSION: Intra-articular injections of different doses of linear HMW HA can improve pain, stiffness, function, and quality of life in patients suffering from knee OA over a six-month period.

Efficacy of a dietary supplement in dogs with osteoarthritis: A randomized placebo-controlled, double-blind clinical trial.

This study is a randomized, placebo-controlled, double-blinded trial performed to investigate the effects of a dietary supplement containing a mixture of Boswellia serrata Roxb., chlorophyll, green tea extract, glucosamine, chondroitin sulfate, hyaluronic acid, and further in the manuscript: non-hydrolised type II collagen in dogs with osteoarthritis (OA). A total of 40 dogs were enrolled in the study, they were randomly divided in control (CTR) and treatment (TRT) groups. The TRT group received the dietary supplement for 60 days. The CTR group received a placebo for the same number of days. All the subjects had veterinary evaluations during the trial and owners were requested to fill in questionnaires on chronic pain using the Helsinki Chronic Pain Index. The product was easy to administer and no side effects were reported. Combining results from veterinarian and owner evaluations, the tested product proved to be significantly beneficial in alleviating pain and in reducing the clinical signs in dogs with OA.

Non-clinical assessment of lubrication and free radical scavenging of an innovative non-animal carboxymethyl chitosan biomaterial for viscosupplementation: An in-vitro and ex-vivo study.

OBJECTIVE: Lubrication and free radical scavenging are key features of biomaterials used for viscosupplementation (VS) of joints affected by osteoarthritis (OA). The objective of this study was to describe the non-clinical performance characterization of KiOmedine® CM-Chitosan, a non-animal carboxymethyl chitosan, in order to assess its intended action in VS and to compare it to existing viscosupplements based on crosslinked hyaluronan (HA) formulations. METHOD: The lubrication capacity of the tested viscosupplements (VS) was evaluated in-vitro and ex-vivo. In-vitro, the coefficient of friction (COF) was measured using a novel tribological system. Meanwhile, an ex-vivo biomechanical model in ovine hindlimbs was developed to assess the recovery of join mobility after an intra-articular (IA) injection. Free radical scavenging capacity of HA and KiOmedine® CM-Chitosan formulations was evaluated using the Trolox Equivalent Antioxidant Capacity (TEAC) assay. RESULTS: In the in-vitro tribological model, KiOmedine® CM-Chitosan showed high lubrication capacity with a significant COF reduction than crosslinked HA formulations. In the ex-vivo model, the lubrication effect of KiOmedine® CM-Chitosan following an IA injection in the injured knee was proven again by a COF reduction. The recovery of joint motion was optimal with an IA injection of 3 ml of KiOmedine® CM-Chitosan, which was significantly better than the crosslinked HA formulation at the same volume. In the in-vitro TEAC assay, KiOmedine® CM-Chitosan showed a significantly higher free radical scavenging capacity than HA formulations. CONCLUSION: Overall, the results provide a first insight into the mechanism of action in terms of lubrication and free radical scavenging for the use of KiOmedine® CM-Chitosan as a VS treatment of OA. KiOmedine® CM-Chitosan demonstrated a higher capacity to scavenge free radicals, and it showed a higher recovery of mobility after a knee lesion than crosslinked HA formulations. This difference could be explained by the difference in chemical structure between KiOmedine® CM-Chitosan and HA and their formulations.

Novel Technique for Descemetorhexis Under Ophthalmic Viscosurgical Devices and Air.

PURPOSE: The aim of this study was to describe a novel technique for descemetorhexis that combines the advantages of stable anterior chamber (AC) associated with ophthalmic viscosurgical devices and optimal surgical visualization seen with air to overcome the issues of poor Descemet membrane (DM) visibility or AC instability when each is used alone. METHODS: This study is a description of a new surgical approach. RESULTS: We describe a new technique for performing descemetorhexis. The simultaneous presence of cohesive ophthalmic viscosurgical device and air in the AC offers optimal DM visualization and guarantees a stable AC during this surgical step. It does not require an additional incision for an AC maintainer. CONCLUSIONS: The described technique may facilitate the surgical step of descemetorhexis, offering improved AC stability and better visualization of the DM. It may reduce early postoperative graft detachment due to the presence of residues of the recipient's diseased DM.

Histopathological features of iatrogenic occlusive vasculopathy caused by intra-articular hyaluronic acid injection for osteoarthritis.

Occlusive vasculopathy may rarely occur after intra-articular injection with hyaluronic acid. The associated histological changes are not well described. Herein, we would like to present representative histology of this phenomenon.

Clinical Outcomes Of Intra-Articular High Molecular Weight Hyaluronic Acid Injection For Hip Osteoarthritis- A Systematic Review And Meta-Analysis.

BACKGROUND: Osteoarthritis is the most common degenerative disease of the synovial joints in the elderly population with hip osteoarthritis as the second most commonly affected joint. A multitude of conservative treatments is used for pain relief and functional improvement including acetaminophen, NSAID, intra-articular corticosteroid, and viscosupplementation (VS). Different preparations of VS based on different molecular weights are commercially available. No systematic review or meta-analysis regarding the use of intra-articular high molecular weight hyaluronic acid (HMWHA) injection for the hip joint was published before. This review analyzes the efficacy of intra-articular HMWHA for hip osteoarthritis. METHODS: PubMed, Google Scholar, Cochrane Library for randomized trials describing the efficacy of HMWHA for hip osteoarthritis was searched. The search terms were osteoarthritis, hip joint, outcomes, viscosupplementation, and high molecular weight hyaluronic acid in different combinations. Standardized mean difference (SMD) in VAS for pain relief and Lequesne index for functional outcomes while risk ratio (RR) for complications was used for data pooling. RESULTS: Four studies comprising 185 and 189 patients in HMWHA and control groups were included, respectively. SMD for VAS and Lequesne index was -0.056 and -0.114, respectively while RR for complication was 0.879. CONCLUSIONS: Intra-articular HMWHA injection provided pain relief, functional improvement, and no severe complications on immediate short term basis. However, the results do not favor treatment with HMWHA over other treatment methods. Randomized trials are further necessary to provide data regarding comparisons between HMWHA for hip osteoarthritis concerning clinicians' convenience, compliance, duration of relief, and cost-effectiveness.

EULAR recommendations for intra-articular therapies.

OBJECTIVES: To establish evidence-based recommendations to guide health professionals using intra-articular therapies (IAT) in adult patients with peripheral arthropathies. METHODS: A multidisciplinary international task force established the objectives, users and scope and the need for background information, including systematic literature reviews) and two surveys addressed to healthcare providers and patients throughout Europe. The evidence was discussed in a face-to-face meeting, recommendations were formulated and subsequently voted for anonymously in a three-round Delphi process to obtain the final agreement. The level of evidence was assigned to each recommendation with the Oxford levels of evidence. RESULTS: Recommendations focus on practical aspects to guide health professionals before, during and after IAT in adult patients with peripheral arthropathies. Five overarching principles and 11 recommendations were established, addressing issues related to patient information, procedure and setting, accuracy, routine and special aseptic care, safety issues and precautions to be addressed in special populations, efficacy and safety of repeated joint injections, use of local anaesthetics and aftercare. CONCLUSION: We have developed the first evidence and expert opinion-based recommendations to guide health professionals using IAT. We hope that these recommendations will be included in different educational programmes, used by patient associations and put into practice via scientific societies to help improve uniformity and quality of care when performing IAT in peripheral adult joints.

A New Cross-Linked Hyaluronic Acid Gel for Preventing Adhesion After Thyroid Surgery: An Animal Study.

BACKGROUND: Revision of any neck surgeries is usually associated with increased rate of complications compared to the initial surgery due to adhesions. Especially, recurrent laryngeal nerve injury and hypoparathyroidism are most important postoperative complications of thyroid revision surgery. This study aimed to reveal anti-adhesive effects of cross-linked hyaluronic acid gel (NCHAG) in thyroid surgery. MATERIALS AND METHODS: This study was performed in 16 adult male rats who underwent hemithyroidectomy in the right lobe and randomized into two experimental groups: Group I (control group) was given any substance and Group II (NCHA group) received NCHA spray into their perithyroidal area. The rats were sacrificed after three weeks of thyroidectomy for assessment. RESULTS: Gross adhesions score (x̄ = 2.500) was significantly higher in Group I than Group II (x̄=1.750; P = 0.031). Group II showed significantly less fibrosis compared to the Group I (P = 0.002). The rate of inflammation was found to be significantly higher in group I (P = 0.008). Vascular proliferation was not different between two groups (p=0.083). CONCLUSIONS: Our study showed that NCHA can reduce postoperative adhesion and might be effective in preventing fibrosis after the thyroidectomy. Although this study could not demonstrate that application of NCHA is able to reduce complication rate in revision neck surgery, it could be safely used after thyroidectomy and neck surgeries to prevent adhesions.

Differential characteristics and management of pseudoseptic arthritis following hyaluronic acid injection is a rare complication: a systematic review.

IMPORTANCE: Acute pseudoseptic arthritis is a rare complication of hyaluronic acid (HA) injections that is not well documented in the literature. Practitioners initially suspect the symptoms of this complication to represent septic arthritis, cautiously prescribing antibiotics. This review identifies that time to presentation of symptoms postinjection, negative cell cultures and lack of crystallisation could be used as differentials to suspect pseudoseptic arthritis and to prescribe anti-inflammatory drugs while closely monitoring change of symptoms. OBJECTIVE: The purpose of this study was to describe the presentation, diagnosis and treatment of pseudoseptic arthritis. EVIDENCE REVIEW: A systematic review of the literature was conducted for studies reporting the use of HA injections for osteoarthritis resulting in pseudoseptic arthritis using the electronic databases MEDLINE, Embase and PubMed. Pertinent data were abstracted from the search yield. A unique case of a pseudoseptic reaction is also presented. FINDINGS: A total of 11 studies (28 cases), all of level IV and V evidence were included in this review. Reported cases of pseudoseptic arthritis in the literature present with severe joint pain (100%), effusion (100%), inability to weight-bear, functional impairment, and occasionally fever (22.2%). C reactive protein and erythrocyte sedimentation rate are generally elevated (71.4% and 85.7%, respectively), and leucocytosis above 10 000 was less common (50%). All reported cases in the literature identified aseptic growth on arthrocentesis, despite four cases (15.4%) reporting synovial leucocyte counts above 50 000. The presented case is the highest reported leucocyte count at 1 74 960 cells/mm3. CONCLUSIONS AND RELEVANCE: Acute pseudoseptic arthritis is rare, but a number of cases have been reported in the literature. A high degree of suspicion for pseudoseptic arthritis may be maintained in patients who present under 72 hours following HA injection. Initial antibiotic treatment, along with anti-inflammatory medications until cultures are confirmed to be negative at 5 days, is a cautious approach. However, the strength of this conclusion is limited by the few reported cases. Ultimately, this review is intended to inform practitioners of the symptoms, diagnosis and treatment of this complication, such that it could be safely differentiated from septic arthritis. LEVEL OF EVIDENCE: IV.

The effect of oral low molecular weight liquid hyaluronic acid combination with glucosamine and chondroitin on knee osteoarthritis patients with mild knee pain: An 8-week randomized double-blind placebo-controlled trial.

BACKGROUND: The popularity of dietary supplements for knee osteoarthritis (OA) management is on the rise; however, their effects are still debated. METHODS: This study aimed to investigate the effect of an oral low molecular weight liquid hyaluronic acid supplement in the treatment of knee OA patients with mild knee pain (visual analogue scale [VAS] ≤ 3) in Taiwan population. This was a randomized, double-blind, placebo-controlled study. Forty-seven subjects were enrolled and randomly allocated to either the A+HA or the placebo groups. The subjects were required to drink a bottle contained 20 mL of A+HA or placebo daily throughout an 8-week study period. The efficacy was assessed by using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the 36-item Short Form Survey (SF-36). RESULTS: At Week 8, significant reductions from baseline in the WOMAC pain (-2.6 ±â€Š1.68, P < .0001), stiffness (-1.2 ±â€Š1.50, P = .007), physical function (-5.8 ±â€Š4.39, P < .0001), and total (-9.4 ±â€Š5.82, P < .0001) scores were observed in the A+HA group but not in the placebo group. Significant differences in the mean change of WOMAC scores from baseline at Week 8 between groups were detected (P < .01). At Week 8, the A+HA group also showed significant improvements in SF-36 physical functioning (2.7 ±â€Š3.10, P = .001) and bodily pain (0.7 ±â€Š1.50, P < .05) domains. Although the A+HA group had a higher increase in the SF-36 total score than the placebo group but the difference was not statistically significant (2.1 ±â€Š12.75 vs 0.3 ±â€Š19.66, P = .12). CONCLUSIONS: Oral administration of low molecular weight liquid HA appeared to be effective for knee OA patients with mild knee pain (VAS ≤ 3) in the relief of knee OA symptoms, particularly in pain and physical function.Clinical Trial Registration: NCT04352322.

A randomized study protocol comparing the platelet-rich plasma with hyaluronic acid in the treatment of symptomatic knee osteoarthritis.

BACKGROUND: In recent years, intra articular injection of platelet rich plasma has attracted increasing attention. The major aim of our current randomized controlled double-blind study was to compare long-term outcomes of intra-articular injection of hyaluronic acid or platelet rich plasma in the treatment of the patients with knee osteoarthritis. METHODS: This is a kind of double-blind, randomized, prospective, and comparative clinical investigation with the allocation ratio of 1:1 and was approved by our institutional review Committee. Between 2020 and 2021, altogether 2 hundred patients will be selected to participate in our present study. We will report the randomized experiments in accordance with the guidelines of Consolidated Standards of Reporting Trials and then offer the Consolidated Standards of Reporting Trials flow chart. The inclusion criteria were: patients aged from 40 to 70 years old, patients with chief complaint history of at least 1 month and knee joint pain for nearly 6 months, need the analgesic drug treatment, and radiology confirmed knee osteoarthritis. The eligible patients would be randomly divided into 2 groups through applying the random numbers generated by computer before surgery. Outcomes after treatment were assessed using the Western Ontario and McMaster University and the scoring systems of visual analogue scale which were recorded through questionnaires accomplished via the patients prior to the first injection and then at three and six months, 1 and 2 years follow-up. Any adverse events occurred within 1 year after surgery were recorded during follow-up. RESULTS: This should suggest whether biological methods can offer more lasting outcomes than the viscosification. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry6265).

Intra-Articular Injections of Hyaluronic Acid or Steroids Associated With Better Outcomes Than Platelet-Rich Plasma, Adipose Mesenchymal Stromal Cells, or Placebo in Knee Osteoarthritis: A Network Meta-analysis.

PURPOSE: To evaluate the clinical effects of hyaluronic acid (HA), steroids, platelet-rich plasma (PRP), or adipose mesenchymal stromal cell (MSC) injections in the treatment of knee osteoarthritis (OA). METHODS: Randomized controlled trials with OA of the knee that compared HA, steroids, PRP, adipose MSC, or their combination with placebo or in head-to-head combination were identified from the MEDLINE, EMBASE, Cochrane Library, Web of Science, and SCOPUS databases up to June 30, 2019. We performed a network meta-analysis of the relevant literature to determine whether there was benefit from HA, steroids, PRP, or adipose MSC treatment as compared with placebo. RESULTS: A total of 43 trials covering 5554 patients were included. Steroids were ranked most likely to be effective for the management of pain or function, with adipose MSC and multiple PRP appearing least likely to be effective. Although no significant difference was observed among the 6 interventions, except for single PRP with respect to adverse effects, steroids and HA exhibited a lower rate of AEs compared with the placebo. In view of severe adverse effects, only single PRP was superior to placebo. Direct pairwise meta-analysis for pain relief showed that HA was superior to placebo or single PRP, but steroids had a significantly worse effect than single PRP. In addition, direct pairwise meta-analysis for adverse effects favored steroids in comparison to HA. CONCLUSIONS: The ranking statistics like surface under the cumulative ranking curve values of our network meta-analysis support the use of steroids and HA for appropriate patients with knee OA. For pain relief and AEs, steroids are most likely the best treatment, followed by HA. Single PRP, multiple PRP, and adipose MSC interventions do not result in a relevant reduction of joint pain nor improvement of joint function compared with placebo. However, treatment effect differences were small and potentially not clinically meaningful, indicating that other factors, such as cost and patient preferences, may be more important in patients with knee OA. LEVEL OF EVIDENCE: meta-analysis of non-homogenous randomized controlled trials, Level II.

Platelet-Rich Plasma Versus Hyaluronic Acid in the Treatment of Knee Osteoarthritis: A Meta-analysis of 26 Randomized Controlled Trials.

PURPOSE: To compare the effectiveness and safety of platelet-rich plasma (PRP) and hyaluronic acid (HA) in patients with adult knee osteoarthritis (KOA) and to explore the most effective and safe protocol by using a meta-analysis method. METHODS: This study was based on Cochrane methodology for conducting a meta-analysis. Only randomized controlled trials with an experimental group that used PRP and a control group that received HA were eligible for this study. The participants were adults who had KOA. The outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the visual analog scale (VAS), the EuroQol VAS, the International Knee Documentation Committee, the Tegner score, the Lequesne Scale, the Knee injury Osteoarthritis Outcome Score, satisfaction rate, and adverse events. Subgroup analyses was performed for patients with different doses, types, and times of PRP interventions and grades of OA. The Review Manager Database was used to analyze the included studies. RESULTS: Twenty-six randomized controlled trials involving 2430 patients were included. The WOMAC total scores, WOMAC physical function scores, and VAS scores of the PRP group were better than the those of the HA group at 3, 6, and 12 months. The PRP group had better WOMAC pain, WOMAC stiffness, EuroQol VAS, and International Knee Documentation Committee scores than the HA group at 6 and 12 months. There was no significant difference in adverse events between the 2 groups (relative risk 1.21, 95% confidence interval 0.95-1.54; P = .13). CONCLUSIONS: For the nonsurgical treatment of KOA, compared with HA, intra-articular injection of PRP could significantly reduce patients' early pain and improve function. There was no significant difference in adverse events between the 2 groups. PRP was more effective than HA in the treatment of KOA, and the safety of these 2 treatment options was comparable. LEVEL OF EVIDENCE: Level I, meta-analysis of Level I RCTs.