Intra-articular Administration Research Articles

Intra-articular administration of adrenaline plus an irrigation pump system for visibility during the arthroscopic reconstruction of multiple knee ligaments without a tourniquet.

Multiple ligament knee injuries (MLKIs) are rare but severe systemic trauma. Single surgery in the acute setting is preferred, although with an extended operation time. To avoid the complications associated with a tourniquet, we herein describe a method for visibility without a tourniquet: intra-articular administration of adrenaline plus an irrigation pump system. This is a cohort study with a level of evidence of 3. From April 2020 to February 2022, 19 patients with MLKIs were reviewed retrospectively. All patients got intra-articular administration of adrenaline plus an irrigation pump system for visibility without a tourniquet. The following parameters were assessed: visibility, range of motion, knee stability, visual analog scale (VAS) score, range of motion (ROM), Lysholm score, Tegner activity level, and International Knee Documentation Committee Subjective Knee Form (IKDC). All patients were followed up for at least 6 months. At the latest follow-up, the mean VAS score, ROM, Lysholm score, and IKDC were 1.79 ± 0.86, 121.21 ± 10.96, 88.16 ± 5.21, and 88.53 ± 5.06, respectively. The average Tegner activity level decreased significantly from preinjury to postoperation (5.16 ± 0.83 vs. 3.11 ± 0.88, P < 0.001). Of the 19 patients, 17 (89.47%) had good knee function, while only two patients (10.53%) had asymptomatic knees with positive Lachman tests. A total of 17 patients (89.47%) had good or excellent visualization during arthroscopy. Of the 19 patients, three (15.79%) required an increased fluid pressure to achieve a clear operative view. Two patients converted to tourniquet inflation due to persistent intra-articular bleeding after using shavers. The intra-articular administration of adrenaline plus an irrigation pump system is recommended as an alternative to a tourniquet to achieve a good visual field. Further evidence-based work with a larger sample is needed.

Intra-Articular Collagen Injections for Osteoarthritis: A Narrative Review

Osteoarthritis (OA) is the most frequent degenerative progressive joint disease worldwide, with the hand, hip, and knee being the most-affected joints. Actually, no treatment can alter the course of OA, and therapy is directed at reducing pain and improving function. The exogenous administration of collagen has been investigated as a possible symptomatic adjuvant or stand-alone treatment for OA. The aim of this review is to assess if intra-articular collagen administration can be considered as a valid and safe therapeutic option for OA. A search in the main scientific electronic databases to identify the available scientific articles about the effects of intra-articular collagen as an OA treatment was performed. The results of the seven included studies showed that the intra-articular administration of collagen may stimulate chondrocytes to produce hyaline cartilage and hinder the normal inflammatory response leading to fibrous tissue formation, reducing symptoms, and improving functionality. The use of type-I collagen as an intra-articular treatment for knee OA was found not only to be effective, but also safe with negligible side effects. The reported findings are strongly promising, highlighting the need for further high-quality research to confirm the consistency of these findings.

Advantages of the Use of Axial Traction Magnetic Resonance Imaging (MRI) of the Shoulder in Patients with Suspected Rota-Tor Cuff Tears: An Exploratory Pilot Study

Magnetic Resonance Imaging (MRI) with axial traction is a tool for the assessment of musculoskeletal pathology. Previous reports have demonstrated a better distribution of intra-articular contrast material. No investigations were performed to evaluate glenohumeral joint axial traction MRI in patients with suspected rotator cuff tears. This study aims to assess the morphological changes and the potential advantage of glenohumeral joint axial traction MRI without intra-articular contrast administration in patients with suspected rotator cuff tears. Eleven patients with clinical suspicion of rotator cuff tears underwent a shoulder MRI scan with and without axial traction. PD weighted images with SPAIR fat saturation technique and T1 weighted images with TSE technique were acquired in the oblique coronal, oblique sagittal and axial planes. Axial traction allowed a significant widening of the subacromial space (11.1 ± 1.5 mm vs. 11.3 ± 1.8 mm; p = 0.001) and inferior glenohumeral space (8.6 ± 3.8 mm vs. 8.9 ± 2.8 mm; p = 0.029). With axial traction, there was a significant decrease in measurements of the acromial angle (8.3 ± 10.8° vs. 6.4 ± 9.8°; p < 0.001) and gleno-acromial angle (81 ± 12.8° vs. 80.7 ± 11.5°; p = 0.020). Our investigation demonstrates for the first time significant morphological changes in the shoulder of patients with suspected rotator cuff tears who underwent a glenohumeral joint axial traction MRI.

Intraoperative Intra-articular Antibiotic Injection Reduces Infection in Shoulder Arthroplasty.

Deep infection is a debilitating complication after shoulder arthroplasty. The authors hypothesized that an intra-articular, intraoperative injection of antibiotics would result in a lower infection rate compared with intravenous antibiotics alone. Before 2007, 164 patients (group A) did not receive intra-articular antibiotics. From 2007 to 2018, 1324 patients (group B) received intra-articular antibiotics. Patients received intra-articular gentamicin at the end of surgery with the addition of 1 g of cefazolin in January 2014. Records were retrospectively reviewed for comorbidities, type of surgery, and infection. The cohort that received intra-articular antibiotics was compared with the cohort that did not to determine the effect of prophylactic intra-articular antibiotic administration in preventing infection. There was 1 deep infection in the antibiotic group compared with 5 in the non-antibiotic group (P<.001). Superficial infections developed in 2 cases of patients treated with antibiotics; there were no superficial infections in patients treated without antibiotics (P=.62). One previous study evaluated intra-articular injection of antibiotics for shoulder arthroplasty and found significantly lower rates of infection with the injection of intra-articular gentamicin. In this retrospective follow-up study, the injection of intra-articular gentamicin or gentamicin and cefazolin effectively decreased rates of postoperative infection. At mean follow-up of 399 days, intra-articular antibiotics at the time of surgery resulted in significantly fewer deep infections. Given the minimal risk of adverse events and minimal cost, this is a valid method of reducing infections in total shoulder arthroplasty. [Orthopedics. 2023;46(5):310-314.].

Intraarticular use of tranexamic acid during primary total knee arthroplasty

Background: Tranexamic acid (TXA) is effective in reduction of blood loss after major surgical procedures. In TKA surgeries, it is commonly administered intravenously. Since there are contraindications of systemic use of TXA, local/intraarticular TXA can also be used. The efficacy of both systemic and local TXA administration is demonstrated in the literature. The aim was to assess the effect of intraarticular TXA during total knee arthroplasty in terms of total blood loss and transfusion rate. Methods: A total of 50 TKA in 34 patients were included in this prospective study. Patients received one dose of intraarticular TXA of 3 g after skin closure and before deflation of the tourniquet. Results: The mean total blood loss in intra-articular TXA was 456.9 ml. None of the patients required transfusion postoperatively including those who underwent bilateral staged TKR. Mean postoperative hemoglobin loss was 1.07. Conclusions: TXA reduced blood loss and transfusion requirement. Intra-articular administration of TXA seems to be more effective in terms of reducing total blood loss and transfusion rates. We recommend administration of topical TXA in primary TKA in healthy patients to decrease perioperative blood loss.

Systematic review and meta-analysis of positive long-term effects after intra-articular administration of orthobiologic therapeutics in horses with naturally occurring osteoarthritis.

Equine veterinarians face challenges in treating horses with osteoarthritic joint pain in routine veterinary practice. All common treatment options aim to reduce the clinical consequences of osteoarthritis (OA) characterized by persistent synovitis and progressive degradation of articular cartilage. A range of joint-associated cell types and extracellular matrices are involved in the not yet entirely understood chronic inflammatory process. Regeneration of articular tissues to re-establish joint hemostasis is the future perspective when fundamental healing of OA is the long-term goal. The use of intra-articular applied biologic therapeutics derived from blood or mesenchymal stroma cell (MSC) sources is nowadays a well-accepted treatment option. Although this group of therapeutics is not totally consistent due to the lack of clear definitions and compositions, they all share a potential regenerative effect on articular tissues as described in in vivo and in vitro studies. However, the current stage of science in regenerative medicine needs to be supported by clinical reports as in fact, in vitro studies as well as studies using induced OA models still represent a fragment of the complex pathomechanism of naturally occurring OA. This systemic review aims to determine the long-term effect of orthobiologic therapeutics in horses suffering naturally occurring OA. Thereby, a meta-analysis of randomized controlled trials (RCTs) is conducted to describe the efficiency and safety of intra-articular applied orthobiologics in terms of lameness reduction in the long-term. Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines, thirteen studies met the inclusion criteria for the systemic review. Four of those studies have further been evaluated by the meta-analysis comparing the long-term effect in lameness reduction. Each study was examined for risk of bias. For data evaluation, a random-effects model was used, describing the overall outcome in a forest plot. The I2 statistic was used to assess heterogeneity. Results indicate, that orthobiologic therapies represent an effective long-term and safe OA treatment option. Due to the inhomogeneity of included studies, no statements are provided addressing specific orthobiologic therapies, affected joints, OA stage and horse's intended use. Future clinical trials should follow standardized study designs to provide comparable data.

Comparative evaluation of the efficacy and safety of intra-articular administration of hyaluronic acid and glucocorticoids in the complex therapy of osteoarthritis

Improving the treatment of knee (KN) osteoarthritis (OA) remains an urgent problem.Objective: to compare the efficacy and tolerability of intra-articular (i/a) administration of long-acting glucocorticoids (GCs) and Armaviscon®Forte and Armaviscon®Platinum hyaluronates in patients with knee OA.Material and methods. From November 2019 to April 2022, we examined and treated 60 patients (26 men and 34 women, mean age 41.32±3.71 years) suffering from primary KN OA. Study participants were randomly divided into three groups of 20 patients each. In the 1st group, a longacting GCs in combination with a local anesthetic was administered once i/a into the KN, in the 2nd – Armaviscon®Forte 2.3%, and in the 3rd – Armaviscon®Platinum 3%.Patients were examined at baseline, on the 14th and 60th day after a single injection of the drug. The intensity of pain was assessed on a visual analog scale (VAS), the Lequesne index, the KOOS, WOMAC, and EQ-5D questionnaires were used. When studying tolerability, the number of adverse reactions (ARs) was taken into account.Results. By the end of the observation period in the study groups, there was a decrease in the severity of pain and an increase in functionality with positive dynamics of the Lequesne and WOMAC indices. Both hyaluronic acid drugs had a positive effect on the functional state of the joints according to KOOS, improved the quality of life according to EQ-5D. The need for non-steroidal anti-inflammatory drugs in patients of the 2nd and 3rd groups decreased down to their complete cancellation. No adverse events requiring discontinuation of therapy have been reported. The advantage of i/a administration of hyaluronates in comparison with long-acting GCs was shown.Conclusion. In real clinical practice, in patients with symptomatic OA, i/a administration of hyaluronates allows obtaining more favorable results than the use of long-acting HA.

“COMPARISON OF POST OPERATIVE ANALGESIC EFFECT OF INTRAARTICULAR BUPIVACAINE AND ROPIVACAINE IN DAY CARE ARTHROSCOPIC KNEE SURGERY.”

Purpose: Intra-articular administration of local anesthetic drugs provides analgesia after arthroscopic knee surgery. Study was comparison of the analgesic effect of intraarticular injection of ropivacaine and bupivacaine in patients undergoing arthroscopic surgery. Double- Type of Study: blind, randomized prospective clinical study. The study included patients schedul Methods: ed for knee meniscus repair under arthroscopy divided into 2 groups to receive, intra-articularly, 30 mL of bupivacaine 0.5%(150mg), or ropivacaine 0.75%(225) solutions at the end of surgery. Postoperatively, pain was measured using a visual analog scale (VAS). Paracetamol was given when patients complained of pain. VAS Results: scores were higher in the bupivacaine group compared with the ropivacaine group. Duration of postoperative analgesia and paracetamol administration was shorter in the bupivacaine group compared with the ropivacaine group. Paracetamol consumption was signicantly lower (P &lt; .004) during the rst 24 hours in the ropivacaine group (4.00 ± 1.37) than in the bupivacaine groups (6.89 ± 1.711) : This study Conclusions documents that intra-articular ropivacaine 0.75% provides better analgesia than bupivacaine 0.5% after knee arthroscopic surgery

Creation of a Knee Joint-on-a-Chip for Modeling Joint Diseases and Testing Drugs

The high prevalence of debilitating joint diseases like osteoarthritis (OA) poses a high socioeconomic burden. Currently, the available drugs that target joint disorders are mostly palliative. The unmet need for effective disease-modifying OA drugs (DMOADs) has been primarily caused by the absence of appropriate models for studying the disease mechanisms and testing potential DMOADs. Herein, we describe the establishment of a miniature synovial joint-mimicking microphysiological system (miniJoint) comprising adipose, fibrous, and osteochondral tissue components derived from human mesenchymal stem cells (MSCs). To obtain the three-dimensional (3D) microtissues, MSCs were encapsulated in photocrosslinkable methacrylated gelatin before or following differentiation. The cell-laden tissue constructs were then integrated into a 3D-printed bioreactor, forming the miniJoint. Separate flows of osteogenic, fibrogenic, and adipogenic media were introduced to maintain the respective tissue phenotypes. A commonly shared stream was perfused through the cartilage, synovial, and adipose tissues to enable tissue crosstalk. This flow pattern allows the induction of perturbations in one or more of the tissue components for mechanistic studies. Furthermore, potential DMOADs can be tested via either "systemic administration" through all the medium streams or "intraarticular administration" by adding the drugs to only the shared "synovial fluid"-simulating flow. Thus, the miniJoint can serve as a versatile in vitro platform for efficiently studying disease mechanisms and testing drugs in personalized medicine.

Buprenorphine has a concentration-dependent cytotoxic effect on equine chondrocytes in vitro

To investigate the cytotoxic effects of 2 different concentrations of buprenorphine and compare them with bupivacaine and morphine on healthy equine chondrocytes in vitro. Primary cultured equine articular chondrocytes from 3 healthy adult horses. Chondrocytes were exposed for 0 and 2 hours to the following treatments: media (CON; negative control); bupivacaine at 2.2 mg/mL (BUPI; positive control); morphine at 2.85 mg/mL (MOR); buprenorphine at 0.12 mg/mL (HBUPRE); or buprenorphine at 0.05 mg/mL (LBUPRE). Chondrocyte viability was assessed using live/dead staining, water-soluble tetrazolium salt-8 (WST-8) cytotoxic assay, LDH assay, and flow cytometry. All continuous variables were evaluated with a mixed ANOVA with treatment, time, and their interactions as the fixed effects and each horse as the random effect. Buprenorphine showed a concentration-dependent chondrotoxic effect. The viability of chondrocytes was significantly decreased with exposure to HBUPRE and BUPI compared to CON, MOR, and LBUPRE. Negligible chondrotoxic effects were observed in healthy cultured equine chondrocytes exposed to 0.05 mg/mL of buprenorphine, whereas higher concentrations (0.12 mg/mL) showed a marked cytotoxic effect. Based on these results, low concentrations of buprenorphine appear to be safe for intra-articular administration. Further evaluation of this dose in vivo is needed before recommending its clinical use.

In vitro chondrotoxicity of bupivacaine, levobupivacaine and ropivacaine and their effects on caspase activity in cultured canine articular chondrocytes.

Bupivacaine, levobupivacaine and ropivacaine are potent, long acting, amide-type local anesthetics that have several clinical applications including intra-articular administration. The objectives of this study were to evaluate their in vitro effects on cell viability and caspase activity to elucidate whether they activate the extrinsic or intrinsic pathways of apoptosis in canine articular chondrocytes. Chondrocytes in monolayer culture were treated with culture medium as the control, or with 0.062% (0.62 mg/mL) bupivacaine, 0.062% levobupivacaine, and 0.062% ropivacaine for 24 hr. Cell viability was evaluated using the live/dead, 3-(4,5-dimehylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT), and Cell Counting Kit-8 (CCK-8) assays. Evaluation of caspase-3, caspase-8, and caspase-9 activity was performed using colorimetric assays. The MTT and CCK-8 assays were used to evaluate the effect of caspase inhibitors on local anesthetic chondrotoxicity. All three local anesthetics decreased chondrocyte viability after 24 hr (P<0.001). Apoptosis was induced through both the extrinsic and intrinsic pathways. Bupivacaine increased caspase-3, caspase-8, and caspase-9 activity (P<0.001). Levobupivacaine increased caspase-3 (P=0.03) while ropivacaine did not significantly upregulate activity for all three caspases. Caspase inhibition did not suppress bupivacaine chondrotoxicity whereas inhibition of caspase-8 and caspase-9 decreased ropivacaine chondrotoxicity and mildly attenuated levobupivacaine chondrotoxicity. In summary, the level of chondrotoxicity, the type of caspase activated, the level of caspase activation, and the response to caspase inhibitors was dependent on the type of local anesthetic. Therefore, ropivacaine may be a safer choice for intra-articular administration compared to levobupivacaine and bupivacaine.

Comparison of Combined Intraarticular and Intravenous Administration of Tranexamic Acid with Intraarticular and Intravenous Alone in Patients Undergoing Total Knee Arthroplasty without Drainage Catheter: A Clinical Trial Study.

We aimed to assess the most effective route for Tranexamic acid (TXA) administration among Intraarticular (IA), Intravenous (IV), and combined IA/IV for Total Knee Arthroplasty (TKA) surgeries. A double-blinded clinical trial was run on 147 TKA candidates. Blood loss and hemoglobin (Hb) drop were evaluated using the Gross and Nadler formula in three matched case groups administered TXA during the TKA through IV, IA, or combined IA/IV route. Tourniquet was used on all operations for controlling intraoperative blood loss. No drainage catheter was used for the cases. The combined group showed an average blood loss of 630±252 ml, which was significantly lower than that in the IV group (878±268 ml, P<0.01) and the IA group (774±288 ml, P=0.03). Furthermore, the mean Hb and hematocrit drop were significantly lower in the combined group, compared to the other two groups, 48 and 72 h postoperatively (P<0.05). The combined IA/IV route had a 28% and 19% reduction of blood loss, compared to the IV or IA methods, respectively. Therefore, using TXA via the combined IA/IV route may be more effective for reducing perioperative blood loss following TKA surgery using a tourniquet without drain placement.

Low-intensity pulsed ultrasound irradiation attenuates collagen degradation of articular cartilage in early osteoarthritis-like model mice

PurposeOsteoarthritis (OA) is a combination of degeneration and destruction of articular cartilage due to mechanical stress, secondary synovitis, and bone remodelling. In recent years, early knee OA, a preliminary stage of structural failure in OA, has attracted attention as a potential target for therapy to prevent the onset of OA. Intra-articular administration of monoiodoacetic acid (MIA) induces OA-like symptoms, and low doses of MIA induce early OA like symptoms. In this experiment, a low-dose of MIA was induced to early OA model mice, which were then irradiated with low-intensity pulsed ultrasound (LIPUS) to examine whether LIPUS improves symptoms of early OA.MethodsAfter 4 weeks of LIPUS irradiation, articular cartilage was observed at 1 and 4 weeks. The Osteoarthritis Research Society International (OARSI) scores were calculated using Safranin-O staining results. Cartilage degeneration was detected using Denatured Collagen Detection Reagent (DCDR).ResultsWe observed a significant decrease in OARSI scores in the LIPUS irradiated group at week 4. The non-LIPUS group showed widespread areas of double positivity for Type II collagen and DCDR, whereas the LIPUS group showed only a small number of DCDR-positive areas. In addition, macrophage numbers counted in the articular capsule at week 1 showed a significant decrease in the LIPUS irradiated group. Lubricin detection showed that lubricin positive cell number was significantly increased by LIPUS irradiation at week 4.ConclusionsThese results suggest that LIPUS attenuates cartilage degeneration in early OA by relieving inflammation and enhancing the inhibitory effect of lubricin on cartilage degeneration.

Autologous micro-fragmented adipose tissue injection provides significant and prolonged clinical improvement in patients with knee osteoarthritis: a case-series study

PurposeAmong the conservative strategies to manage patients with symptomatic knee osteoarthritis (OA), an innovative approach exploiting the regenerative capability of adipose tissue and its resident MSCs (Mesenchymal Stem Cells or Medicinal Signalling Cells) has been proposed with encouraging results. This study aims to demonstrate the benefits of autologous micro-fragmented adipose tissue (MAT) injection in the conservative treatment of knee osteoarthritis and whether any variables may affect the outcome. This is a case series single-centre study in which patients underwent intraarticular MAT injection without any associated procedures.MethodsBased on inclusion and exclusion criteria, 49 patients (67 Knees) were included and retrospectively analysed with a mean follow-up of 34.04 ± 13.62 months (minimum 11 – maximum 59). Patients were assessed through the WOMAC and KOOS questionnaires at baseline (pre-treatment) and 1-, 3-, 6-, 12-, 24- and 36-month follow-up. A minimal clinically important difference (MCID) of at least 7.5 points for the WOMAC pain scale and 7.2 for the WOMAC function scale compared to the baseline value was used.ResultsWOMAC and KOOS scores improved after treatment compared to baseline at all follow-ups with p < 0.001. Male gender and Kellgren-Lawrence (KL) grade 2 were associated with smaller improvement in WOMAC and KOOS scores (with respect to females and to KL grade 1, respectively) up to 24 months. The percentage of patients who reach the MCID for WOMAC pain is generally lower than that of patients who reach the MCID for WOMAC function (around 80% at all time points), but it increases significantly over time. Moreover, the baseline score of the WOMAC pain and function influence the outcome. Patients with worse symptoms are more likely to reach the MCID.ConclusionsIntra-articular knee injection of MAT for the treatment of knee osteoarthritis (KOA), recalcitrant to traditional conservative treatments, proved to be effective in a high percentage of cases. The positive association between a worse pre-operative score and a better clinical response to the treatment would support the idea that intra-articular administration of MAT could be considered in patients with very symptomatic KOA in which joint-replacement surgeries are not indicated (or accepted).Level of EvidenceIV, case series.

Targeting Vascular Endothelial Growth Factor Receptors as a Therapeutic Strategy for Osteoarthritis and Associated Pain.

Pain is the major reason that patients suffering from osteoarthritis (OA) seek medical care. We found that vascular endothelial growth factors (VEGFs) mediate signaling in OA pain pathways. To determine the specific contributions of VEGFs and their receptors (VEGFRs) to joint pathology and pain transmission during OA progression, we studied intra-articular (IA) injections of VEGF ligands into murine knee joints. Only VEGF ligands specific for the activation of VEGFR1, but not VEGFR2, induced allodynia within 30 min. Interventions in OA by inhibitors of VEGFRs were done in vivo using a preclinical murine OA model by IA injections of selective inhibitors of VEGFR1/VEGFR2 kinase (pazopanib) or VEGFR2 kinase (vandetanib). OA phenotypes were evaluated using pain-associated murine behavioral tests and histopathologic analyses. Alterations in VEGF/VEGFR signaling by drugs were determined in knee joints, dorsal root ganglia, and spinal cord by immunofluorescence microscopy. Pazopanib immediately relieved OA pain by interfering with pain transmission pathways. Pain reduction by vandetanib was mainly due to the inhibition of cartilage degeneration by suppressing VEGFR2 expression. In conclusion, IA administration of pazopanib, which simultaneously inhibits VEGFR1 and VEGFR2, can be developed as an ideal OA disease-modifying drug that rapidly reduces joint pain and simultaneously inhibits cartilage degeneration.

Current Management Strategy for Osteoarthritis Patients: a Review

A strategic approach is crucial to the management of patients with osteoarthritis (OA). It should be based on the current understanding of the pathogenesis of OA as an inflammatory disease. A review of current clinical guidelines for the management of patients with OA shows significant differences in the evaluation of pharmacological approach, especially the place of symptomatic slow-acting drugs for osteoarthritis, (SYSADOA) and a certain consensus in relation to non-pharmacological methods (primarily exercise, patient education, body weight control, various physiotherapy methods, orthotics and massage/manual therapy). It should also be taken into account the international “treat to target” recommendations, the main idea of which is careful regular monitoring of the patient’s condition and adaptation of treatment tactics depending on the response to treatment. Based on the analysis of literature data and their own clinical experience, the authors developed an algorithm for the strategy of complex therapy of OA, including the following steps: 1) pain control (2-4 weeks), 2) inflammation control (4-6 weeks); 3) control over cartilage degradation (6 weeks – 12 months). For each stage, a specific combination of systemic pharmacotherapy (non-steroidal anti-inflammatory drugs, SYSADOA), intra-articular administration of glucocorticoids and hyaluronic acid, exercises and magnetotherapy (pulsed electromagnetic field) was proposed. A staged comprehensive strategy for the treatment of patients with OA should help to achieve control over the symptoms, while minimizing the duration of NSAIDs and avoiding polypharmacy, and further achievement of inhibition of structural progression.

Combination of Intravenous and Intra-Articular Application of Tranexamic Acid and Epsilon-Aminocaproic Acid in Primary Total Knee Arthroplasty: A Prospective Randomized Controlled Trial.

There were limited randomized controlled trials (RCTs) of epsilon-aminocaproic acid (EACA) versus tranexamic acid (TXA) in total knee arthroplasty (TKA). The aim of the study was to compare the efficacy and safety of TXA and EACA in the combination of intravenous (IV) and intra-articular (IA) administration on reducing blood loss in patients following primary TKA. From January 2020 to January 2021, a total of 181 patients undergoing a primary unilateral TKA were enrolled in this prospective randomized controlled trial. Patients in the TXA group (n=90) received 20 mg/kg of intravenous TXA preoperatively, 1 g of intra-articular TXA intraoperatively, and three doses of 20 mg/kg intravenous TXA at 0, 3, 6 h postoperatively. Patients in the EACA group (n=91) received 120 mg/kg of intravenous EACA preoperatively, 2 g of intra-articular EACA intraoperatively, and three doses of 40 mg/kg intravenous EACA at 0, 3, 6 h postoperatively. The primary outcomes were total blood loss (TBL), transfusion rates and drop of hemoglobin (HB) level. The secondary outcomes included postoperative hospital stays and postoperative complications. The chi-square tests and Fisher's exact tests were utilized to compare categorical variables, while the independent-samples t-tests and Mann-Whitney tests were used to compare continuous variables. The patients who received TXA averaged less TBL than the patients who received EACA (831.83 ml vs 1065.49 ml, P=0.015), and HB drop in TXA group was generally less than that of EACA group on postoperative day 1 and 3 (20.84 ± 9.48 g/L vs 24.99 ± 9.40 g/L, P=0.004; 31.28 ± 11.19 vs 35.46 ± 12.26 g/L, P=0.047). The length of postoperative stays in EACA group was 3.66 ± 0.81day, which is longer than 2.62 ± 0.68day in TXA group (P < 0.001). No transfusions were required in either group. The risk of nausea and vomiting in TXA group was significantly higher than that in EACA group (11/90 vs 0/91, P < 0.01). Although the TBL and HB drop were slightly greater in EACA group, these results were not clinically important, given that no transfusions were required. EACA could be an alternative to TXA, especially for patients with severe nausea and vomiting after using TXA postoperatively. Further studies are needed to adjust dosage of EACA to make better comparison of the two drugs.

Effective reduction of need for non-steroid anti-inflammatory drugs on background of intra-artular introduction of sodium hyauloranate in patients with gonarthrosis

Introduction. Osteoarthritis (OA) in the Russian Federation is still not included in the list of socially significant diseases, despite the fact that this pathology limits the level of physical activity of the population more than diseases of the cardiovascular system, visual impairment and diabetes. European experts emphasize the relevance of research to develop methods to improve the effectiveness of viscosupplementary therapy in OA. The purpose of the study. To evaluate the efficacy, safety and long-term results of treatment of gonarthrosis with sodium hyaluronate.Materials and methods. The study included 180 patients with gonarthrosis with insufficient efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) on demand and oral symptomatic slow-acting drugs against osteoarthritis (SYSADOA). The patients were randomized into three groups. Group 1: 50 patients who received sodium hyaluronate (Ripart®; Ingal, Russia) intra-articularly. Group 2: 30 patients received intra-articular SYSADOA (bioactive concentrate of small marine fish). The control group consisted of 100 patients who received drugs of the SYSADOA group intramuscularly.Results. An effective reduction in pain both at rest and during movement was achieved in most patients of all groups, but the treatment groups differed statistically significantly in the speed of achieving the clinical effect and its duration. In the 1st group, a significant decrease in the VAS pain index was observed already at the 1st week and by the 3rd month it was –49.1 % (p &lt; 0.001). In the comparison and control groups, the indicators of speed, the degree of pain reduction, and the duration of the effect of therapy were also significant (p ≤ 0.050). But the effectiveness of therapy in these groups was statistically significantly lower than in patients of group 1 (p ≥ 0.050). It should be emphasized that the intra-articular administration of sodium hyaluronate provided a significant reduction in the need for patients to additionally take NSAIDs. After 3 months of therapy, only 5 patients (10 %) of this group continued to take NSAIDs (p &lt; 0.001); 20 – completely stopped taking NSAIDs (40 %) and 25 (50 %) reduced the dose of NSAIDs taken, the duration of the effect lasted up to 12 months.Conclusions. In our study, sodium hyaluronate demonstrated high efficiency in reducing pain in patients with gonarthrosis and contributed to a significant decrease in the need for patients to take NSAIDs for 12 months.

Intra-osseous infiltration of adipose mesenchymal stromal cells and plasma rich in growth factors to treat acute full depth cartilage defects in a rabbit model: Serum osteoarthritis biomarkers and macroscopical assessment.

Intra-articular infiltration of plasma rich in growth factors (PRGF) and adipose mesenchymal stromal cells (AMSCs) are known to inhibit osteoarthritis progression. However, in severely affected patients, the treatment cannot reach the deeper layers of the articular cartilage; thus, its potential is limited. To overcome this limitation, intra-osseous infiltrations have been suggested. The purpose of this study is to assess the impact of intra-osseous infiltration therapies on serum biomarkers of osteoarthritis and to assess cartilage regeneration macroscopically. A total of 80 rabbits were divided into four groups based on the intra-osseous treatment administered on the day of surgery: control, PRGF, AMSCs and a combination of PRGF + AMSCs. In addition, all groups received a single intra-articular administration of PRGF on the same day. Serum biomarker levels were measured before infiltration and 28-, 56-, and 84-days post infiltration, and macroscopical assessment was conducted at 56- and 84-days follow-up post infiltration. In the PRGF + AMSCs group, significantly lower concentrations of hyaluronic acid and type II collagen cleavage neoepitope were recorded at all time points during the study, followed by PRGF, AMSCs and control groups. Regarding macroscopical assessment, lower scores were obtained in PRGF + AMSCs group at all study times. The results suggest that the combination of intra-articular PRGF with intra-osseous PRGF or AMSCs achieves better results in rabbits with acute chondral defects and that intra-osseous infiltration is a safe procedure.

Pharmacokinetics and pharmacodynamics of intra-articular isoflupredone following administration to horses with lipopolysaccharide-induced synovitis

BackgroundIntra-articular corticosteroids, such as isoflupredone acetate, are commonly used in the treatment of joint inflammation, especially in performance horses. Following administration in a non-inflamed joints blood concentrations of isoflupredone were low and detectable for only a short period of time post-administration compared to synovial fluid concentrations. For some drugs, inflammation can affect pharmacokinetics, therefore, the goal of the current study was to describe the pharmacokinetics of isoflupredone acetate following intra-articular administration using a model of acute synovitis. Secondarily, pharmacodynamic effects, including effects on joint circumference, joint flexion, and lameness following intra-articular administration of isoflupredone acetate in the experimental model were described.MethodsSixteen horses received a single intra-articular dose of 8 mg of isoflupredone acetate or saline 12 h post-administration of lipopolysaccharide. Blood and urine samples were collected up to 72 h and synovial fluid for 28 days post-administration, drug concentrations determined by liquid chromatography- mass spectrometry and pharmacokinetic analysis performed. Joint circumference, maximum angle of pain free joint flexion and lameness were evaluated prior to and post-treatment.ResultsThe maximum isoflupredone plasma concentration was 2.45 ± 0.61 ng/mL at 2.5 ± 0.75 h and concentrations were less than the limit of quantitation by 72 h. Isoflupredone was below detectable concentrations in urine by 72 h post-administration in all horses and no longer detectable in synovial fluid by 96 h post-administration. Joint circumference was significantly decreased in the isoflupredone treatment group compared to the saline group at 24 and 48 h post drug administration. Pain free joint flexion was significantly different between the saline and isoflupredone treatment groups on day 4 post-treatment.ConclusionsSynovial fluid concentrations and maximum plasma concentrations of isoflupredone differed slightly between the current study and a previous one describing administration into a non-inflamed joint, however, the detection time of isoflupredone in blood was comparable. Effects of isoflupredone on joint circumference and degree of pain free joint flexion suggest a short duration of effect with respect to alleviation of lipopolysaccharide induced synovitis, however, results of this study support future studies of the anti-inflammatory effects of intra-articular isoflupredone acetate.