Injection Of Autologous Conditioned Serum Research Articles

Transforaminal Epidural Autologous Conditioned Serum Injection in the Treatment of Unilateral Lumbar Radicular Pain: A Randomized, Controlled, Double-Blind Clinical Trial

Background: Low back pain could related to disc herniation and managed by surgery. Also, less invasive options, including epidural corticosteroid injection, are available; however, it is associated with side effects. This study aimed to evaluate the effectiveness of autologous conditioned serum (ACS) in treating unilateral lumbar radicular pain. Materials and Methods: In this randomized, controlled, double-blind clinical trial study, a total of 68 patients received the transforaminal epidural injection, 28 patients received ACS, and 30 patients received 40 mg triamcinolone. Under fluoroscopic guidance in anterior-posterior and lateral views, a single injection of ACS or triamcinolone was done via the transforaminal epidural technique. Pain intensity was assessed with a visual analogue scale (VAS) and Oswestry disability index (ODI) at three weeks, three months, and six months. Results: A significant reduction in pain intensity was observed in patients of two groups. There was no significant difference between the two groups during the three months of the study. At the final evaluation at six months, the ACS group showed superiority over the triamcinolone based on the VAS score (P<0.05) and ODI (P=0.007). Conclusions: ACS therapy is a new effective option in treating lumbar radicular pain due to herniated disc. Since no specific complication has been reported, it can be used as a substitute for corticosteroids in such cases.

Clinical and functional evaluation of bone marrow aspirate concentrate vs autologous conditioned serum in the treatment of knee osteoarthritis.

The aim of this study was to compare the efficacy of a single Bone Marrow Aspirate Concentrate (BMAC) with a cycle of 4 Autologous Conditioned Serum (ACS) injections in the treatment of early-stage knee osteoarthritis (OA). Two groups of 12 patients with degenerative knee OA were treated with a single BMAC injection and with a cycle of 4 ACS injections respectively. Follow-up was set at baseline (t0), one-month (t1) and six-months (t2) evaluating VAS for pain, WOMAC index and range of motion (ROM). We reported a significant improvement in WOMAC after BMAC injection both at t1 (p= 0,001) as well as t2 (p< 0,001), plus a reduction of VAS values in BMAC group at six months follow-up (p = 0,024). In contrast, no significant differences in ROM between the two groups were observed. Both the approaches are safe and effective in the treatment of knee OA, with a major efficacy of BMAC.

Intratendinous Injection of Autologous Conditioned Serum for Treatment of Lateral Epicondylitis of the Elbow: A Pilot Study.

Autologous conditioned serum (ACS) has been effectively used in treatment of osteoarthritis. However, less is known about its efficacy in tendon disorders. In this pilot study, we aimed to evaluate the short- and long-term effects of intratendinous injection of ACS in lateral epicondylitis (LE) of the elbow. This prospective cohort included 42 patients with LE of the elbow who received 4 intratendinous injections of Orthokine® (Orthogen Lab Services GmbH, Düsseldorf, Germany) under local anesthesia over 2 weeks in an outpatient setting. The clinical and functional outcomes of injections were evaluated at 3 months and 1 year after the procedure. Pain was assessed using a visual analog scale (VAS) and functional assessment was made using the Mayo Elbow Performance Score (MEPS) and Oxford Elbow Score (OES). The pre-injection VAS score (7.07±1.19) improved significantly after the procedure at both 3 months (3.55±0.56, P<0.001) and 1 year (1.73±0.82, P<0.001). Similarly, the mean MEPSs were significantly different between baseline and 3 months (56.42±7.51 vs. 79.76±3.81, P<0.001) and between baseline and 1 year (56.42±7.51 vs. 94.28±4.06, P<0.001). The baseline OESs (84.17±6.07) also improved with intratendinous injection of ACS at 3 months (41.96±9.23, P<0.001) and 1 year (7.43±4.31, P<0.001). Only six patients (14.2%) had mild ecchymosis and swelling around the injection site which resolved spontaneously. ACS is a promising option for treatment of LE of the elbow, given its early onset of pain-relieving action and longlasting functional effects. These findings await confirmation by large-scale and prospective trials.

Two different regenerative injections in patients diagnosed with secondary hip osteoarthritis: A report of two cases

Non-surgical treatment options are limited in hip osteoarthritis secondary to developmental dysplasia of the hip (DDH). Treatment of Autologous Conditioned Serum (ACS) is based on the high level of anti-inflammatory cytokine production of leukocytes in peripheral blood. It is an effective treatment option which contains the cytokines and the growth factors. Platelet Rich Plasma (PRP) is a form of treatment that stimulates natural healing steps through growth factors in platelets. In this case report we aimed to present the results of ACS and PRP injection in two patients who developed secondary coxarthrosis after DDH surgery. At the 1-year follow-up examination, patient’s functional scores improved and requirement for non-steroid anti-inflammatory drugs had significantly reduced. Regenerative injections either autologous conditioned serum or platelet rich plasma treatments are safe and effective treatments and can be recommended particularly for cases of secondary hip osteoarthritis associated with DDH.

Shoulder injections with autologous conditioned serum reduce pain and disability in glenohumeral osteoarthritis: longitudinal observational study.

Currently, non-surgical treatments for glenohumeral osteoarthritis (GH-OA) mainly aim to reduce pain. Autologous conditioned serum (ACS), Orthokine, an interleukin-1 inhibitor from the patient's own blood has an anti-inflammatory effect. The objective was to determine whether intra-articular injections of this ACS improved symptoms in patients with GH-OA and delayed the need for a shoulder replacement. A total of 36 consecutive patients, 40 shoulders, with OA received up to 6-weekly intra-articular injections of ACS were included. Imaging of GH-OA, range of motion, visual analogue scale (VAS) pain, Shoulder Pain And Disability Index (SPADI), American Shoulder and Elbow Surgeons and Constant scores were assessed pre-injection and post treatment at 3 months. At a minimum of 2 years, VAS and SPADI scores and whether anyone had progressed to a shoulder replacement were recorded. Outcomes 3 months post-ACS injections demonstrated on average statistically significant improvement (P < 0.05) of all measurements: SPADI (54.3 ± 21.5 vs 43.7 ± 23.7), Constant score (50.5 ± 14.1 vs 57.1 ± 17.4), VAS pain (4.8 ± 2.2 vs 3.7 ± 2.4) and range of motion. Of these, 16 shoulders progressed to a shoulder replacement, nine cases quickly (0.6 ± 0.2 years) and seven cases were delayed by 3.1 ± 1.7 years. The other 18 cases had significant improvement in pain, SPADI (58.0 ± 19.6 to 31.8 ± 21.4; P < 0.01) scores and no progression to a shoulder replacement at 3.6 ± 1.0 years follow-up. There was no correlation of glenoid Walch score or joint space with clinical outcome parameters. ACS injections in the shoulder joint for OA can reduce pain and disability, and postpone the need for a shoulder replacement.

Efficacy of Autologous Conditioned Serum (ACS), Platelet-Rich Plasma (PRP), Hyaluronic Acid (HA) and Steroid for Early Osteoarthritis Knee: A Comparative Analysis.

Intra-articular injection therapy constituting corticosteroids, viscosupplements and blood-derived products are considered to have a key role in non-operative management of osteoarthritis knee. While corticosteroids and viscosupplements have proven short-term efficacy in early osteoarthritis; orthobiologics are gaining increased attention in osteoarthritis management. The aim of present study was thus to compare two commonly used biologics (platelet-rich plasma/PRP and autologous conditioned serum/ACS) to each other and to established therapies. After required institutional clearances, all patients presenting with early primary osteoarthritis knee who had failed initial conservative management and received only unilateral knee injection were included. Patients in the PRP group were compared to the other groups (comprising the HA/hyaluronic acid group, steroid group, and a matched cohort who had been administered ACS for the same indication earlier). Clinical outcome was evaluated using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire and Visual Analogue scale (VAS) pre-injection and at 6months. ACS and PRP did not have any significant difference in terms of either WOMAC score (p = 0.154) or VAS score at 6months (p = 0.850). The scores for both these orthobiologics were better than the control groups (HA group and Steroid group). Between the two control groups, HA group had better VAS scores as compared to the Steroid group (p = 0.008). The clinical outcomes following intra-articular injection of ACS and PRP are better than controls (HA and steroid), but a difference between the two orthobiologics could not be demonstrated. 3b.

Effect of Dextrose Prolotherapy, Platelet Rich Plasma and Autologous Conditioned Serum on Knee Osteoarthritis: A Randomized Clinical Trial.

Knee osteoarthritis (OA) is one of the common degenerative articular disorders that are related to decreased quality of life. Currently, novel biologic therapeutic approaches are introduced in the literature for OA management. In this study, the clinical efficiency of Dextrose prolotherapy, platelet-rich plasma (PRP) and autologous conditioned serum (ACS) injection on the level of pain and function in Knee OA were compared. A randomized clinical trial was directed on 92 knee OA patients. Patients were randomly divided into three groups: 30 were received dextrose prolotherapy once in a week for three weeks, 30 received autologous PRP for two times with seven days interval, and in the remaining 32 patients 2ml of ACS were injected two times every seven days. Study participants were measured through the Western Ontario and McMaster Universities (WOMAC) score, the visual analogue scale (VAS), at baseline, 1 and 6 months post-intervention. Both ACS and PRP treated patients showed improvement in pain intensity and knee function during 1 and 6 months pursue; however, this progress was more significant in the ACS group. Dextrose prolotherapy showed no substantial changes in pain and function of the affected knee in treated patients. Treatment of Knee OA with ACS and PRP injections are associated with pain reduction and knee function improvement. Not only, ACS therapy is more effective than that of PRP, but also due to its less variability in processing and less reported side effects, it could be considered as a safe and effective non-surgical alternative for OA management.

Is clinical effect of autologous conditioned serum in spontaneously occurring equine articular lameness related to ACS cytokine profile?

BackgroundBiologic’ therapies, such as autologous conditioned serum (ACS), are gaining popularity in treating orthopaedic conditions in equine veterinary medicine. Evidence is scarce regarding ACS constituents, and large inter-individual differences in cytokine and growth factor content have been demonstrated. The objective of the current study was to investigate the potential association between cytokine and growth factor content of ACS and clinical effect in harness racehorses with spontaneously occurring low-grade articular lameness. Horses received 3 intra-articular injections of ACS administered at approximately 2-week intervals. Lameness evaluation consisting of a trot-up with subsequent flexions tests was performed at inclusion and approximately 2 weeks after the last treatment (re-evaluation); horses were classified as responders when there was no detectable lameness on trot-up and a minimum of 50% reduction in flexion test scores at re-evaluation. Association between clinical outcome (responders vs. non-responders) and age, lameness grades at inclusion (both initial trot-up and after flexion tests), treatment interval, follow-up time and the ACS content of IL-1Ra, IGF-1 and TGF-β was determined by regression modelling.ResultsOutcome analysis was available for 19 of 20 included horses; 11 responded to treatment whereas 8 did not. There was considerable inter-individual variability in cytokine/growth factor content of ACS, and in the majority of the horses, the level of IL-10, IL-1β and TNF-α was below the detection limit. In the final multivariate logistic regression model, ACS content of IGF-1 and IL-1Ra was significantly associated with clinical response (P = 0.01 and P = 0.03, respectively). No association with clinical response was found for the other tested variables.ConclusionsThe therapeutic benefit of ACS may be related to higher levels of IL-1Ra and IGF-1. Our study corroborates previous findings of considerable inter-individual variability of cytokine- and growth factor content in ACS.

A Comparative Assessment of Autologous Conditioned Serum and Ozone for Knee Osteoarthritis Treatment: Mid-Term Follow up

Background: Knee osteoarthritis is a common disease associated with knee pain, physical disability, and joint stiffness. The use of non-surgical treatment methods in patients with knee osteoarthritis is important. Autologous conditioned serum (ACS) is a new regenerative therapeutic method that was investigated by a limited number of clinical trials. So far, using ACS in patients with Knee osteoarthritis remains to be controversial among physicians. Thus, the current study was carried out to compare the therapeutic effects of intra-articular ACS and ozone injections in patients with knee osteoarthritis.Materials and Methods: This prospective, double-blind randomized clinical trial was conducted among 60 patients (30= interleukin-1 receptor antagonist (IL-1Ra) group, 30= ozone group) with knee osteoarthritis, who referred to the Pain Management Clinic of Akhtar Educational Hospital during 2018 to 2019. In the IL-1Ra group, 2 ml of IL-1Ra was injected into the knee joint. The regimen protocol consisted of 4 injections, performed on the first, seventh, fourteenth, and twenty-first days of the treatment and ozone group, 10 ml of ozone (30 μg/ml) + 5 ml of lidocaine 1% were injected into the knee joint. The regimen protocol consisted of 3 injections, performed on the first day of the treatment, one month after the first injection, and two months after the first injection. The severity of pain was assessed by the patients’ self-report of pain and using the visual analog scale (VAS), before the treatment and 1, 3 and 6 months after the treatment. The Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaires were also measured at before and 6 months following treatment.Results: The changes in the VAS pain at different time periods showed statistically significant differences in the two groups, (P=0.0001). There was no significant difference between the two groups before the treatment and one month and three months after the initiation of the treatment; however, there was a significant difference between the two groups six months after the initiation of the treatment (P=0.0001). KOOS scores of symptoms, daily activities, and athletic and recreational functions were significantly higher in the IL-1Ra group, and the WOMAC scores of physical function and joint stiffness and the overall scores were significantly higher in the IL-1Ra group, (p<0.05).Conclusion: The intra-articular injection of IL-1Ra is a low-invasive, safe, effective, and long-acting method. In patients with knee osteoarthritis, clinical improvements and responses to the intra-articular IL-1Ra injection are better and longer compared to ozone injection. Therefore, it can be considered as a suitable choice in treating patients with chronic knee pain.

Regenerative Medicine for Axial and Radicular Spine-Related Pain: A Narrative Review.

Regenerative injection-based therapy has established itself as a therapeutic option for the management of a variety of painful musculoskeletal conditions. The aim of this work was to review the current literature regarding regenerative injection therapy for axial/radicular spine pain. A comprehensive literature review was conducted on the use of regenerative medicine for axial/radicular spine pain. Eligible articles analyzed the therapeutic injection effects of platelet-rich plasma (PRP), prolotherapy, or mesenchymal signaling cells (MSCs) via intradiscal, facet joint, epidural, or sacroiliac joint delivery. Regarding intradiscal PRP, there are level I/IV studies supporting its use. Regarding intradiscal prolotherapy, there are level III to IV studies supporting its use. Regarding intradiscal MSCs, there are level I/IV studies supporting its use with the exception of one level IV study that found no significant improvement at 12 months. Regarding facet joint injections with PRP, there are level I/IV studies supporting its use. Regarding facet joint injections with prolotherapy, there are level IV studies supporting its use, though the one level I study did not demonstrate any statistical significance supporting its use. Regarding epidural injections with PRP, there are level I/IV studies supporting its use. Regarding epidural injections with prolotherapy, there are level IV studies supporting its use, though the one level I study did not demonstrate statistical significance beyond 48 hours. Regarding sacroiliac joint injections with PRP, there are level I/IV studies supporting its use. Regarding sacroiliac joint injections with prolotherapy, there are level I/III studies supporting its use. Currently, there are level I studies to support the use of PRP and MSC injections for discogenic pain; facet joint injections with PRP; epidural injections of autologous conditioned serum and epidural prolotherapy; and PRP and prolotherapy for sacroiliac joint pain. One level I study showed that facet joint prolotherapy has no significant benefit. Notably, no intervention has multiple published level I studies.

Autologous conditioned serum: clinical and functional results using a novel disease modifying agent for the management of knee osteoarthritis

Objective The purpose of this study was to investigate the potential ability of autologous conditioned serum (ACS) to decrease pain and improve joint functionality in patients affected by knee osteoarthritis (OA). Methods Fifteen patients with clinical and radiological signs of OA of the knee were recruited for this study. Each patient received 4 injections of ACS (Orthokine; orthogen, Dusseldorf, Germany) at the site of OA once per week for 4 weeks. Clinical and functional evaluation was performed using the VAS scale for pain, WOMAC scale and KSS functional and clinical scores before the first injection, at one week, at two weeks, at three weeks, at one month and at six months. Statistical analysis was done with the Wilcoxon Signed-Rank Test. Results Our results show an improvement of all the evaluation scales at 6 months follow-up. Particularly, VAS scales among all patients decreased by 35.8% (p = .00148), KSS functional scores improved by 38.2% (p = .00148), KSS clinical scores improved by 28.9% (p = .00236) and WOMAC scores were reduced by 19.8% (p = .00188). Few adverse effects were observed in our sample. The most common complaint was pain and swelling in the subsequent days after performing the intra-articular injection. Only one patient reported rigidity following the injection of the ACS. Conclusion Our results, in conjunction with preexisting studies in the medical literature regarding ACS, demonstrate the viability of this therapy for the treatment of knee OA, showing positive influence on pain and joint function without significant adverse effects.

Evaluation of the autologous conditioned serum in the treatment of osteoarthritis

Aim: The present study was a retrospective study aiming to determine the effect of the autologous conditioned serum (ACS) on osteoarthritis (OA); we made this analysis by injecting it to a symmetrically involved knee.Methods: The present study comprised 33 patients (19 females, 14 males) with 66 knees and a mean age of 57.6±8.21 (range: 41-70). The patients included in the study had radiologically verified bilateral grade 2-3 OA of the knee according to Kellgren-Lawrence classification. Secondary arthritis, inflammatory joint diseases, clinically relevant hematologic or abnormal clinical chemistry values, joint instability, intra-articular corticosteroid injection within the previous 6 months, history of diabetes mellitus and body mass index greater than 30 kg/m2 were the exclusion criteria. Patients who had VAS difference more than 2 points between their knees were excluded from the study. ACS was injected twice a week for a total of 6 times in both knee joints for 3 weeks. The patients were analyzed with the Visual Analog Scale (VAS) (no pain was graded 0 and maximal pain was graded 10), the Knee Injury and Osteoarthritis Score (KOOS) (scoring ranges between 0 and 100. 0 indicates abnormally high level of knee problems, while 100 indicates a healthy knee with no problems) and the Knee Society Score (KSS) (Of the maximum 100 points, a possible 50 points are assigned to pain, 25 points to stability, and 25 points for range of motion) before the administration of the first injection and again 1 year after the last injection. Results: The pre-treatment and 1-year follow-up VAS values ​​of the patients were 7.36±0.93 (range: 5-9) and 3.27±1.23 (range: 1-6), respectively. ACS treatment showed a statistically significant decrease in VAS score (p &amp;lt;0.01). Pre-treatment and 1-year follow-up KOOS values ​​of the patients were 42.39±13.38 (range: 21-65) and 72.36±8.81 (range: 54-92), respectively. There was a statistically significant increase in the KOOS values of the patients (p &amp;lt;0.01). The pre-treatment and 1-year follow-up KSS values ​​of the patients were 42.79±10.26 (range: 14-61) and 70.61±9.32 (range: 49-84), respectively. There was a statistically significant increase in the KSS values of the patients (p &amp;lt;0.01). Conclusion: Intra-articular injection of ACS in patients with painful OA leads to significant improvements in pain severity, KOOS, KSS and DCS scores. In the light of these findings, ACS treatment may be considered as an effective and safe alternative treatment method in osteoarthritis.

Wednesday, September 26, 2018 1:00 PM – 2:00 PM Interventional Pain Management: 31. Epidural perineural injection of autologous conditioned serum is better than methylprednisolone in unilateral cervical radiculopathy at longer duration: a prospective randomized comparative study

BACKGROUND CONTEXT Cytokine molecules like IL-1 and prostaglandins are considered sensitizers of nerve root at chemical level in the pathogenesis of pain in cervical radiculopathy. Autologous conditioned xerum which contains interleukin-1 receptor antagonist (IL-1Ra) in high concentration may be a promising, new treatment option for patients with unilateral cervical radicular compression. It can be given by translaminar or transforaminal routes to the affected roots but the rationale for using a transforaminal route of injection rather than an inter-laminar route is that the injectate is delivered directly onto the target nerve root. PURPOSE To compare the efficacy of epidural perineural injection of autologous conditioned serum (ACS) with methylprednisolone (MPS) in treating unilateral cervical radiculopathy and to evaluate the treatment safety of ACS. STUDY DESIGN/SETTING A prospective randomized comparative study. PATIENT SAMPLE Two groups, ACS group (50 patients), MPS group (50 patients). Randomized with computer generated charts. OUTCOME MEASURES VAS scores for pain at 3 weeks (first follow up, 3 months (second follow-up), 6 months (third follow-up). METHODS Male or female patient aged between 30 years and 60 years with complaints of neck pain (moderate to severe as determined by VAS) and unilateral upper limb radiculopathy with radiological criteria: abnormal disc degeneration correlating with clinical findings were included and randomly divided into two groups. ACS group received autologous conditioned serum and the other group received methylprednisolone (MPS group) by transforaminal route under fluoroscopic guidance. ACS preparation -ACS was prepared by withdrawing 50 ml of blood from the patient under aseptic precautions and transferred to a centrifuge tube containing medical grade glass beads for incubation at 37°C, with 5% CO2 for 24 hours. After incubation, ACS was retrieved by centrifugation and stored at –20°C. RESULTS The ACS group had a decrease in pain by 50.70% (VAS score) at first follow-up (3 weeks), by 66.19% at second follow-up (3 months) and by 73.24% at third follow-up (6 months) compared to baseline. Group MPS had a decrease in pain by 68.12% at first follow-up, by 63.04% at second follow-up and by 58.45% at third follow-up compared to baseline. The difference between the two groups was statistically significant at first follow-up (p=.000) in favor of MPS group, but at third follow-up it was significant (P=.027) in favor of ACS. CONCLUSIONS Steroids (MPS) are effective in pain control in cervical radiculopathy for short duration but ACS improves disability and general health in long duration and is safe. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Plasma firocoxib concentrations after intra-articular injection of autologous conditioned serum prepared from firocoxib positive horses

Orthobiologics such as autologous conditioned serum (ACS) are often used to treat joint disease in horses. Because ACS is generated from the horse’s own blood, any medication administered at the time of preparation would likely be present in stored ACS, which could lead to an inadvertent positive drug test following intra-articular (IA) injection. The main objective of this study was to determine if ACS prepared from firocoxib positive horses could result in detectable plasma concentrations of the drug following IA injection. Firocoxib was administered to six horses at 0.1mg/kg PO twice at a 24h interval. Blood was obtained at 4h following the second dose and transferred to a separate syringe (Arthrex IRAP II) for ACS preparation. Plasma and ACS concentrations of firocoxib were analysed by liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). When horses were confirmed firocoxib negative, 7.5mL of ACS was injected into both tarsocrural joints. Blood samples were collected at 0, 4, 8, 12, 24, and 48h, and firocoxib concentration was measured.Mean (±standard error of the mean, SEM) plasma concentration of firocoxib 4h following the second dose was 33.3±4.72ng/mL. Mean (±SEM) firocoxib concentration in ACS was 35.4±4.47ng/mL. Fourteen days following the second and last dose of firocoxib, mean plasma concentration was below the lower limit of detection (LOD=1ng/mL) in all horses. Following IA injection of ACS, plasma concentrations of firocoxib remained below LOD at all times in all horses. ACS generated from horses with therapeutic plasma concentrations of firocoxib did not contain sufficient firocoxib to lead to a positive plasma drug test following IA administration.

Intra-Articular Injections of Autologous Conditioned Serum to Treat Pain from Meniscal Lesions.

Routine use of biological therapies is in its early stages. Techniques involve stem cells, platelet preparations, recombinant growth factors and autologous conditioned serum, often combined with surgery. The objective of this case analysis was to document effects of intra-articular autologous conditioned serum injections in outpatients with knee pain associated with meniscal defects. Autologous conditioned serum was prepared from patients’ blood by centrifugal separation from cellular components using a specialized device (EOT ® II, Orthokine). Outpatients (n=47) with heterogeneous knee meniscus lesions (76.6% traumatic knee injury) were injected once weekly (average 5.2 applications). Average age was 48.6 years (range 21–79). Oxford Knee Score and structural changes with the MRI Boston Leeds Osteoarthritis Knee Score were documented at baseline and 6 months. All analyses were performed retrospectively. In 83% patients, surgery was avoided during the 6-month observation period. Oxford Knee Score improved significantly from 29.1–44.3 (p<0.001; best possible score=48). Structural findings on MRI, measured by Boston Leeds Osteoarthritis Knee Score, showed significant improvement at 6 months (0.82–0.71, p<0.001). This retrospective study implies that intra-articular autologous conditioned serum injection may be an effective treatment option for knee pain associated with meniscal lesions. Controlled studies of autologous conditioned serum treatment for meniscal lesions are advocated.

Changes in haematological indices following local application of interleukin-1 receptor antagonist protein after tenotomy in rabbits

Interleukin-1 (IL-1) is the most important cytokine in the inflammation cascade activation in all tissues and is present in acute and chronic phases of inflammation. By blocking IL-1 binding to target cells, numerous inflammation processes are prevented. The use of autologous conditioned serum rich with IL-1 receptor antagonist protein (IL-1Ra) is a novel treatment method of tendon inflammation in domestic animals and humans. Injections of autologous conditioned serum (ACS) have demonstrated clinical efficacy and safety in animal models and humans in the treatment of osteoarthritis, disc prolapse and muscles and tendons injuries with low side effect. Neutropaenia, reduced white blood cell count, and infections or local irritations are described as side effects of IL-1 antagonist use in humans. Therefore, a study of blood changes in rabbits after local administration of IL-1Ra in the Achilles tendon tissue after iatrogenic inflammation was conducted. Interleukin-1 receptor antagonist protein was used to prevent and reduce tendon inflammation after longitudinal tenotomy. The study was done on 26 white Californian rabbits, divided into two equal groups consisting of 13 animals each; the experimental interleukin-1 receptor antagonist protein (irap) group, and the control group. In the irap group, autologous serum rich with IL-1Ra was used (Orthokine®vet irap, Alfa-Arthro, Croatia). Differences between two groups were considered significant as changes in the blood for certain blood elements atP&lt; 0.01. ThePvalue wasP= 0.0153 for the white blood cells,P= 0.00153 for neutrophils,P= 0.00017 and for platelets. In the control group, an increased platelet count was noticed in 70% of blood samples and a decreased neutrophil count was found in all of the irap group samples at the end of the study in comparison to the initial blood count prior to application.

Comparative study of non-complicated painful shoulder syndrome treatment by glucocorticoid and anesthetic combination and the factor of interleukin 1 receptor inhibition (Orthokine)

The aim of the study was to compare treatment of non-complicated painful shoulder syndrome (PSS) by injections of combines anesthetic Procain (0,5-10% Novocain) and glucocorticoid Betamethasone (Dyprospan 1 ml) (DN) and by injection of autologous conditioned serum with high content of interleukin 1 Pa receptor antagonist (Orthokine, OK). We studied proximate results within 6 months. Thirty three patients (18 males and 15 females) were included in OK group within age range 35-80 years. Seventy patients were enrolled in DN group (40 males and 30 females) within age range 35-72 years without endocrine disorders. All patients were assessed by visual analogous pain score (0-10), underwent physical exam with palpation of painful points and examination of shoulder biomechanics by the original PSS severity scale, X-ray and magnetic resonance imaging of painful shoulder joints. Injections were performed in the maximally painful areas with inflammatory changes verified by MRI. Each patient of OK group underwent 6 injections with 4-6 day interval. The same interval was for DN group, the number of injections were 3-5. In the OK group alleviation of pain and shoulder biomechanics occurred only after 3-4 injections with gradual improvement, whereas DN injections relieved pain and improved shoulder mobility already after 1-2 injections without further enhancement of the effect. Side effects were encountered in 70% of DN group patients, in 10% of them treatment was withdrawn. No side effects or allergic reactions were seen in OK group. The effect of OK occurs later, is less prominent, but tends to increase to compare with DN injections, however, OK is more safe and tolerable and may be the technique of choice in patients with PSS and endocrine disorders.

Evaluation of Two Protocols Using Autologous Conditioned Serum for Intra-articular Therapy of Equine Osteoarthritis—A Pilot Study Monitoring Cytokines and Cartilage-Specific Biomarkers

We hypothesised that shorter treatment intervals of intraarticular autologous conditioned serum (ACS) injections would more beneficially affect the synovial fluid (SF) concentrations of IL-1ra, IL-1β and cartilage biomarkers, compared with the traditional weekly treatment intervals in joints suffering from natural OA. In a randomised comparative study, 12 horses with OA were allocated to two groups (n = 6). The horses in group 1 received three intraarticular ACS injections at weekly intervals, whereas the horses in group 2 received three intraarticular ACS injections at two-day intervals. The levels of IL-1ra, IL-1β, CPII, C12C and CS 846 were determined in SF before and after ACS treatment using commercially available ELISA kits. The SF IL-1ra concentration 1 hour and 4 hours after ACS injection was significantly increased compared to baseline levels and decreased back to it within 48 hours. Comparing the SF IL-1ra, IL-1β, C12C, CS 846 and CP II levels before and 42 days after ACS treatment, group 2 showed a significant decrease in all parameters and an approximation on the levels in normal joints. These results indicate that the long-time effect of an ACS treatment given at two-day intervals is characterized by decreased SF IL1ra, IL-1β, C12C, CP II and CS 846 concentrations, which might indicate an improvement in joint inflammation and cartilage degrading processes . Further investigations with greater sample sizes have to prove if the two-day treatment interval is preferable to the widely used treatment protocol of weekly intraarticular ACS injections.

How does surgery compare with advanced intra-articular therapies in knee osteoarthritis: current thoughts.

The objectives of osteoarthritis (OA) management are to reduce pain and inflammation, slow cartilage degradation, improve function and reduce disability. Current strategies for managing knee OA include nonpharmacological interventions, oral pharmacological treatments, localized intra-articular injections, and surgery. It has become evident that the inflammatory response is a key contributor to the development and progression of knee OA. Signaling pathways involving growth factors and cytokines are being investigated for the development of new therapies that target the underlying biological processes causing the disease. This concept of 'molecular orthopedics' enables more patient-centered diagnostic and treatment strategies. In contrast to other conservative therapies, which ultimately only address OA symptoms, intra-articular injections, in particular autologous conditioned serum (ACS), provide benefits that have the potential to outweigh those of established pharmacological treatments and surgery. Surgery has historically been considered the final solution for treatment of knee OA, both by treating physicians and by patients; however, there are increasing concerns regarding the lack of randomized clinical trials providing evidence to support this opinion. Intra-articular injection of ACS has demonstrated efficacy as a treatment for knee OA in a number of studies, with a very low rate of adverse events and side effects, compared with surgery. Treatment with ACS utilizes the release of anti-inflammatory cytokines and regenerative growth factors to support the natural healing processes in the knee, and has the potential to provide a valuable alternative to surgical intervention.

Treatment of Osteoarthritis of the Knee with a Combination of Autologous Conditioned Serum and Physiotherapy: A Two-Year Observational Study.

BackgroundAutologous conditioned serum (ACS) is an autologous blood product that has shown efficacy against knee osteoarthritis (OA) in randomized controlled trials. However, there are few reports of its effectiveness in everyday practice. Here, we report clinical efficacy results from a two-year prospective observational study of patients with highly symptomatic knee OA who received ACS in conjunction with physiotherapy.Methods118 patients with unilateral knee OA (Kellgren-Lawrence grades I–IV), who were candidates for surgery but instead chose conservative treatment, were treated with a combination of four intra-articular injections of ACS (2 mL each) once weekly over four weeks and subsequent physiotherapy applied 4 weeks after ACS injection. Main endpoints of the study were pain (Numeric Rating Scale [NRS]) assessed at 0, 3, 6, 12 and 24 months, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) global score, assessed at 0 and 24 months. The effect size (Cohen’s d) was calculated for pain and WOMAC outcomes, with effect sizes >0.8 considered large.ResultsBy 3 months, there were significant improvements in pain (NRS) from baseline (-63.0%, p<0.001), which were maintained over 24 months. Mean WOMAC global score was reduced at 24 months compared to baseline (-56.9%, p<0.001), as were WOMAC subscores of pain (-86.0%, p<0.001) and function (-51.3%, p<0.001). Effect sizes for pain (>5) and WOMAC improvement (8.0–13.6) were very large. Only one patient received total knee joint replacement during the study. Clinical improvement did not correlate with gender, age, Kellgren-Lawrence grade, or body mass index.ConclusionsTreatment with ACS and physiotherapy produced a rapid decline in pain, which was sustained for the entire two years of the study. This was accompanied by a large improvement in WOMAC scores at two years. These results confirm that ACS combined with physiotherapy is an effective treatment for OA of the knee.