Correction to: Intraarticular application of autologous conditioned serum (ACS) reduces bone tunnel widening after ACL reconstructive surgery in a randomized controlled trial.

The Orthokine product used in the trial was donated by the manufacturer.

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.

A novel Laser Navigation System reduces radiation exposure and improves accuracy and workflow of CT-guided spinal interventions: a prospective, randomized, controlled, clinical trial in comparison to conventional freehand puncture.

PURPOSE: Phantom model evaluation and prospective randomized clinical trial to assess the clinical feasibility and benefit of using a novel Laser Navigation System (LNS) in CT-guided epidural and perineural injections in comparison to the conventional freehand procedure. METHODS: The LNS guided puncture technique was compared to the standard CT-guided freehand treatment using a phantom model and a randomized clinical trial. Spinal injections were administered by an experienced interventional team to evaluate needle placement accuracy, treatment time and radiation exposure. RESULTS: In the LNS group of the phantom model study, the needle entrance point accuracy of 0.5mm (freehand 3.1mm), needle target point accuracy of 2.0mm (freehand 3.5mm), number of control CT slices of 1.4 (freehand 2.7) and needle placement time of 5min 4s (freehand: 9min 18s) showed significant improvements compared to freehand in 60 punctures. In the clinical trial the LNS group achieved needle entrance point accuracy of 1.3mm (freehand 4.6mm), needle angulation accuracy of 0.4° (freehand 2.3°), number of control CT slices of 1.1 (freehand 1.8) and needle placement time of 6min 54s (freehand 9min 00s), showing significant improvements compared to freehand in a total of 58 CT-guided interventions. CONCLUSION: The LNS group showed significantly improved results in both study designs. Both the phantom model evaluation and the clinical trial of spinal injections showed feasibility and efficacy of using the novel LNS. Even an experienced interventional team worked with it more precise, faster and with reduced radiation exposure.

Intraarticular application of autologous conditioned serum (ACS) reduces bone tunnel widening after ACL reconstructive surgery in a randomized controlled trial.

PURPOSE: Pro-inflammatory cytokines play a pivotal role in osteoarthritis, as well as in bone tunnel widening after ACL reconstructive surgery. A new treatment option is to administer autologous conditioned serum (ACS) containing endogenous anti-inflammatory cytokines including IL-1Ra and growth factors (IGF-1, PDGF, and TGF-ß1, among others) in the liquid blood phase. The purpose of this trial was to establish whether the postoperative outcome could be affected by intraarticular application of ACS. METHODS: In a prospective, randomized, double-blinded, placebo-controlled trial with two parallel groups, 62 patients were treated. Bone tunnel width was measured by CT scans, while clinical efficacy was assessed by patient-administered outcome instruments (WOMAC, IKDC 2000) up to 1 year following the ACL reconstruction in patients receiving either ACS (Group A) or placebo (Group B). We compared the levels and dynamics of IL-1ß concentrations in the synovial liquid and examined the correlation between the levels of IL-1ß at three different postoperative points. RESULTS: Bone tunnel enlargement was significantly less (6 months: 8%, 12 months: 13%) in Group A than in Group B (6 months: 31%, 12 months: 38%). Clinical outcomes (WOMAC, IKDC 2000) were consistently better in patients treated with ACS at all data points and for all outcome parameters, and there were statistically significant differences in the WOMAC stiffness subscale after 1 year. The decrease in IL-1ß synovial fluid concentration was more pronounced in the ACS group, and values were lower, to a statistically significant degree, in the ACS group at day 10. CONCLUSION: The intraarticular administration/injection of ACS results in decreased bone tunnel widening after ACL reconstructive surgery.

Correlation between synovial fluid and serum IL-1beta levels after ACL surgery-preliminary report.

The possibility of controlling the harmful intra-articular influence of elevated interleukin (IL)-1beta synovial fluid concentration after anterior cruciate ligament (ACL) surgery could be useful. We investigated the correlation between serum and synovial fluid IL-1beta levels following ACL reconstruction. We measured IL-1beta concentration periodically in three synovial fluid and four serum samples in each of 20 patients receiving either autologous conditioned serum (ACS) containing endogenous anti-inflammatory cytokines including IL-1Ra and several growth factors (group A) or placebo (group B). A decrease in IL-1beta synovial fluid concentration appeared to be more pronounced in absolute terms in group A. In eight patients serum IL-1beta was detected on the 6th postoperative day. In four of them whose synovial fluid levels were over 10 pg/ml on the 6th postoperative day, serum IL-1beta was detected on the 10th postoperative day. The results were different in group B. Correlation between serum and synovial fluid IL-1beta appearance persists in patients after ACL surgery and ACS application. This study is an example of ACS influence on the ACL healing process controlling the IL-1beta levels on the basis of the serum IL-1beta detection.

Autologous conditioned serum in the treatment of orthopedic diseases: the orthokine therapy.

The common strategies for the treatment of patients with orthopedic diseases do not address the underlying pathogenesis. Several biologically based, local therapies aiming to influence the cytokine imbalance are either in development or in the initial stages of clinical use. A method based on exposure of blood leukocytes to pyrogen-free surfaces (e.g. glass spheres) elicits an accumulation of anti-inflammatory cytokines, including interleukin-1 receptor antagonist, and several growth factors, including insulin-like growth factor-1, platelet-derived growth factor, and transforming growth factor-beta(1), in the liquid blood phase. Based on these observations, a new therapy using cell-free, autologous conditioned serum (ACS) from the incubation of whole blood with glass spheres was developed. The injection of ACS into affected tissue(s) has shown clinical effectiveness and safety in animal models and studies, as well as in human clinical studies, for the treatment of osteoarthritis, lumbar stenosis, disc prolapse, and muscle injuries.