Biphasic Scaffold Loaded With Autologous Cartilage Yields Better Clinical Outcome and Magnetic Resonance Imaging Filling Compared With Marrow Stimulation for Focal Osteochondral Lesions in the Knee.

PURPOSE: To evaluate the effectiveness of marrow stimulation (MS) versus biphasic scaffold loaded with autologous cartilage (scaffold) in treating focal osteochondral lesions of the knee. METHODS: In total, 54 patients with symptomatic focal chondral or osteochondral lesion in the knee were randomized to either the scaffold group or the MS group. International Knee Documentation Committee subjective score, the Knee Injury Osteoarthritis Outcome Score, and magnetic resonance imaging (MRI) were assessed preoperatively and at 1 and 2 years after operation to compare treatment outcomes. Biopsy and second-look arthroscopy were performed at 1 year postoperatively for consenting patients. RESULTS: There were 27 patients (mean age 31.33 ± 10.95 years) in the scaffold group, and 27 patients (31.74 ± 11.44) in the MS group. The scaffold group and the MS group both included 23 patients with lesions ≤12.5 × 12.5 mm2 mm in size. In addition, each group had 4 patients with lesions between than 12.5 × 12.5 mm2 and ≤12.5 × 25 mm2. Both interventions achieved significant improvement in clinical outcome scores at 2 years. The scaffold group had greater International Knee Documentation Committee score than the MS group at 2 years (93.85 ± 9.55 vs 92.11 ± 9.84) and in the Symptoms/Stiffness and Sport/Recreation subscales of Knee Injury Osteoarthritis Outcome Score at 2 years (96.57 ± 5.97 vs 93.57 ± 6.52, P < .05) and (90.2 ± 17.76 vs 82.8 ± 16.08, P < .05). CONCLUSIONS: The use of biphasic scaffold loaded with autologous cartilage in treating focal osteochondral lesions demonstrates superior clinical outcomes and better cartilage refill on magnetic resonance imaging at the 2-year follow-up compared to marrow stimulation. LEVEL OF EVIDENCE: Level I, Randomized controlled trial.

NGF facilitates ICAM-1-dependent monocyte adhesion and M1 macrophage polarization in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder in which monocytes adhering to synovial tissue differentiate into the pro-inflammatory M1 macrophage phenotype. Nerve growth factors (NGF) referred to as neurotrophins have been associated with inflammatory events; however, researchers have yet to elucidate the role of NGF in RA. Our examination of clinical tissue samples and analysis of data sourced from the Gene Expression Omnibus dataset unveiled elevated expression levels of M1 macrophage markers in human RA synovial tissue samples compared to normal tissue, with no such distinction observed for M2 markers. Furthermore, immunofluorescence data depicted increased expression levels of NGF and M1 macrophages in RA mice in contrast to normal mice. It appears that NGF stimulation facilitates macrophage polarization from the M0 to the M1 phenotype. It also appears that NGF promotes ICAM-1 production in human RA synovial fibroblasts, which enhances monocyte adhesion through the TrkA, MEK/ERK, and AP-1 signaling cascades. Our findings indicate NGF/TrkA axis as a novel target for the treatment of RA.

IL-17 promotes IL-18 production via the MEK/ERK/miR-4492 axis in osteoarthritis synovial fibroblasts.

The concept of osteoarthritis (OA) as a low-grade inflammatory joint disorder has been widely accepted. Many inflammatory mediators are implicated in the pathogenesis of OA. Interleukin (IL)-18 is a pleiotropic cytokine with versatile cellular functions that are pathogenetically important in immune responses, as well as autoimmune, inflammatory, and infectious diseases. IL-17, a proinflammatory cytokine mainly secreted by Th17 cells, is upregulated in OA patients. However, the role of IL-17 in OA progression is unclear. The synovial tissues collected from healthy donors and OA patients were used to detect the expression level of IL-18 by IHC stain. The OA synovial fibroblasts (OASFs) were incubated with recombinant IL-17 and subjected to Western blot, qPCR, and ELISA to examine IL-18 expression level. The chemical inhibitors and siRNAs which targeted signal pathways were used to investigate signal pathways involved in IL-17-induced IL-18 expression. The microRNAs which participated IL-18 expression were surveyed with online databases miRWalk and miRDB, followed by validation with qPCR. This study revealed significantly higher levels of IL-18 expression in synovial tissue from OA patients compared with healthy controls, as well as increased IL-18 expression in OASFs from rats with severe OA. In vitro findings indicated that IL-17 dose-dependently promoted IL-18 production in OASFs. Molecular investigations revealed that the MEK/ERK/miR-4492 axis stimulated IL-18 production when OASFs were treated with IL-17. This study provides novel insights into the role of IL-17 in the pathogenesis of OA, which may help to inform OA treatment in the future.

Omentin-1 ameliorates the progress of osteoarthritis by promoting IL-4-dependent anti-inflammatory responses and M2 macrophage polarization.

Osteoarthritis (OA) is a prevalent joint disease commonly associated with aging and obesity, which can lead to pain, stiffness, joint dysfunction, and disability. Omentin-1 (also called intelectin-1) is a newly discovered adipokine, which plays a protective role in suppressing the secretion of pro-inflammatory cytokines. Based on data from the Gene Expression Omnibus (GEO) dataset and clinical samples obtained at our institution revealed, determined that omentin-1 and IL-4 (an anti-inflammatory cytokine) levels were significantly lower in OA patients than in normal controls. Omentin-1 was shown to induce IL-4-depedent anti-inflammatory responses and M2 macrophage polarization in OA synovial fibroblasts via the PI3K, ERK, and AMPK pathways. Administering omentin-1 was shown to block cartilage degradation and bone erosion resulting from anterior cruciate ligament transection by inhibiting the production of pro-inflammatory cytokines and promoting M2 macrophage polarization in vivo. Our findings indicate omentin-1 as a promising therapeutic avenue for the treatment for OA.

Postoperative Rehabilitation after Anterior Cruciate Ligament Reconstruction through Telerehabilitation with Artificial Intelligence Brace during COVID-19 Pandemic.

BACKGROUND: Due to the rapid spread of the coronavirus disease-19 (COVID-19), most of the patients expressed a reluctance to undergo postoperative rehabilitation at a rehabilitation clinic. Therefore, in this scenario it was necessary to reshape the crucial role of postoperative rehabilitation of these patients. We conducted a telerehabilitation program based on an artificial intelligence brace (AI brace) which can monitor the progress of rehabilitation through an app and an internet server. Our hypothesis was that home-based telerehabilitation might provide clinical outcomes comparable to face-to-face, hospital-based rehabilitation programs in terms of effectiveness. METHODS: A retrospective cohort study enrolled patients who received anterior cruciate ligament reconstruction (ACLR) between January and September 2020. Patients were divided into two groups: the tele-AI group received telerehabilitation with an AI brace while the FTF group had face-to-face, hospital-based rehabilitation. Clinical knee functional scores and Tegner Activity Scale (TAS) were assessed and analyzed until 12 months after the operation. RESULTS: The tele-AI group had higher IKDC scores at 3 months (p = 0.0443) and 6 months (p = 0.0052) after surgery and higher KOOS scores at 1 month (p = 0.0365) and 6 months (p = 0.0375) after surgery. However, no significant difference between the two groups was detected at the end of the follow-up. The tele-AI group had higher TAS than FTF group after 1 year. CONCLUSIONS: Telerehabilitation after ACLR seems to provide a superior short-term outcome compared to hospital-based rehabilitation during the COVID-19 pandemic.

Cordycerebroside A inhibits ICAM-1-dependent M1 monocyte adhesion to osteoarthritis synovial fibroblasts.

Osteoarthritis (OA) is represented by the accumulation and adhesion of M1 macrophages into synovium tissues in the joint microenvironment and subsequent inflammatory response. Cordycerebroside A, a cerebroside compound isolated from Cordyceps militaris, exhibits anti-inflammatory activity, but has not yet been examined in M1 macrophages during OA disease. Our results indicate higher expression of M1 macrophage markers in synovium tissue from OA patients compared with normal healthy controls. Records from the Gene Expression Omnibus (GEO) data set and our clinic samples revealed higher levels of ICAM-1 (a critical adhesion molecule during OA disease) and CD86 (a M1 macrophage marker) in OA synovial tissue than in healthy tissue. The same effects were found in rats with OA induced by anterior cruciate ligament transaction (ACLT). We also found that cordycerebroside A inhibited ICAM-1 synthesis and antagonized M1 macrophage adhesion to OA synovial fibroblasts by inhibiting the ERK/AP-1 pathway. Thus, cordycerebroside A displayed novel anti-arthritic effects. PRACTICAL APPLICATIONS: Here we report a higher level of M1 macrophage markers and ICAM-1 in synovium tissue from OA patients compared with normal healthy controls by using GEO data set and our clinic samples. The same effects were revealed in rats with OA induced by ACLT. Cordycerebroside A significantly suppressed ICAM-1 production and diminished M1 macrophage adhesion to OA synovial fibroblasts. Therefore, cordycerebroside A exhibited novel anti-OA functions.

Nesfatin-1 facilitates IL-1ß production in osteoarthritis synovial fibroblasts by suppressing miR-204-5p synthesis through the AP-1 and NF-κB pathways.

The progression of osteoarthritis (OA) is mediated by adipokines, one of which is nesfatin-1, which is responsible for the production of inflammatory cytokines. However, how this molecule may affect the synthesis of the proinflammatory cytokine interleukin 1 beta (IL-1ß) in OA is unclear. Our analyses of records from the Gene Expression Omnibus (GEO) dataset and clinical specimens of synovial tissue revealed higher levels of nesfatin-1 and IL-1ß in OA samples compared with normal healthy tissue. We found that nesfatin-1 facilitates IL-1ß synthesis in human OA synovial fibroblasts (OASFs) and suppresses the generation of micro-RNA (miR)-204-5p, as the miR-204-5p levels in OA patients were lower than those in healthy controls. Nesfatin-1-induced stimulation of IL-1ß in human OASFs occurred via the suppression of miR-204-5p synthesis by the PI3K, Akt, AP-1 and NF-κB pathways. We suggest that nesfatin-1 is worth targeting in OA treatment.

Evaluating the necessity of bone augmentation for distal radius fracture fixed with a volar locking plate: a retrospective study.

BACKGROUND: Multiple approaches for fixation of distal radius fractures exist; nonetheless, there is no consensus on the optimal treatment for these injuries. Although using volar locking plates has become increasingly common as a surgical intervention, the usefulness of bone augmentation remains debatable. Therefore, this study aimed to evaluate the necessity of bone augmentation for distal radius fractures fixed with a volar locking plate. METHODS: This retrospective study enrolled patients with a single distal radius fracture treated with a volar locking plate between January 2014 and December 2016. Overall, 105 fractures were included and divided into two groups (non-bone augmentation: group 1, n = 88; bone augmentation: group 2, n = 17). Images were reviewed, and dorsal cortex collapse, volar tilting, and radial height and inclination were measured immediately after surgery and at the 6-month follow-up. RESULTS: Both groups exhibited significant differences in dorsal collapse (p < 0.001 and p = 0.001, respectively) and radial height shortening (p < 0.001 and p = 0.039, respectively); volar tilting and radial inclination did not differ significantly. There was no difference in the degree of dorsal collapse (p = 0.715) and radial height shortening (p = 0.651) between the two groups. Of the 105 fractures, 54 were identified as comminuted type according to the AO classification (A3, C2, and C3), and similar radiographic outcomes were noted. CONCLUSIONS: Volar locking plates for the treatment of distal radius fractures with or without bone augmentation do not affect the radiographic outcomes. In comminuted fractures, additional bone augmentation is unnecessary if intraoperative anatomical reduction and fixation are performed when possible.

Posterior cruciate ligament reconstruction implemented by the Ligament Advanced Reinforcement System over a minimum follow-up of 10 years.

PURPOSE: This study evaluated the long-term clinical follow-up results of patients who underwent double-bundle posterior cruciate ligament (PCL) reconstruction using the Ligament Advanced Reinforcement System (LARS). METHODS: Patients were assessed using clinical scores that included the Tegner activity level scale, the Lysholm score, and the International Knee Documentation Committee (IKDC) score. KT-1000 was adopted to assess stability. Radiographs and magnetic resonance imaging (MRI) were used to evaluate osteoarthritis and LARS condition. RESULTS: This study examined 38 patients, of which follow-up procedures were completed for 33 patients, resulting in a follow-up rate of 86.8%. The average follow-up period was 11.9 ±â€¯1.2 years (range: 10.3-14.2 years). The median scores of the clinical scales were as follows: Tegner activity score, 6 (range: five to seven); Lysholm score, 90 (range: 67-100); and IKDC score, 89.7 (range: 46-100). The median of the side-to-side difference (SSD) was four millimeters (range: 0-10 mm). In radiographs, the moderate OA rate was 6.9%. MRI results revealed that 26 patients exhibited ingrowth and 11 patients exhibited partial rupture of the LARS. With SSD ≤ 3 mm set as the standard for successful knee stabilization, the optimal cutoff point of LARS midsubstance thickness in the receiver operating characteristic (ROC) curve analysis was 14.3 mm. CONCLUSIONS: Long-term follow-up of the studied patients demonstrated the durability of LARS. However, clinical outcomes showed no enhancement using LARS, so it is not recommended for routine use in PCL reconstruction. LEVEL OF EVIDENCE: IV.

Comparison of implant failure rates of different plates for midshaft clavicular fractures based on fracture classifications.

BACKGROUNDS: The aim of our study was to investigate failure rates of reconstruction plate and non-reconstruction plate, and find the best strategy for implant selection for different fracture types for midshaft clavicular fractures. PATIENTS AND METHODS: Two hundred twenty-six consecutive patients with midshaft clavicular fractures who received open reduction and plate fixation during Jan 2012 to July 2017 were reviewed. The correlations between implant failure rates and risk factors including demographic data, fracture classifications, and implant types were analyzed. RESULTS: AO/OTA fracture classification and plate types are the most important factors affecting implant failure for midshaft clavicular fractures. Reconstruction plate had a significantly higher failure rate (53%) than that of non-reconstruction plates (3%) in comminuted midshaft clavicular (AO/OTA 15-2C) fractures (P value < 0.01). However, the difference was not significant in AO/OTA 15-2A and 2B classifications. CONCLUSION: Patients with comminuted midshaft clavicular (AO/OTA 15-2C) fractures treated with reconstruction plates had very high implant failure rates compared to non-reconstruction plates. We suggested that patients with comminuted midshaft clavicular (AO/OTA 15-2C) fractures treated with reconstruction plates need more protection and more frequent follow-up in the postoperative period.

Activity-related outcome in anterior cruciate ligament reconstruction with synthetic ligament advanced reinforcement system.

BACKGROUND: Arthroscopic anterior cruciate ligament (ACL) reconstruction with ligament advanced reinforcement system (LARS) had revealed good results with low complication and failure rate in series of studies. The specific candidates for ACL reconstruction with LARS are still unknown anyway. The purpose of this study is to evaluate the activity-related outcome in ACL reconstruction using LARS ligament. METHODS: A total of 43 unilateral arthroscopic ACL reconstructions with LARS were collected and divided into two groups: group A (preinjury Tegner score ≥ 6, n = 20) and group B (preinjury Tegner score < 6, n = 23). We had analyzed the stability of knee and functional outcome with a minimum of 2-years follow up. RESULTS: All patients were aware of improvement over the knee stability immediately after ACL reconstruction with LARS. The functional outcome of knee was improved in both groups by analysis with the Lysholm score and modified International Knee Documentation Committee (IKDC) score. The postoperative grading of the knee examination form of modified IKDC grade showed no statistical difference in both groups. CONCLUSION: Arthroscopic ACL reconstruction with LARS was encouraged as an alternative option even in high sports demand patients.