Macroscopic Synovial Inflammation Correlates with Symptoms and Cartilage Lesions in Patients Undergoing Arthroscopic Partial Meniscectomy: A Clinical Study.

BACKGROUND: The aim of the study was to examine the relationship among patients' characteristics, intraoperative pathology and pre/post-operative symptoms in a cohort of patients undergoing arthroscopic partial meniscectomy for symptomatic meniscal tears. METHODS: Clinical data were collected (age, sex, body mass index, time to surgery, trauma). Intraoperative cartilage pathology was assessed with Outerbridge score. Meniscal tears were graded with the ISAKOS classification. Synovial inflammation was scored using the Macro-score. Patient symptoms were assessed pre/post-operatively using the KOOS instrument. RESULTS: In the series of 109 patients (median age 47 years), 50% of the meniscal tears were traumatic; 85% of patients showed mild to moderate synovitis; 52 (47.7%) patients had multiple cartilage defects and 31 (28.4%) exhibited a single focal chondral lesion. Outerbridge scores significantly correlated with patient age, BMI and synovial inflammation. There was a correlation between severity of chondral pathology and high-grade synovial hyperplasia. Pre-operative KOOS correlated with BMI, meniscal degenerative changes and symptom duration. Obesity, time to surgery, presence of high-grade synovial hyperplasia and high-grade cartilage lesions were independent predictors of worse post-operative pain and function. CONCLUSION: We demonstrated that pre-operative symptoms and post-operative outcomes correlate with synovitis severity and cartilage pathology, particularly in old and obese patients that underwent arthroscopic partial meniscectomy. Importantly, patients with a degenerative meniscal pattern and with longer time to surgery experienced more severe cartilage damage and, consequentially, pain and dysfunction. These findings are fundamental to identify patients suitable for earlier interventions.

Do Synovial Inflammation and Meniscal Degeneration Impact Clinical Outcomes of Patients Undergoing Arthroscopic Partial Meniscectomy? A Histological Study.

The menisci exert a prominent role in joint stabilization and in the distribution of mechanical loading. Meniscal damage is associated with increased risk of knee OA. The aim of this study was to characterize the synovial membrane and meniscal tissues in patients undergoing arthroscopic partial meniscectomy for meniscal tear and to evaluate association with clinical outcomes. A total of 109 patients were recruited. Demographic and clinical data were collected. Visual Analogic Scale (VAS) measuring pain and Knee injury and Osteoarthritis Outcome Score (KOOS) were recorded at baseline and at 2-years follow-up. Histological and immunohistochemical characterizations were performed on synovial membranes and meniscal tissues. More than half of the patients demonstrated synovial mononuclear cell infiltration and hyperplasia. Synovial fibrosis was present in most of the patients; marked vascularity and CD68 positivity were observed. Inflammation had an impact on both pain and knee symptoms. Patients with synovial inflammation had higher values of pre-operative VAS and inflammation. Higher pre-operative pain was observed in patients with meniscal MMP-13 production. In conclusion, multivariate analysis showed that synovial inflammation was associated with pre-operative total KOOS scores, knee symptoms, and pain. Moreover, meniscal MMP-13 expression was found to be associated with pre-operative pain in multivariate analysis. Thus, targeting inflammation of the synovial membrane and meniscus might reduce clinical symptoms and dysfunction at the time of surgery.

Medium- to long-term clinical and functional outcomes of isolated and combined subscapularis tears repaired arthroscopically.

INTRODUCTION: The purpose of this study was twofold. First, the efficacy of arthroscopic repair in patients with full thickness, isolated subscapularis tendon tears (I-STTs) or combined subscapularis tendon tears (C-STTs) involving the rotator cuff tendons was evaluated. Second, the outcomes between these two groups were compared. The influence of age and gender on the cohort clinical outcomes was also analysed. Our hypothesis was that satisfactory functional results could be obtained arthroscopically in both groups without any influence of age or gender. MATERIAL AND METHODS: Seventy-nine patients were enrolled: 15 with I-STTs and 64 with C-STTs. The clinical outcomes were assessed using Constant and Disabilities of the Arm, Shoulder and Hand (DASH) scores, Numeric Rating Scale (NRS) for pain and Visual Analogue Scale (VAS) for satisfaction. The subscapularis strength was assessed using a comparative dynamometric bear-hug test. Group outcomes were compared, including statistical analysis. RESULTS: For each group, there were no differences regarding the subscapularis strength of the operated and non-operated shoulders. A comparison of the post- with the pre-operative outcomes showed an increase in the Constant score and a decrease in the NRS. Comparing the two groups, we found no difference in strength of the operated and non-operated shoulders, but a significant difference in relation to pre-operative Constant score and pre-operative NRS. Age was negatively correlated with both pre-operative and post-operative Constant scores. No association was found between gender and the outcomes, although the DASH score was higher in women. CONCLUSIONS: Arthroscopic repair of STTs provided functional restoration, pain relief and patient satisfaction in both groups. Age and gender did not affect the clinical outcomes achieved by arthroscopic STT repair.

ACL reconstruction using a bone patellar tendon bone (BPTB) allograft or a hamstring tendon autograft (GST): a single-center comparative study.

BACKGROUND AND AIM OF THE WORK: There is still debate on which graft is better indicated for anterior cruciate ligament (ACL) surgical reconstruction. The objective of this study was to evaluate the medium-term clinical outcomes of ACL reconstruction comparing patients managed with bone patellar tendon bone allograft (BPTB) versus patients treated with hamstring autograft (GST). METHODS: Patients enrolled during the period 2013-2016 underwent a personal interview with the use of specific evaluation questionnaires (Tegner e Lyshom, Knee Injury and Osteoarthritis Outcome Score, International Knee Documentation Committee), a clinical evaluation with the use of objective functional tests (Lachman test, pivot-shift) and a physical examination of the knee. RESULTS: In this study 43 patients were enrolled: 21 patients were treated by autograft and 22 patients by allograft. Patients who received allograft ACL reconstruction returned to normal sport activity earlier than patients operated on using autograft (11.7±10.3 vs 17.9±14.6 weeks, p<0.05). Data obtained with subjective tests, clinical and physical examination were  positive overall, with no differences observed between the two groups. Finally, 15 allograft patients and 12 autograft patients accepted to perform the proprioceptive tests: no difference was found between the two groups. CONCLUSIONS: At follow-up evaluation after ACL reconstruction, both BPTB allograft and GST autograft patient groups showed similar results at subjective, objective clinical evaluation and proprioceptive properties of the limb. In particular, the use of allogenic BPTB allowed the patients to return earlier to normal activities of daily-living and sport activity.

Conditioned media from human osteoarthritic synovium induces inflammation in a synoviocyte cell line.

AIM: Osteoarthritis (OA) is a whole joint pathology involving cartilage, synovial membrane, meniscus, subchondral bone, and infrapatellar fat pad (IFP). Synovitis has been widely documented in OA suggesting its important role in pathogenesis. The aim of this study was to investigate the role of different joint tissues in promoting synovitis. MATERIALS AND METHODS: Conditioned media (CM) from cartilage, synovial membrane, meniscus, and IFP were generated from tissues of five patients undergoing total knee replacement and used to stimulate a human fibroblast-like synoviocytes cell line (K4IM). Cytokines, chemokines, and metalloproteases release was analyzed in all CM by Bio-Plex Assay and sulfated glycosaminoglycan (GAG) content by dimethylmethylene blue assay. Gene expression of several markers was evaluated by real-time PCR in K4IM cells stimulated with the CM obtained from joint tissues. RESULTS: CM from all tissues produced high levels of IL-6, IL-8, and CCL2. CCL21, MMP-3, and -13 levels were detected in all CM except IFP. MMP-10 was present only in CM of cartilage and synovial tissues. IL-1ß, IL-15, TNF-α, CCL5, and CCL19 were undetectable. However, only K4IM cells stimulated by the CM from OA synovium showed an increase of IL-6, CXCL-8, CCL21, MMP10, and IL-1ß expression. CONCLUSION: Our study showed that K4IM might be a suitable in vitro model for evaluating different cellular pathways in OA studies. Importantly, we demonstrated that in OA, all joint tissues might be involved in the progression of synovitis with a predominant role of synovial membrane itself compared to the other joint tissues.

Inflammatory molecules produced by meniscus and synovium in early and end-stage osteoarthritis: a coculture study.

The aim of this study was to identify the molecules and pathways involved in the cross-talk between meniscus and synovium that may play a critical role in osteoarthritis (OA) pathophysiology. Samples of synovium and meniscus were collected from patients with early and end-stage OA and cultured alone or cocultured. Cytokines, chemokines, metalloproteases, and their inhibitors were evaluated at the gene and protein levels. The extracellular matrix (ECM) changes were also investigated. In early OA cultures, higher levels of interleukin-6 (IL-6) and IL-8 messenger RNA were expressed by synovium and meniscus in coculture compared with meniscus cultured alone. RANTES release was significantly increased when the two tissues were cocultured compared with meniscus cultured alone. Increased levels of matrix metalloproteinase-3 (MMP-3) and MMP-10 proteins, as well as increased release of glycosaminoglycans and aggrecan CS846 epitope, were observed when synovium was cocultured with meniscus. In end-stage OA cultures, increased levels of IL-8 and monocyte chemoattractant protein-1 (MCP-1) proteins were released in cocultures compared with cultures of meniscus alone. Chemokine (C-C motif) ligand 21 (CCL21) protein release was higher in meniscus cultured alone and in coculture compared with synovium cultured alone. Increased levels of MMP-3 and 10 proteins were observed when tissues were cocultured compared with meniscus cultured alone. Aggrecan CS846 epitope release was increased in cocultures compared with cultures of either tissue cultured alone. Our study showed the production of inflammatory molecules by synovium and meniscus which could trigger inflammatory signals in early OA patients, and induce ECM loss in the progressive and final stages of OA pathology.

Infrapatellar fat pad features in osteoarthritis: a histopathological and molecular study.

Objective: The infrapatellar fat pad (IFP) is considered a local producer of adipocytokines, suggesting a potential role in OA. The objective of this study was to evaluate the histopathological and molecular characteristics of OA IFPs compared with controls. Methods: The histopathological characteristics of IFPs were evaluated in patients undergoing total knee replacements and in control patients (without OA), considering the following parameters: presence of inflammatory cells, vascularization, adipose lobules dimension and thickness of the interlobular septa. Immunohistochemistry was performed to evaluate VEGF, monocyte chemotactic protein 1 (MCP-1) and IL-6 proteins. Quantitative real time PCR was performed to evaluate the expression levels of adipocytokines in the OA IFPs. Results: OA IFPs showed an increase in inflammatory infiltration, vascularization and thickness of the interlobular septa compared with controls. VEGF, MCP-1 and IL-6 proteins were higher in OA IFPs compared with in controls. Inflammatory infiltration, hyperplasia, vascularization and fibrosis were increased in OA IFP synovial membranes compared with in those of controls. VEGF protein levels were associated with an increased number of vessels in the OA IFPs, while MCP-1 and IL-6 protein levels were associated with higher grades of inflammatory infiltration. Leptin levels were positively correlated with adiponectin and MCP-1expression, while adiponectin positively correlated with peroxisome proliferative activated receptor gamma, MCP-1 and IFP vascularity. MCP-1 showed a positive correlation with peroxisome proliferative activated receptor gamma. IFP lobules dimensions were positively correlated with IL-6 expression and negatively with thickness of interlobular septa. VEGF mRNA levels were positively correlated with increased synovial vascularity. Conclusions: OA IFPs and synovial membranes are more inflamed, vascularized and fibrous compared with those of control patients (without OA).