Knee osteoarthritis phenotypes based on synovial fluid immune cells correlate with clinical outcome trajectories.

BACKGROUND: Knee osteoarthritis (KOA) is a highly heterogeneous disease encompassing a wide range of clinical phenotypes. Phenotypes based on immune cells and protein pattern in synovial fluid (SF) and their relationship to clinical trajectories have not been described. OBJECTIVE: To assess phenotypes based on immune cells and protein pattern of SF in KOA. DESIGN: SF-derived immune cells were investigated in 119 patients with KOA using flow cytometry. Immune-phenotypes (iPhen) were determined by multivariate patient similarity network analysis and related to clinical trajectory (3-6 months post-sampling) along with protein pattern and macrophage chemokine receptors. RESULTS: Four iPhen were detected based on the distribution of T-lymphocytes, monocyte-macrophage lineage cells and activated CD8+ T-lymphocytes. The 'activated' phenotype (n = 17) had high T-lymphocytes but low monocyte-macrophage lineage cells and neutrophils, all highly activated, and showed improved symptoms in 70% patients. The 'lymphoid progressive' phenotype (n = 31) had high neutrophils, low lymphocytes and monocyte-macrophage lineage cells, low activation and was associated with lower pain levels. The 'myeloid progressive' phenotype (n = 35) had high NK and monocyte-macrophage lineage cells but low T-lymphocytes and activation. The 'aggressive' phenotype (n = 36) had high lymphocytes, macrophages, NK cells and neutrophils and high activation, and only 39% of patients improved during follow-up. Low CXCR4 and CCR7 expression on macrophages and high CXCL10 in SF were linked to improved clinical trajectory. CONCLUSION: We identified four immune-phenotypes that were associated with different clinical trajectories in KOA patients. How these phenotypes can be targeted therapeutically deserves further investigation.

Gender-related differences observed among immune cells in synovial fluid in knee osteoarthritis.

OBJECTIVE: There is no existing comprehensive report on the cellular composition of synovial fluids (SFs) from knee osteoarthritis (OA). We therefore aimed to characterise the immune cell composition in SFs from knee OA (KOA) and in subgroups according to gender. DESIGN: The immunophenotyping of monocyte/macrophage lineage cells, T and B cells, NK cells, neutrophils, dendritic and mast cells (MC) present in SFs from 53 patients (24 males/29 females) with KOA was performed using 6-colour flow cytometry. RESULTS: SFs from patients with OA contained 90% hematopoietic cells. Lymphocytes were the predominant cell population (44.8%) in the SFs of OA patients, with CD4+ T lymphocytes being more prevalent than CD8+ T cells (CD4+/CD8+ ratio = 1.3). Within the monocyte/macrophage lineage gating, monocytes accounted for 33.9%, macrophages 14.8%, myeloid dendritic cells 16.4%. The rest of the hematopoietic cells were comprised of neutrophils (8%), NK cells (3.8%), T regulatory cells (1.2%), plasmacytoid dendritic cells (1.1%), mast cells (0.3%). In OA females, a higher percentage of CD4+ T cells (P = 0.023), macrophages (P = 0.012), and a lower percentage of monocytes (P = 0.008) and CD8+ T cells (P = 0.002) were detected in comparison to OA males. CONCLUSIONS: Based on the immune cell composition of SFs, data mining analysis revealed distinct phenotypes (monocyte- and lymphocyte-predominant) within each gender group. This first study on the cellular complexity of SFs in KOA showed marked differences between male and female patients. The findings give a rational starting point for patient stratification according to their phenotypes, as is required for phenotype-specific treatment strategies.

[Smoking, Preoperative Activity, and Waiting Time for the Surgery Could Predict the Risk of Early Reoperation in Total Knee Arthroplastyy]. / Kourení, predoperacní aktivita a cekání na operaci by mohlo predikovat cetnost casných reoperací u pacientu s TEP kolena.

PURPOSE OF THE STUDY Information that would help physicians make decisions and improve the likelihood of achieving the desired results of medical interventions is sought as part of the concept of the individualized approach to patients. The primary purpose of our study was to identify which features determine the higher/lower likelihood of the need for early reoperation after a TKA (total knee arthroplasty). The successful preoperative identification of high risk patients could lead to the adjustment of the surgical procedure and thus lower the percentage of revision surgeries. MATERIAL AND METHODS In total, 826 patients (296 men and 530 women) were included in our prospective study; these patients underwent TKA implantation at our department between September 2010 and March 2015. The average age of the patients at the time of primary TKA implantation was 68.9 years. Over 60 preoperative and perioperative parameters were tracked and continuously recorded in our arthroplasty register. First, conventional analysis of individual parameters was carried out and odd ratios for their relationship with revision surgeries were set. Subsequently, the data were transformed into a graph and methods of complex network analysis were applied to identify such combinations of features (parameters) that would significantly separate the operated patients into homogeneous subgroups. The observed patient subgroups were then reanalyzed for parameters related to reoperations. RESULTS Thirty-three patients (4% of those studied) required early TKA revision (within 3 years of primary implantation). The most frequent reason for revision surgery was an early postoperative infection. The analysis of observed characteristics proved that the likelihood of revision surgery was by 80% lower in women in comparison with men. Other parameters associated with a higher frequency of reoperations were the level of preoperative activity, smoking and the waiting time for the first operation. Patients waiting for primary TKA implantation for more than 3 months showed a 2.7 times greater likelihood of revision surgery when compared to those who were operated within 3 months after the indication to surgery. Patients declaring medium or high activity levels (assessed by means of the UCLA scale) had a 2.1 times higher likelihood of revision surgery in comparison to patients with low physical activity levels. Smoking meant up to 3.2 times greater likelihood of revision in comparison with nonsmokers. Conversely, no correlation between a greater risk of reoperation and age, BMI (body mass index) or the level of comorbidities evaluated by means of the Charlson scale was confirmed. No correlation between the risk of revision and primary diagnosis was found either. DISCUSSION The frequency of early TKA revision surgeries (within 3 years after the primary surgery) in the evaluated sample is relatively high (4%). On the contrary, the reasons for early revisions correspond with recent publications. The risks of TKA infection overlap with the predictors of wound healing disorders to a great extent. Smoking, obesity and comorbidities decreasing the efficiency of the immune system are mentioned most frequently. Patients waiting for TKA implantation longer were more inclined to require early revision surgery too. Awareness of this fact is reflected in the tendency to shorten the waiting time for TKA surgery. A number of studies have pointed out the negative influence of longer waiting times on postoperative results. In our study, it was men who required revision most frequently, specifically the group of those having smoking and higher physical activity in their case histories. The influence of smoking on early postoperative morbidity is also well known. A significant finding is that stopping smoking can decrease the probability of early reoperation. However, we failed to explain the influence of higher physical activity. The influence of patients' age, BMI, level of comorbidities or primary diagnosis on the frequency of revision surgeries were not demonstrated. CONCLUSIONS We proved that women definitely show a lower risk of early TKA revision surgeries in comparison with men. A higher frequency of reoperations was related to modifiable factors such as smoking, longer waiting times for the primary operation, and a higher preoperative level of physical activity. A significant finding is that stopping smoking could decrease the probability of early TKA revision. Nonetheless, we do not recommend decreasing preoperative physical activity at this point; it will require further studies and verification of this finding. Also, the potential mechanism of the influence of greater preoperative load on the particular reason for revision is yet to be explained. Key words: total knee arthroplasty, complication, early reoperation, risk factors, multivariate analysis, smoking, preoperative activity, waiting times for surgery.

Odds-ratio network for postoperative factors revealing differences in the 2-year longitudinal pattern of satisfaction between women and men after total knee arthroplasty.

Timely and accurate assessments of the factors influencing satisfaction, a key indicator of success in primary total knee arthroplasty (TKA), may help improve TKA outcomes. Here we performed the longitudinal trend analysis of relation between satisfaction and 12 postoperative factors, which positively or negatively influence the patient satisfaction 2 years after TKA. In a real-world registry cohort (women/men: 1121/650), we showed similarities and differences between women and men in the contribution of postoperative factors to satisfaction 2 years after TKA as assessed by odds-ratio-similarity network. In men, the strongest negative factors were pain and complications, followed by mechanical problems. In women, the strongest negative factors were the pain and knee instability, followed by other mechanical problems, complications and low levels of sports activity. In both sexes, physical activity and the Knee Society Score (general and functional) influenced positively satisfaction; long-distance walking was associated with satisfaction only in women. A trend analysis revealed a reduction in the strength of satisfaction-related factors over 2 years of check-ups, particularly in women. Our study demonstrates that the key check-up for assessing the evolution of satisfaction in the 2 years after TKA was at 3 months in both sexes.