Background and AimsGM-CSF-dependent macrophage polarization has been demonstrated in rheumatoid arthritis (RA). Our aim was to seek diagnostic/prognostic biomarkers for undifferentiated arthritis (UA) by analyzing GM-CSF expression and source, macrophage polarization and density in joints of patients with UA evolving to RA or PsA compared with established RA or PsA, respectively.MethodsSynovial tissue (ST) from patients with UA evolving to RA (UA>RA, n=8), PsA (UA>PsA, n=9), persistent UA (UA, n=16), established RA (n=12) and PsA (n=10), and healthy controls (n=6), were analyzed. Cell source and quantitative expression of GM-CSF and proteins associated with pro-inflammatory (GM-CSF-driven) and anti-inflammatory (M-CSF-driven) macrophage polarization (activin A, TNFα, MMP12, and CD209, respectively) were assessed in ST CD163+ macrophages by multicolor immunofluorescence. GM-CSF and activin A levels were also quantified in paired synovial fluid samples. CD163+ macrophage density was determined in all groups by immunofluorescence.ResultsSynovial stromal cells (FAP+ CD90+ fibroblast, CD90+ endothelial cells) and CD163+ sublining macrophages were the sources of GM-CSF. ST CD163+ macrophages from all groups expressed pro-inflammatory polarization markers (activin A, TNFα, and MMP12). Expression of the M-CSF-dependent anti-inflammatory marker CD209 identified two macrophage subsets (CD163+ CD209high and CD163+ CD209low/-). CD209+ macrophages were more abundant in ST from healthy controls and PsA patients, although both macrophage subtypes showed similar levels of pro-inflammatory markers in all groups. In paired synovial fluid samples, activin A was detected in all patients, with higher levels in UA>RA and RA, while GM-CSF was infrequently detected. ST CD163+ macrophage density was comparable between UA>RA and UA>PsA patients, but significantly higher than in persistent UA.ConclusionsGM-CSF is highly expressed by sublining CD90+ FAP+ synovial fibroblasts, CD90+ activated endothelium and CD163+ macrophages in different types of arthritis. The polarization state of ST macrophages was similar in all UA and established arthritis groups, with a predominance of pro-inflammatory GM-CSF-associated markers. CD163+ macrophage density was significantly higher in the UA phases of RA and PsA compared with persistent UA. Taken together, our findings support the idea that GM-CSF is a strong driver of macrophage polarization and a potential therapeutic target not only in RA but also in PsA and all types of UA.

BACKGROUND Standard analgesic strategies for total knee arthroplasty employ local infiltration analgesia. Blockade and radiofrequency ablation of the genicular nerves are effective treatments for patients with chronic pain because of knee osteoarthritis. OBJECTIVE To test the noninferiority of the analgesic effect of genicular nerves block in comparison with local infiltration analgesia after 24 h of total knee arthroplasty. DESIGN Prospective cohort study. SETTING Perioperative setting. PATIENTS Thirty-five patients scheduled for total knee arthroplasty were prospectively included in the study and compared with 35 patients in a retrospective cohort. INTERVENTION Genicular nerve blocks in the prospective cohort were compared with local infiltration analgesia in the retrospective cohort. MAIN OUTCOME MEASURES The pain numeric rating scale and the cumulative opioid consumption in oral morphine equivalents during the first 24 h. RESULTS We conducted propensity score-matched analyses of patients using acute postoperative pain-related risk covariates. After one-to-one propensity score matching, 21 patients were included in the local infiltration analgesia group and 21 in the genicular nerve block group. The median difference in numeric rating score at rest at 24 h was −0.99 [95% confidence interval (CI), −1.99 to 0.5, P = 0.012] on the unmatched cohort and −1.9 (95% CI, −2 to 0, P = 0.002) on the matched cohort (meeting the noninferiority criteria, Δ=1). The median difference in cumulative opioid consumption was 2.5 mg (95% CI, −13.5 to 2.5, P < 0.001) for the unmatched cohort and 4.99 mg (95% CI, −11.5 to 2.5, P < 0.001) on the matched group (meeting the noninferiority criteria, Δ = 21 mg). CONCLUSION Local infiltration analgesia and genicular nerve block are comparable in terms of analgesic results. Therefore, genicular nerves block is an alternative to local infiltration analgesia in patients undergoing total knee arthroplasty. TRIAL REGISTRATION Clinicaltrials.gov identifier: NCT04024319.

Background: Patients with severe knee osteoarthritis are evaluated for total knee replacement (TKR), whose main indications are persistent pain and severe functional limitations substantially affecting mobility. However, evaluation of pain intensity and functional disability is difficult to standardize. Objective: To evaluate the relationship between quadriceps muscle thickness (QMT) and quality; the QMT and subcutaneous fat thickness (SFT) and QMT and function in patients with knee OA on a waiting list for TKR. Methods: Cross-sectional study in consecutively-enrolled patients. Variables: SFT, QMT and rectus femoris muscle quality, assessed by echointensity (EI). Function by the Timed Up & Go Test (TUG); sociodemographic and clinical variables and physical activity were determined. Karl Pearson correlations and multiple linear regression were used. Results: 61 patients (45 female, mean age 69.7 years [SD 7.2], mean BMI 33.0 [SD 5.7], mean comorbidities 3.3 [SD 2.0], 52.5% regular physical activity) were studied. Mean TUG was 15.1 (SD 6.1). Variables retained in the regression model explained 36% of variability in the TUG. Greater muscle content (percentage) (r = À0,291) was associated with better TUG scores (p = 0.001). Greater muscle EI was negatively (r = À0,364) associated with function (p = 0.006). Older age was associated with worse TUG scores while regular physical activity was associated with better TUG scores (p = 0.001 and p = 0.008, respectively). Conclusions: A higher percentage of quadriceps muscle and better muscle quality (lower EI) was associated with better function. Age and exercise levels influenced function. Ultrasound may provide © 2017

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