Infrapatellar fat pad adipose tissue-derived macrophages display a predominant CD11c+CD206+ phenotype and express genotypes attributable to key features of OA pathogenesis.

Objectives: In knee osteoarthritis (OA), macrophages are the most predominant immune cells that infiltrate synovial tissues and infrapatellar fat pads (IPFPs). Both M1 and M2 macrophages have been described, but their role in OA has not been fully investigated. Therefore, we investigated macrophage subpopulations in IPFPs and synovial tissues of knee OA patients and their correlation with disease severity, examined their transcriptomics, and tested for factors that influenced their polarization. Methods: Synovial tissues and IPFPs were obtained from knee OA patients undergoing total knee arthroplasty. Macrophages isolated from these joint tissues were characterized via flow cytometry. Transcriptomic profiling of each macrophage subpopulations was performed using NanoString technology. Peripheral blood monocyte-derived macrophages (MDMs) were treated with synovial fluid and synovial tissue- and IPFP-conditioned media. Synovial fluid-treated MDMs were treated with platelet-rich plasma (PRP) and its effects on macrophage polarization were observed. Results: Our findings show that CD11c+CD206+ macrophages were predominant in IPFPs and synovial tissues compared to other macrophage subpopulations (CD11c+CD206-, CD11c-CD206+, and CD11c-CD206- macrophages) of knee OA patients. The abundance of macrophages in IPFPs reflected those in synovial tissues but did not correlate with disease severity as determined from Mankin scoring of cartilage destruction. Our transcriptomics data demonstrated highly expressed genes that were related to OA pathogenesis in CD11c+CD206+ macrophages than CD11c+CD206-, CD11c-CD206+, and CD11c-CD206- macrophages. In addition, MDMs treated with synovial fluid, synovial tissue-conditioned media, or IPFP-conditioned media resulted in different polarization profiles of MDMs. IPFP-conditioned media induced increases in CD86+CD206+ MDMs, whereas synovial tissue-conditioned media induced increases in CD86+CD206- MDMs. Synovial fluid treatment (at 1:8 dilution) induced a very subtle polarization in each macrophage subpopulation. PRP was able to shift macrophage subpopulations and partially reverse the profiles of synovial fluid-treated MDMs. Conclusion: Our study provides an insight on the phenotypes and genotypes of macrophages found in IPFPs and synovial tissues of knee OA patients. We also show that the microenvironment plays a role in driving macrophages to polarize differently and shifting macrophage profiles can be reversed by PRP.

Intraoperative Surgeon-Performed versus Conventional Anesthesiologist-Performed Continuous Adductor Canal Block in Total Knee Arthroplasty: A Randomized Controlled Trial.

A continuous adductor canal block (cACB) for pain control in total knee arthroplasty (TKA) is always performed by an anesthesiologist. A surgeon-performed cACB during surgery is somewhat questionable in terms of feasibility, reproducibility, and efficacy. This study was divided into two phases. In Phase 1 study, an experimental dissection of 16 cadaveric knees to expose the saphenous nerve and related muscles around the adductor canal was conducted. The extent of dye after injection via a catheter inserted into the adductor canal at the time of TKA was evaluated. In Phase II, a randomized controlled trial study comparing clinical outcomes between surgeon-performed (Group 1) and anesthesiologist-performed cACB (Group 2) during TKA in 63 patients was evaluated. The visual analogue scale (VAS) at rest and during movement at several time points and functional outcomes during hospitalization were compared. The Phase I study demonstrated surgeon-performed cACB during surgery feasible and reproducible with consistent dye extension into the adductor canal after injection via a catheter. In the Phase II study, 29 patients of Group 1 and 30 patients of Group 2 completed the evaluation with no differences in baseline parameters. The VAS during movement at 24 and 36 hours, quadriceps strength, time up and go test, and knee motion at different time points, and total morphine consumption showed no differences between both groups. There were no procedure-related complications. The surgeon-performed cACB during surgery was feasible and reproducible with similar VAS scores and functional outcomes during hospitalization to anesthesiologist cACB. Level of evidence is Level I, prospective randomized trial.

The Immunological Facets Of Chondrocytes In Osteoarthritis: A Narrative Review.

Osteoarthritis (OA) is a disease in which the pathogenesis affects the joint and its surrounding tissues. Cartilage degeneration is the main hallmark of OA and chondrocytes within the cartilage regulate matrix production and degradation. In OA patients and animal models of OA, the pathology of the disease relates to disequilibrium between anabolic and catabolic states of the cartilage. Moreover, chondrocyte phenotype and function are also immunologically altered. Under inflammatory conditions, chondrocytes increase production levels of inflammatory cytokines and cartilage-degrading enzymes, which further drive cartilage destruction. Chondrocytes also have an innate immune function and respond to DAMPs and cartilage fragments via innate immune receptors. In addition, chondrocytes play a role in adaptive immune responses by acting as antigen presenting cells and presenting cartilaginous antigens to T cells. Indirectly, chondrocytes are stimulated by pathogen-associated molecular patterns (PAMPs) present in the joints, a result of the microbiota in the host. Chondrocytes have both direct and indirect relationships with immune cells and the immune compartment of OA patients. Therefore, chondrocytes serve as a target for immunotherapeutic approaches in OA. In this narrative review, we cover the aforementioned immune-related aspects of chondrocytes in OA.

Intraoperative landmark-based genicular nerve block versus periarticular infiltration for postoperative analgesia in total knee arthroplasty: a randomized non-inferiority trial.

INTRODUCTION: Genicular nerve blocks (GNBs) are an emerging technique that have been used as a part of multimodal analgesia for total knee arthroplasty. The efficacy of intraoperative landmark-based GNBs, a recently introduced technique, has been established. We hypothesized that it would provide non-inferior postoperative analgesia compared with periarticular infiltration (PAI) when combined with continuous adductor canal block. METHODS: This study randomized 140 patients undergoing total knee arthroplasty to receive either intraoperative landmark-based GNB (GNB group) or PAI (PAI group), with 139 completing the study. The primary outcomes were the pain scores at rest and during movement at 12 hours postoperatively on an 11-point Numerical Rating Scale; the non-inferiority margin was 1. Pain scores at additional time points, intravenous morphine consumption, time to first rescue analgesia, functional performance and muscle strength tests, and sleep disturbance were also assessed. RESULTS: At 12 hours postoperatively, the PAI and GNB groups had median resting pain scores of 0 (0-2) and 0 (0-2), respectively. The median difference was 0 (95% CI -0.4 to 0.4, p=1), with the 95% CI upper limit below the prespecified non-inferiority margin. The median pain score during movement was 1.5 (0-2.3) and 2 (1-3.1) in the PAI and GNB groups, respectively. The median difference was 0.9 (95% CI 0.3 to 1.6, p=0.004), failing to demonstrate non-inferiority. The GNB group had higher intravenous morphine consumption at 12 hours postoperatively and a shorter time to first rescue analgesia. CONCLUSIONS: GNB compared with PAI provides non-inferior resting pain relief. Non-inferiority was not established for pain during movement. TRIAL REGISTRATION NUMBER: TCTR20220406001 (www.thaiclinicaltrials.org).

Using a discrete choice experiment to elicit patients' preferences and willingness-to-pay for knee osteoarthritis treatments in Thailand.

Osteoarthritis is the most common type of joint disease among elderly patients around the world. In response to the need for patient-centered care, patients' and physicians' preferences for knee osteoarthritis treatments have been studied in multiple countries, but not in Thailand. The objective of this study was to investigate Thai patients' preferences and their willingness to pay (WTP) for knee osteoarthritis treatments by using a discrete choice experiment (DCE). Six knee osteoarthritis treatment attributes, including pain relief, delayed disease progression, gastrointestinal side effects, kidney side effects, cardiovascular side effects, and cost, were used to develop a paper-based, DCE questionnaire survey. Patients with knee osteoarthritis, who were at least 18 years old and who provided written informed consent, were recruited from the orthopedic department in a tertiary care hospital in Thailand via convenience sampling. The conditional logit model was used to determine patients' preferences and WTP. The Institutional Review Board at Chulalongkorn University approved this study before it started. A total of 232 patients were collected and analyzed in this study. Patients preferred treatments with a higher efficacy (pain relief and delayed disease progression), a lower probability of side effects (gastrointestinal, kidney, and cardiovascular side effects), and a lower cost. Regarding efficacy and side effects, the patients weighted the importance of a 1% change in cardiovascular side effects (- 0.08) more heavily than 1% changes in kidney (- 0.07) and gastrointestinal (- 0.02) side effects, delayed disease progression (0.02), and pain relief (0.01). Patients were willing to pay 29.56 Thai Baht (THB) and 41.84 THB per month for every 1% increase in pain relief and delayed disease progression, respectively. Conversely, patients were willing to pay 52.04 THB, 145.18 THB and 164.23 THB per month for every 1% decrease in gastrointestinal, kidney, and cardiovascular side effects, respectively. In conclusion, pain relief, delayed disease progression, gastrointestinal side effects, kidney side effects, cardiovascular side effects, and the cost of treatment were significant factors among patients undergoing knee osteoarthritis treatment. Additionally, patients had a higher WTP for delayed disease progression than pain relief and a higher WTP for a reduced probability of cardiovascular side effects than gastrointestinal and kidney side effects. These findings could be used to support treatment decisions for knee osteoarthritis patients in Thailand.

Comparison of Analgesic Efficacies of the iPACK (Interspace Between the Popliteal Artery and Capsule of the Posterior Knee) and Genicular Nerve Blocks Used in Combination With the Continuous Adductor Canal Block After Total Knee Arthroplasty: A Randomized Clinical Trial.

BACKGROUND: The interspace between the popliteal artery and capsule of the posterior knee (iPACK) block and the genicular nerve block (GNB) are motor-sparing nerve blocks used for knee pain relief. We compared the analgesic efficacies of ultrasound-guided iPACK block and GNB when combined with continuous adductor canal block after total knee arthroplasty. METHODS: In this randomized control study, 132 total knee arthroplasty patients were assigned to the iPACK, GNB, and iPACK + GNB groups. All patients received combined spinal anesthesia and continuous adductor canal block. The primary outcome was the 8-hour postoperative pain score during movement. Secondary outcomes were pain scores, posterior knee pain, intravenous morphine consumption, and tibial and common peroneal nerve sensorimotor function. All included patients completed the study. RESULTS: The 4-hour and 8-hour postoperative pain scores during movement were significantly lower in the iPACK + GNB group than that in the iPACK group (-2.5 [3.6, 1.3]; P < .001 and -2 [-3, -1]; P < .001, respectively). The differences in rating pain scores and posterior knee pain were not clinically relevant. The iPACK group demonstrated a significantly higher intravenous morphine consumption than did the GNB and iPACK + GNB groups during the first 48 hours postoperatively (P < .001) but were not clinically relevant. There was no incidence of complete sensorimotor blockade in any of the groups. CONCLUSION: The iPACK-GNB combination relieved pain during movement better than the iPACK block alone during the 8 hours postoperatively after total knee arthroplasty in setting of multimodal analgesia such as adductor canal block.

Effect of Adding Perineural Methylprednisolone to Peripheral Nerve Blocks Combined With Intravenous Dexamethasone for Prolonged Postdischarge Analgesia After Fast-track Total Knee Arthroplasty: A Randomized Controlled Trial.

OBJECTIVES: Patients undergoing total knee arthroplasty (TKA) may experience moderate-to-severe subacute pain after hospital discharge that may be undermanaged. We aimed to evaluate the effect of methylprednisolone added to ultrasound-guided peripheral nerve blocks (PNBs) combined with multimodal analgesia including intravenous dexamethasone for prolonged analgesia after early discharge. MATERIALS AND METHODS: We randomized 80 patients who underwent fast-track TKA into 2 groups. All patients received a periarticular injection, PNBs, and multiple doses of intravenous dexamethasone. The methylprednisolone group received 140 mg methylprednisolone in PNBs, while the nonmethylprednisolone group did not. The primary outcome was the incidence of moderate-to-severe pain (Numerical Rating Scale ≥4) during the first 12 postdischarge days. The secondary outcomes included pain scores until 3 postoperative months, incidence of rebound pain, functional performances, patient satisfaction, and adverse events. RESULTS: No significant between-group differences were noted in the incidence of moderate-to-severe pain during the first 12 postdischarge days (nonmethylprednisolone vs. methylprednisolone groups: 70% vs. 69.2%, P=0.941). However, this incidence was significantly higher in the methylprednisolone group between 2 weeks and 1 month (P=0.015) and between 1 and 3 months (P=0.004) postoperatively. No between-group differences in the Numerical Rating Scale scores at the postdischarge time points, incidence of rebound pain, and functional performance results were noted. DISCUSSION: Adding perineural methylprednisolone to ultrasound-guided PNBs for multimodal analgesia with intravenous dexamethasone did not prolong analgesia and improved the functional ability after fast-track TKA within 12 postdischarge days. However, the incidence moderate-to-severe pain may increase between the 2-week and 3-month follow-up.

An economic evaluation of knee osteoarthritis treatments in Thailand.

Objective: The objective of this study is to evaluate the cost-effectiveness of different knee OA care sequences compared to standard treatment reimbursed by the major health insurance payer in Thailand. Method: We used decision analytical modeling to evaluate the effect of either adding etoricoxib or crystalline glucosamine sulfate compared to standard treatment from a societal perspective over patients' lifetimes. Data were analyzed based on efficacy, whereas adverse events were considered as a substate. Model input data were retrieved from relevant published literature and the Standard Cost Lists for Health Technology Assessment, Thailand. All health outcomes were measured in a unit of quality-adjusted life-year (QALY). An incremental cost-effectiveness ratio (ICER) was applied to examine the costs and QALYs. Sensitivity analysis was performed to investigate the robustness of the model. Result: The results demonstrated that adding crystalline glucosamine sulfate (before diclofenac plus proton pump inhibitors, PPI) into the standard care sequence was a dominant strategy compared to the standard care sequence. Adding etoricoxib alone or including crystalline glucosamine sulfate (after diclofenac plus PPI) was dominated by adding crystalline glucosamine sulfate (before diclofenac plus PPI), whereas in a willingness-to-pay (WTP) threshold in Thailand, adding of both crystalline glucosamine sulfate (before diclofenac plus PPI) and etoricoxib were cost-effective when compared to adding crystalline glucosamine sulfate alone with ICER of 125,547 Thai baht/QALY (3,472 US dollars/QALY). Conclusion: The addition of crystalline glucosamine sulfate and etoricoxib into standard knee OA treatment were cost-effective at the WTP threshold in Thailand. In addition, early initiation of crystalline glucosamine sulfate would be less costly and more effective than delayed treatment or the use of standard treatment alone.

Association between Common Variants in VEGFA Gene and the Susceptibility of Primary Knee Osteoarthritis.

OBJECTIVES: This study aimed to analyze the relationship between vascular endothelial growth factor A (VEGFA) gene polymorphisms, plasma VEGFA, and the susceptibility of knee osteoarthritis (OA). DESIGN: A total of 404 subjects, 202 knee OA subjects and 202 healthy volunteers, were enrolled into the study. Four distinct polymorphisms of the VEGFA gene were evaluated using polymerase chain reaction-restriction fragment length polymorphism: -2578C/A (rs699947), -1154G/A (rs1570360), -634C/G (rs2010963), and +936C/T (rs3025039). Plasma VEGFA levels were analyzed using enzyme-linked immunosorbent assay. RESULTS: The most common nucleotides in both knee OA subjects and healthy controls were CC for -2578C/A, GG for -1154G/A, CG for -634C/G, and CC for +936C/T in the VEGFA gene. Genotype distribution and allele frequencies of VEGFA -2578C/A, -1154G/A, -634C/G, and +936C/T single nucleotide polymorphisms did not differ between OA patients and the controls. Plasma VEGFA levels showed no difference between OA patients and the controls. In contrast, plasma VEGFA levels of -634C/C genotype were significantly higher in OA patients than in the controls (P = 0.035). According to the -2578A/A genotype, patients with early stage OA had a higher odds ratio than those with advanced stage OA (P = 0.023). CONCLUSIONS: VEGFA -2578C/A (rs699947), -1154G/A (rs1570360), -634C/G (rs2010963), and +936C/T (rs3025039) polymorphisms may not be responsible for OA susceptibility in the Thai population. However, the OA patients with A/A genotype at the -2578C/A seemed to have a lower potential risk of developing severe OA than those with the C/A and C/C genotypes. These findings would help elucidate and facilitate a better understanding of the genetic fundamentals of OA.

Does the intramedullary femoral canal plug reduce blood loss during total knee arthroplasty?

INTRODUCTION: The benefit of the femoral canal bone plug during total knee arthroplasty (TKA) in reducing blood loss has never been proven. The aim of this meta-analysis was to determine whether the femoral canal bone plug significantly reduces blood loss in primary TKA. METHOD: All studies published before December 2021 were searched. The inclusion criteria were randomized controlled trials comparing blood loss between TKA with plugged and unplugged femoral intramedullary canal, respectively. The primary outcome was postoperative hemoglobin reduction. RESULTS: Five studies with a total of 717 patients (361 in the plugged group, 356 in the unplugged group) met the criteria for inclusion in the meta-analysis. The mean difference in hemoglobin level between the two groups was 0.92 g/dL, with significantly less hemoglobin reduction in the plugged group (95% confidence interval [CI] - 1.64 to - 0.21, p = 0.01). The patients in the plugged group also had a significantly lower risk of receiving a blood transfusion (risk ratio 0.58, 95% CI 0.47-0.73, p < 0.00001). CONCLUSIONS: This meta-analysis demonstrates that using a femoral canal bone plug can significantly reduce blood loss and lower the risk ratio of blood transfusion in patients undergoing TKA.

Cytokine Profiling and Intra-Articular Injection of Autologous Platelet-Rich Plasma in Knee Osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease leading to joint pain and stiffness. Due to lack of effective treatments, physical and psychological disabilities caused by OA have a detrimental impact on the patient's quality of life. Emerging evidence suggests that intra-articular injection of platelet-rich plasma (PRP) may provide favorable results since PRP comprises not only a high level of platelets but also a huge amount of cytokines, chemokines, and growth factors. However, the precise mechanism and standardization method remain uncertain. This study aimed to examine cytokine profiling in both PRP and platelet-poor plasma (PPP) of knee OA patients and to determine the effects of PRP on OA chondrocytes and knee OA patients. PRP contained a wide variety of cytokines, chemokines, growth factors, and autologous intra-articular PRP injection resulted in favorable outcomes in knee OA patients. Significant increases in levels of IL-1, IL-2, IL-7, IL-8, IL-9, IL-12, TNF-α, IL-17, PDGF-BB, bFGF, and MIP-1ß were detected in PRP compared to PPP (p < 0.001). An in vitro study showed a marked increase in proliferation in OA chondrocytes cultured with PRP, compared to PPP and fetal bovine serum (p < 0.001). In a clinical study, knee OA patients treated with PRP showed improvement of physical function and pain, assessed by physical performance, Western Ontario and McMaster Universities Arthritis Index and visual analog scale. Our findings from both in vitro and clinical studies suggest that intra-articular PRP injection in knee OA patients may be a potential therapeutic strategy for alleviating knee pain and delaying the need for surgery.

Upregulation of antigen presentation function and inflammation in chondrocytes by induction of proteoglycan aggrecan peptides (P16-31 and P263-280).

OBJECTIVES: A central hallmark of osteoarthritis (OA) is cartilage destruction. Chondrocytes not only control cartilage metabolism, but are capable of immunogenic responses. The role of chondrocytes in the pathogenesis of OA is still unclear. In this study, we aimed to determine the immunological role of chondrocytes in response to proteoglycan aggrecan (PG) peptides. METHODS: Human chondrocytes were isolated from cartilage of knee OA patients undergoing knee arthroplasty and stimulated with proteoglycan aggrecan peptides in the presence of IFNγ. Antigen presentation markers, co-stimulatory molecules, cytokine production, gene expression and antigen presentation to T cells were evaluated. RESULTS: Our results show that IFNγ was required for the expression of MHC class I and II. However, stimulation with PG peptides P16-31 and P263-280, but not P2379-2394, increased expression level of co-stimulatory molecules (CD80 and CD86) and IL-6, IL-8 and TNFα production. This upregulation was seen in chondrocytes to nearly comparable levels of professional antigen-presenting cells. A similar pattern of gene expression was observed between P16-31 and P263-280 peptide stimulation on chondrocytes and this was different from P2379-2394 peptide treatment. Co-culture with autologous T cells revealed signi cant proliferation of cells when stimulating with the P263-280 peptides. CONCLUSIONS: Our study shows that human chondrocytes display unique features of antigen presentation. Their ability to process certain proteoglycan aggrecan peptides, in which these molecules are synthesised by the cartilage themselves render the possibility of a role for "self-antigens" in the immunopathogenesis of OA.

Two or four injections of platelet-rich plasma for osteoarthritic knee did not change synovial biomarkers but similarly improved clinical outcomes.

We compared two and four intra-articular injections of platelet-rich plasma (PRP) in terms of changes of synovial cytokines and clinical outcomes. One hundred twenty-five patients having knee osteoarthritis (OA) underwent PRP injections at a 6-week interval. Before each PRP injection, synovial fluid aspiration was collected for investigation. Patients were divided into two or four intra-articular PRP injections (group A and B, respectively). Changes in synovial biomarkers were compared with the baseline levels of both groups, and clinical outcomes were evaluated until one year. Ninety-four patients who had completed synovial fluid collection were included for final evaluation, 51 in group A and 43 in group B. There were no differences in mean age, gender, body mass index (BMI), and radiographic OA grading. The average platelet count and white blood cell count in PRP were 430,000/µL and 200/ µL, respectively. There were no changes of synovial inflammatory cytokines (IL-1ß, IL-6, IA-17A, and TNF-alpha), anti-inflammatory cytokines (IL-4, IL-10, IL-13, and IL-1RA), and growth factors (TGF-B1, VEGF, PDGF-AA, and PDGF-BB) between baseline levels and six weeks in group A, and 18 weeks in group B. Both groups had significantly improved clinical outcomes from six weeks including visual analog scale (VAS), patient-reported outcome measures [PROMs; Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index and Short Form-12 (SF-12)], with a significant delayed improvement of performance-based measures [PBMs; time up and go (TUG), 5-time sit to stand test (5 × SST), and 3-min walk test (3-min WT)]. In conclusion, two- or four-PRP intra-articular injection at a 6-week interval for knee OA demonstrated no changes of synovial cytokines and growth factors but similarly improved clinical outcomes from 6 weeks until 1 year.

Effect of ultrasound-guided selective sensory nerve blockade of the knee on pain management compared with periarticular injection for patients undergoing total knee arthroplasty: A prospective randomized controlled trial.

BACKGROUND: Ultrasound-guided selective sensory nerve blockade (SSNB) of the knee, including an adductor canal block (ACB), anterior femoral cutaneous nerve block, and infiltration between the popliteal artery and posterior capsule of the knee may provide effective motor-sparing knee analgesia for total knee arthroplasty (TKA). We hypothesized that the SSNB would manage pain better on ambulation 24 hours postoperatively compared to periarticular infiltration (PAI), when combined with postoperative continuous ACB. METHODS: Seventy-two patients undergoing elective TKA under spinal anesthesia were randomly assigned to either SSNB (SSNB group) or intraoperative PAI (PAI group). All patients received postoperative multimodal analgesia, including continuous ACB. The primary outcome was pain on ambulation 24 hours postoperatively. Secondary outcomes included rest and dynamic numerical rating scale pain score, intravenous morphine requirement, functional performance measures, adverse events, satisfaction, and length of stay. RESULTS: There was no difference in pain score during movement between the groups (mean difference -0.48 [-1.38 to 0.42], p = 0.3) and other immediate overall pain scores 24 hours postoperatively. Patients in the SSNB group had significantly lower intravenous morphine requirement than the PAI group for 48 hours postoperatively (0 [0, 0] vs. 0 [0, 2]; p = 0.008). There was no intergroup difference in the performance-based measures, satisfaction, and length of stay. CONCLUSIONS: The SSNB did not provide superior postoperative analgesia, or improvement in immediate functional performance. However, it may result in lower opioid consumption postoperatively when compared with the intraoperative PAI.

The analgesic efficacy of anterior femoral cutaneous nerve block in combination with femoral triangle block in total knee arthroplasty: a randomized controlled trial.

BACKGROUND: Ultrasound-guided femoral triangle block (FTB) can provide motor-sparing anterior knee analgesia. However, it may not completely anesthetize the anterior femoral cutaneous nerve (AFCN). We hypothesized that an AFCN block (AFCNB) in combination with an FTB would decrease pain during movement in the immediate 12 h postoperative period compared with an FTB alone. METHODS: Eighty patients scheduled to undergo total knee arthroplasty were randomized to receive either FTB alone (FTB group) or AFCNB with FTB (AFCNB + FTB group) as part of the multimodal analgesic regimen. The primary outcome was pain during movement at 12 h postoperatively. Secondary outcomes included numeric rating scale (NRS) pain scores, incidence of surgical incision site pain, intravenous morphine consumption, immediate functional performance, patient satisfaction, and length of hospital stay. RESULTS: The NRS pain scores on movement 12 h postoperatively were significantly lower in the AFCNB + FTB group than in the FTB group (mean difference: -2.02, 95% CI: -3.14, -0.89, P < 0.001). The incidence of pain at the surgical incision site at 24 h postoperatively and morphine consumption within 48 h postoperatively were significantly lower (P < 0.001), and quadriceps muscle strength at 0° immediately after surgery was significantly greater in the AFCNB + FTB group (P = 0.04). CONCLUSIONS: The addition of ultrasound-guided AFCNB to FTB provided more effective analgesia and decreased opioid requirement compared to FTB alone after total knee arthroplasty and may enhance immediate functional performance on the day of surgery.

The infrapatellar fat pad produces interleukin-6-secreting T cells in response to a proteoglycan aggrecan peptide and provides dominant soluble mediators different from that present in synovial fluid.

OBJECTIVE: The purpose of this study was to investigate the effects of osteoarthritis (OA) peripheral blood mononuclear cell (PBMC) -stimulating proteoglycan aggrecan peptides on T cells present in infrapatellar fat pads (IPFPs) and synovial tissues, and to correlate these findings with mediators present in synovial fluid of OA patients. METHODS: We tested for interleukin-6 (IL-6) -producing T cells in IPFPs of patients with knee OA using ELISPOT. Cytokine and cytotoxic mediator production from OA PBMCs, IPFPs, synovial tissues, and synovial fluids in response to proteoglycan aggrecan peptides were quantified by cytometric bead array. Patterns of cytokine and cytotoxic mediator production were analyzed and compared. RESULTS: T cells from IPFPs elicited strong responses towards the p263-280 peptide by secreting IL-6. In addition, there was a trend that the p263-280 peptide stimulated higher production of cytokines/cytotoxic mediators than other proteoglycan aggrecan peptides, although this was not statistically significant. In patients with knee OA, a group of cytotoxic mediators (sFas, perforin, granzyme A, and granulysin) and IL-6 were detectable at high levels from the synovial fluid. In addition, inflammation in patients with knee OA was more pronounced in joint-surrounding tissues than levels in circulating peripheral blood. CONCLUSION: Our data suggest that T cells responding to the p263-280 peptide contribute to the secretion of various soluble mediators that are found within the synovial fluid. We also identified potential new candidates that may serve as biomarkers of knee OA.