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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.

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.

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.

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-1β 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.

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 OA underwent leukocyte-poor PRP with 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 cytokines and growth factors 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, BMI, and OA grading. The average platelet count in PRP was 430,000/µL. 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 measure (PROM; WOMAC and SF-12), with a significant delayed improvement of performance-based measure [PBM; time up and go (TUG), 5-time sit to stand test (5×SST), and 3-minute walk test (3-min WT)]. In conclusion, two- or four-PRP 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 one year.

Osteoarthritis (OA) is a degenerative articular disorder manifested by cartilage destruction, subchondral sclerosis, osteophytes, and synovitis, resulting in chronic joint pain and physical disability in the elderly. The purpose of this study was to investigate mitochondrial DNA copy number (mtDNA(CN)) and inflammatory cytokines in primary knee OA patients and healthy volunteers. A total of 204 knee OA patients and 169 age-matched healthy volunteers were recruited. Their relative blood leukocyte mtDNA(CN) was assessed by quantitative real-time polymerase chain reaction (qRT-PCR), and ten inflammatory cytokines in their plasma were detected by multiplex immunoassay. Blood leukocyte mtDNA(CN) in the OA group was significantly lower than that in the control group. Leukocyte mtDNA(CN) in the control group was negatively correlated with their age (r=−0.380, P

Objective Glypican-3 possesses a possible action in regulation of bone growth and development implicated in osteoarthritis (OA) pathology. Therefore, this study aimed to investigate glypican-3 in plasma and synovial fluid of knee OA patients and to determine the possible association between glypican-3 levels and radiographic severity. Design A total of 80 knee OA patients and 80 healthy controls were recruited. Glypican-3 levels in plasma and synovial fluid were measured using enzyme-linked immunosorbent assay. The severity of knee OA was assessed by radiographic grading according to the Kellgren-Lawrence classification. Relative mRNA expression of glypican-3 in 10 inflamed synovial tissues from OA patients and 10 noninflamed synovial controls was quantified using real-time polymerase chain reaction. Results Plasma glypican-3 levels were significantly lower in OA patients than in healthy controls ( P = 0.03), whereas synovial fluid glypican-3 levels were remarkably greater than in paired plasma samples of OA patients ( P < 0.001). Subsequent analysis demonstrated that plasma and synovial fluid glypican-3 levels were inversely associated with the radiographic severity of knee OA ( r = −0.691, P < 0.001; r = −0.646, P < 0.001, respectively). Furthermore, there was a positive relationship between plasma and synovial fluid glypican-3 levels in knee OA patients ( r = 0.515, P < 0.001). Additionally, overexpression of glypican-3 mRNA was observed in inflamed synovium of OA patients ( P = 0.021). Conclusions The present study revealed that plasma and synovial glypican-3 levels were negatively associated with radiographic severity of knee OA. Glypican-3 could emerge as a potential biomarker for reflecting the severity of knee OA and might play a plausible role in the pathophysiology of degenerative joint disease.

Background This study aimed to determine the optimal location of local anesthetic injection in the interspace between the popliteal artery and posterior capsule of the knee (iPACK), using the anatomical pattern of the articular branch of tibial nerve (ABTN). We hypothesized that injection at the level of ABTN forming a popliteal plexus would mainly spread throughout the popliteal fossa without contacting the tibial or peroneal nerves. Methods The anatomical study included 30 soft cadavers. Ultrasound-guided dye injection was performed in legs of 10 cadavers after identifying the position of the ABTN and surrounding structures, followed by dissection to assess its spread. Clinical study was conducted in 15 patients undergoing total knee arthroplasty (TKA) with ultrasound-guided injection in the iPACK. All patients also received continuous adductor canal block. Sensorimotor function of the tibial and common peroneal nerves was determined. Results In the distal portion of the popliteal fossa, the tibial nerve and popliteal vessels ran superficially and closely together. The trajectory of ABTN ran lateral to the popliteal vasculature, forming a plexus towards the posterior capsule of the knee below the medial side of the upper edge of lateral femoral condyle. In cadavers, the ABTN and surrounding area of the popliteal plexus were stained with dye after injection. In the clinical study, no patients experienced complete motor or sensory blocks. Conclusions We described a modified iPACK technique injection at the level of the ABTN forming the popliteal plexus, and it may constitute an optional anesthetic regimen to promote early ambulation following TKA.

Background Peripheral nerve block and local infiltration analgesia (LIA) have an increasing role as part of multimodal analgesia for enhanced recovery after total knee arthroplasty (TKA). We hypothesized that the combination of obturator nerve block (ONB) and tibial nerve block (TNB) would reduce pain and opioid consumption more than ONB or TNB alone when combined with continuous adductor canal block and LIA. Methods Ninety patients were recruited into the study and received spinal anesthesia, LIA, and continuous adductor canal block. They were further randomized to receive either an ONB (group 1), a TNB (group 2), or both (group 3). The primary outcome was total morphine consumption over the postoperative 24 hours. The secondary outcomes included visual analog scale scores, time to first and total dosage of rescue analgesia, Timed Up and Go test, range of motion, muscle strength test, hospital stay, and patient satisfaction. Results Eighty-nine patients completed analysis. The median total morphine consumption during the first 24 postoperative hours was 2 mg (interquartile range [IQR] 0-4) in group 3, 4 mg (IQR 2-8) in group 2, and 6 mg (IQR 6-14) in group 1 (P Conclusion The combination of triple nerve block was superior to double nerve block in improving analgesia and functional outcomes in the immediate postoperative period after total knee arthroplasty, when combined with LIA.

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 a FTB would decrease pain during movement in the immediate 12-hour postoperative compared with a FTB alone. Methods Eighty patients scheduled to undergo total knee arthroplasty (TKA) were randomized to receive either FTB alone (FTB group) or AFCNB with FTB (AFCNB + FTB group) as a part of the multimodal analgesic regimen. The primary outcome was pain during movement 12 hours 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 hours postoperatively were significantly lower in patients of AFCNB + FTB group compared to those in patients of FTB group (mean difference, -2.02 [95% confidence interval: -3.14, -0.89], P < 0.001). Incidence of pain at the site of surgical incision in 24 hours postoperatively and morphine consumption in 48 hours postoperatively were significantly lower (P < 0.001) and quadriceps muscle strength at 0 degree immediately after the surgery was significantly greater in patients of 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 TKA and may enhance immediate functional performance on the day of surgery.

Background Since 2014, the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) algorithm for the management of knee osteoarthritis (OA) is available worldwide. Aim Based on this document, a Southeast Asia Working Group (SEAWG) wished to see how the new ESCEO algorithm developed in 2019 was perceived by Southeast Asian experts and how it was integrated into their clinical practice. Methods A SEAWG was set up between members of the international ESCEO task force and a group of Southeast Asian experts. Results Non-pharmacological management should always be combined with pharmacological management. In step 1, symptomatic slow-acting drugs for osteoarthritis are the main background therapy, for which high-quality evidence is available only for the formulations of patented crystalline glucosamine sulfate and chondroitin sulfate. In step 2, oral NSAIDs are a useful option, considering the cardiovascular/renal/gastrointestinal profiles of the individual patient. Intra-articular hyaluronic acid and corticosteroids are a possible alternative to oral NSAIDs, but limited evidence is available. If steps 1 and 2 do not give adequate relief of symptoms, tramadol can be used, but its safety is debated. In general, the indications of the ESCEO algorithm are important in Southeast Asian countries, but the reimbursement criteria of local health systems are an important aspect for adherence to the ESCEO algorithm. Conclusion This guidance provides evidence-based and easy-to-follow advice on how to establish a treatment algorithm in knee OA, for practical implementation in clinical practice in Southeast Asian countries.

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.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.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.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.

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.

Telomere length is a hallmark characteristic of ageing and age-related diseases. Osteoarthritis (OA) is the most common cause of joint pain and physical disability in the elderly. Previous studies have revealed the role of telomere shortening in OA; however, the relationship between telomere length, muscle strength and physical performance in knee OA patients remains unknown. The aim of the present study was to investigate the association of telomere length and physical performance in patients with knee OA. A total of 202 patients with knee OA and 60 healthy controls were enrolled in the study. The quality of life was assessed using Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and Short Form Health Survey. The skeletal muscle mass was examined using bioelectrical impedance analysis, while the muscle strength was analyzed using hand grip force and isometric knee extension force. The physical performance of patients with knee OA was also investigated using gait speed, Timed up and go test (TUGT), Sit to stand test and 6-min walk test (6MWT). Blood leukocyte relative telomere length (RTL) was assessed using real time quantitative PCR. The mean blood leukocyte RTL in knee OA subjects was significantly lower compared with healthy controls (P

Obesity is a major contributor to deterioration of physical function toward sarcopenia in knee osteoarthritis (OA) due to its effect mediated through adipokines-derived molecules that have pro-/anti-inflammatory properties. This study aimed to investigate relationships of serum adiponectin, 25-hydroxyvitamin D (25(OH)D), interleukin (IL)-6, and physical performance in knee OA patients. A total of 175 knee OA patients and 52 healthy controls were recruited. Serum adiponectin, 25(OH)D, IL-6, biochemical markers, knee pain and functional scores, muscle strength, physical performance, metabolic parameters, and body composition were evaluated. Serum adiponectin levels were significantly higher in knee OA patients than that in controls, while its serum levels were significantly decreased in obese patients, especially those with sarcopenia. Furthermore, there were independent relationships of serum adiponectin with body composition parameters, knee pain scores, physical function tests, and metabolic parameters in knee OA patients. Besides, serum adiponectin levels were positively associated with 25(OH)D levels, and negatively correlated with C-reactive protein and IL-6 levels in knee OA. Additionally, low serum adiponectin could be used to distinguish knee OA patients with sarcopenic obesity from those without sarcopenic obesity. Circulating adiponectin levels may serve as a possible surrogate biomarker for exacerbated physical function in knee OA patients-particularly sarcopenic obesity.

BackgroundA combination of motor-sparing analgesia with local infiltration analgesia (LIA) and continuous adductor canal block (CACB) may improve postoperative pain and functional recovery for total knee arthroplasty (TKA). We hypothesized that the addition of a novel technique for posterior knee block, known as the infiltration between the popliteal artery and capsule of the knee (iPACK) block, to LIA with CACB would reduce opioid requirements.MethodsIn this double-blinded randomized controlled trial, 72 patients were assigned to receive either LIA with CACB (LIA+CACB group) or iPACK block with LIA and CACB (iPACK+LIA+CACB group). The primary outcome was cumulative postoperative intravenous morphine consumption within 24 hours. The secondary outcomes included numerical rating scale pain scores, incidence of posterior knee pain, performance test results, patient satisfaction, length of stay, and adverse events.ResultsMorphine consumption within 24 hours postoperatively showed no significant intergroup difference (LIA+CACB; 1.31±1.85 mg vs iPACK+LIA+CACB; 0.61±1.25 mg, p=0.08). There were no clinically significant differences in the overall pain scores between the groups. The lower Timed Up and Go test scores on postoperative days 1 and 2, along with a shorter duration of hospitalization, were found in the iPACK+LIA+CACB group (pConclusionThe addition of an iPACK block to the LIA and CACB does not reduce the postoperative opioid consumption nor improve analgesia. However, it may improve immediate functional performance and reduce the length of hospitalization after TKA.Trial registration numberTCTR20180702001.

Objective.Osteoarthritis (OA) is a condition that features inflammation and immune responses of innate and adaptive immunity. The role of T cells in knee OA pathogenesis is still unclear. Our aim was to characterize T cell functions and their clonality in patients with knee OA in peripheral blood (PB) and infrapatellar fat pads (IPFP).Methods.We isolated T cells from PB and IPFP of patients with knee OA and PB of healthy individuals and determined soluble mediators produced from these cells. In addition, we performed a clonal analysis of activated CD8+ T cells and compared the T cell receptor β-variable gene chain (TRBV) usages between T cells in PB and IPFP of patients with knee OA.Results.Our results suggest that in patients with knee OA, circulating T cells possess a more “cytotoxic” profile or rather impaired cytokine production, but the knee microenvironment allows for these T cells to produce proinflammatory cytokines [interleukin (IL)-1β, IL-6, tumor necrosis factor], IL-17, and interferon-γ within IPFP. Activated CD8+ IPFP T cells carry different repertoire distribution from those present in PB of patients with knee OA. Shared TRBV usage of activated CD8+ IPFP T cells among the 3 patients with knee OA was also observed.Conclusion.Our study describes the nature of T cells in knee OA that may be due to “unhealthy” aging or other factors that drive healthy aging T cells into a state of imbalance, thus contributing to the pathogenesis of knee OA.

Ti-based amorphous alloys containing no harmful elements are desired. However, many Ti-based amorphous alloys contain toxic elements such as Al, Ni, V and Be. The presence of toxic elements within amorphous alloys is a concern when they are intended for use as a biomaterial. This problem has steered many researchers toward the development of Ti-based amorphous alloys without toxic elements. Our novel amorphous alloys were developed based on this principle. A series of Ti44Zr10Pd10Cu6+xCo23-xTa7 (x = 0, 4, 8) amorphous alloys were developed for biomedical application. A series of protocol tests were performed to check for biocompatibility and potential use of the novel alloys in humans. First, alloy ingots were alloyed by induction melting and then cast into copper molds. The cast rod was then used as the plasma cathode in a filtered cathodic vacuum arc deposition chamber to coat the 25-nm amorphous alloy thin film on the cover glass slides. These coated cover glass slides were then examined for biocompatibility. Cell proliferation and cell differentiation were investigated using Methylthiazol Tetrazolium assay test and by alkaline phosphatase assay on osteoblast like cells (SaOS-2), respectively. Field emission scanning electron microscopy was performed to evaluate the thin film surface characteristics. The thickness of thin film was analyzed using a Stylus profilometer. An adhesion scratch test was administered to evaluate the thin film adhesive strength and indirect hardness comparison. Electron Dispersive X-ray Spectrometry was performed to study the elemental composition. Lastly, a medical grade Ti-6Al-4V alloy was studied in parallel as a control material. Results indicated that all investigated Ti-based amorphous alloys were non-cytotoxic and were comparable to the Ti-6AL-4V. They also demonstrated an ability to support differentiation of osteoblast like cells. The adhesion and the hardness of the thin films on the substrates were superior to that of Ti-6Al-4V. The results suggested that the novel alloys in this study could be potentially utilized in biomedical applications.

Introduction: Total knee arthroplasty (TKA) is associated with intense postoperative pain for which effective analgesia is essential to facilitate early postoperative recovery. Adductor canal block (ACB) and local infiltration analgesia (LIA) have become increasingly involved in postoperative pain management after TKA. We aimed to compare their efficacy and outcomes in patients undergoing TKA. Materials and Methods: Sixty patients undergoing unilateral TKA were randomized to receive either postoperative single-injection ACB (Group A) or LIA (Group L) during the operation. All patients received spinal anaesthesia. Primary outcome was total morphine consumption over postoperative 24 hours. Visual analog pain scale, time to first and total dosage of rescue analgesia, performance-based evaluations [timed-up and go (TUG) test, quadriceps strength], side-effects, length of hospital stay and patient satisfaction were measured. Results: Fifty-seven patients were available for analysis. Median total morphine consumption over 24 and 48 postoperative hours of Group A were significantly less than Group L (6/10 mg vs 13/25 mg, p, 0.008 and 0.001, respectively). Similarly, Group A had significantly lower VAS at postoperative 6, 12 and 18 hours, VAS at ambulation on postoperative (POD) 1-3, better TUG tests on POD 2 and during POD 3 than those of Group L. However, quadriceps strength and patient satisfaction were not different between both groups. Conclusion: Patients undergoing TKA with single-injection ACB required less postoperative opioids than those with LIA. Furthermore, multimodal analgesia using ACB provided better postoperative analgesia, as well as performance-based activities, than those with LIA.

Increasing numbers of hip and knee arthroplasty may associate with higher risk of complications such as venous thromboembolism. Most of Thai orthopedic surgeons ignore thromboprophylaxis because of less symptomatic VTE in Asian population. The Thai consensus on venous thromboembolism in hip and knee surgery consist of twenty-four common questions about VTE including their supported literatures. The gold standard of diagnosis is contrast venography although the duplex ultrasound has more role in postoperative patients. Thai patients undergoing hip and knee surgery seem to have lower prevalence of VTE than Caucasian. However, mechanical or chemoprophylaxis should be considered especially in the high risk group and hip fracture in elderly.

The associations between serum leptin, vitamin D status, sarcopenic obesity, muscle strength and physical performance in osteoarthritis (OA) remain uncertain.To analyse the relationships between serum leptin, vitamin D status, muscle strength and physical performance in OA patients.A total of 208 knee OA patients were enrolled. Serum leptin, vitamin D, muscle strength and physical performance were evaluated.OA patients with sarcopenic obesity had significantly higher serum leptin levels than those with non-sarcopenic obesity. In addition, knee OA patients with sarcopenic obesity displayed low grip strength and poor physical performance. Furthermore, high serum leptin was negatively associated with vitamin D and physical performance.Serum leptin levels were correlated with low vitamin D, reduced muscle strength and functional impairment, suggesting that serum leptin might serve as a biomarker reflecting physical performance in OA patients.

Aim The aims of this study were to compare leukocyte relative telomere length (RTL) in knee osteoarthritis (OA) patients and healthy controls and to investigate associations between plasma angiogenic cytokine concentrations and leukocyte RTL. Method Eighty knee OA patients and 60 age-matched controls were enrolled. Leukocyte RTL was assessed using real-time quantitative polymerase chain reaction (qPCR). Angiogenic cytokines were measured by a multiplex immunoassay. Results Leukocyte RTL in knee OA patients was significantly lower than that in healthy controls (1.1 ± 0.4 vs. 1.3 ± 0.6, P = 0.039). Plasma angiopoietin-2, follistatin, granulocyte-colony stimulating factor (G-CSF), hepatocyte growth factor (HGF), interleukin-8 (IL-8), platelet endothelial cell adhesion molecule-1 (PECAM-1), and vascular endothelial growth factor (VEGF) levels in knee OA patients were higher than those in controls (P < 0.01). Correlation analysis revealed significant negative correlations between leukocyte RTL and plasma levels of HGF (r = −0.377, P = 0.017), VEGF (r = −0.405, P = 0.009) and G-CSF (r = −0.347, P = 0.026). In contrast, plasma angiopoietin-2, follistatin, IL-8, leptin, platelet-derived growth factor-BB and PECAM-1 were not correlated with leukocyte RTL. Conclusion Telomere length was shortened in knee OA patients compared to healthy controls. Plasma HGF, VEGF and G-CSF were negatively correlated with leukocyte RTL, suggesting involvement of telomere shortening and these cytokines in knee OA.

Background and objectiveAn ultrasound-guided anesthetic technique targeting the interspace between the popliteal artery and capsule of the posterior knee (iPACK) can provide posterior knee analgesia with preserved motor function after total knee arthroplasty (TKA). This study compared the peroneal nerve motor-sparing effects of iPACK block and tibial nerve block (TNB) when combined with local infiltration analgesia (LIA) and continuous adductor canal block (CACB).MethodsIn this study, 105 patients scheduled for elective TKA were randomized to receive proximal iPACK block (iPACK1), distal iPACK block (iPACK2), or TNB, along with spinal anesthesia, modified LIA, and CACB. The primary outcome was the incidence of common peroneal nerve (CPN) motor blockade. Secondary outcomes included CPN sensory function, tibial sensorimotor function, posterior knee pain, pain score, intravenous morphine requirement, timed up-and-go test, quadriceps muscle strength, range of motion, length of hospital stay, patient satisfaction, and adverse events.ResultsThe incidence of CPN motor blockade was significantly higher in the TNB group than in the iPACK1 (p=0.001) and iPACK2 (p=0.001) groups, but was not significant between the iPACK1 and iPACK2 groups (p=0.76). Tibial nerve motor function was more preserved in the iPACK1 and iPACK2 groups than in the TNB group (pConclusionsCompared with TNB, iPACK1 and iPACK2 preserved CPN and tibial nerve motor function to a greater extent. However, iPACK2 did not demonstrate complete CPN and tibial nerve motor blockade while maintaining effective posterior knee pain relief.Trial registration numberTCTR20180206002.

Aim Joints inflammation is one of the most pathologic processes leading to the development of osteoarthritis (OA), possibly leading to genomic instability. LINE-1 is transposable elements, and alterations in LINE-1 methylation induced by 8-hydroxy-2′-deoxyguanosine (8-OHdG) can cause genomic instability contributing to OA development. Herein, the present study examined associations between LINE-1 methylation, 8-OHdG, and knee OA severity. Methods LINE-1 methylation levels were measured in 104 knee OA patients and 96 healthy controls by quantitative combined bisulfite restriction analysis. 8–OHdG was investigated by ELISA. The knee OA severity was appraised by questionnaires (VAS, WOMAC, KOOS, and lequesne index) and radiological severity based on the grading of Kellgren and Lawrence (KL) standard criteria. Key findings Blood leukocyte LINE-1 methylation levels were significantly lower in knee OA patients than in healthy controls. Interestingly, individuals with LINE-1 hypomethylation were significantly associated with an elevated risk of knee OA. Linear regression analysis revealed that LINE-1 methylation was independently associated with KL grading of knee OA. Furthermore, plasma 8–OHdG levels in OA cases were not significantly different from those in healthy volunteers, whereas synovial fluid 8–OHdG values were considerably higher than in paired plasma specimens of the OA subjects. Significance This study demonstrated that LINE-1 hypomethylation in blood leukocytes was associated with increased risk and radiographic severity of knee OA, and increased synovial fluid 8–OHdG levels were observed in knee OA patients. Collectively, LINE-1 hypomethylation and elevated 8–OHdG could emerge as biomarkers indicating the severity of knee OA and may take a possible part in the pathological process of knee OA.

Chulalongkorn Medical Bulletin, 1, 1, 013-026

Chulalongkorn Medical Journal, 63, 2, 067-071

The combination of adductor canal block (ACB) and infiltration between the popliteal artery and the posterior capsule of the knee (iPACK) block may provide sufficient motor-sparing anterior and posterior knee analgesia after total knee arthroplasty. This study aimed to determine if ACB with iPACK block was noninferior to ACB with periarticular injection (PAI) when combined with postoperative multimodal analgesia regimen.Seventy-six patients were randomized to receive either ACB + iPACK block and continuous ACB (CACB) (ACB + iPACK group) or PAI and CACB (ACB + PAI group). Noninferiority was concluded for the primary outcome if the adjusted mean between-group difference in pain on movement at 12 postoperative hours was within 1.3 points on a visual analog pain scale. Pain scores, morphine consumption, functional performance, and adverse events were the secondary outcome measures assessed for superiority.Adjusted mean differences, (ACB + iPACK) - (ACB + PAI), in anterior and posterior knee pain scores on movement at 12 postoperative hours were -0.66 (-1.86, 0.54) and -0.19 (-1.36, 0.99), respectively. The upper limit of 95% confident interval was lower than the prespecified noninferiority limit. The mean visual analog scale pain scores were low and no clinically significant differences between groups. However, morphine requirement at 48 postoperative hours was significantly higher (P.05) and showed greater reduced quadriceps strength at 0 and 45 degrees on postoperative day 0 (P = .006 and .04, respectively) in the ACB + iPACK group.ACB with iPACK block provides a noninferior analgesia compared with PAI when combined with CACB. However, patients who received ACB + iPACK block may require higher amounts of opioids and have worse immediate functional performance.Therapeutic level I.

Background Skin numbness after total knee arthroplasty (TKA) was reported in relation to injury of the infrapatellar branch of saphenous nerve (IPBSN). Methods Phase I study: A nonrandomized and nonconsecutive selection of 30 patients undergoing unilateral TKA, using minimally invasive surgery approach, and 30 patients having standard approach were included. Area of skin numbness was periodically evaluated and compared until 1-year follow-up (FU). Phase II study: we dissected 15 normal cadaveric knees and followed the course and distribution of IPBSN. Results Twenty-nine predominantly female patients in each group completed 1-year FU with no differences in demographic data. Both the groups had significantly improved Knee Society Score clinical and function scores with no statistical differences. The numb areas in both the groups similarly decreased from 2 weeks (51.7 cm 2 vs 51.1 cm 2 ) to 1 year (2.1 cm 2 vs 2.4 cm 2 ) with similar percentages of no skin numbness at 1 year (69% vs 65%). The IPBSN branched from saphenous nerve before exiting the adductor canal and ran longitudinally and obliquely. It was found as a single nerve in 20%, a 2-branch nerve in 67% and a 3-branch nerve in 13%. All branches crossed the knee midline between superior patellar pole and tibial tubercle. Conclusion Clinical study showed that TKA using minimally invasive surgery approach provided similar area of skin numbness to standard approach. Numbness area gradually decreased at serial FUs in both the groups. The cadaveric study demonstrated that the IPBSN consistently gave no branch passing the knee midline above superior patellar pole.

Objective: The objective of this study is to compare inflammatory cytokine levels in primary knee osteoarthritis (OA) patients and healthy controls.Methods: A total of 32 knee OA patients and 14 healthy controls were enrolled. A multiplex immunoassay was utilized for 10 cytokines in plasma and synovial fluid.Results: Plasma IL-2, IL-4, and IL-6 concentrations were significantly greater in knee OA patients than controls. Moreover, both plasma IL-4 and IL-6 were positively correlated with the radiographic severity of knee OA.Conclusions: Plasma IL-4 and IL-6 may serve as biomarkers reflecting the severity of OA.