The role of inflammation and pain in osteoarthritis (OA) is not fully understood. We evaluated the association between pro-inflammatory biomarkers and pain. We used baseline data and samples from a randomized controlled trial of colchicine for symptomatic knee OA. Severity of pain of the more symptomatic knee was assessed by National Health and Nutrition Examination Survey-I (NHANES-I) criterion and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain index. Pains on movement and at rest were self-reported on an 11-point Likert scale. Severity of radiographic tibiofemoral OA was assessed by Kellgren and Lawrence (KL) grade. Concentrations of synovial fluid (sf) IL-1β, IL-6, IL-8, TNFα, C-terminal telopeptides of Type I collagen (CTXI) and C-telopeptide of Type II collagen (CTXII), as well as urinary (u) CTXII were measured. Of the 109 patients enrolled in the study, 70 patients (70% women) with synovial fluid obtained by direct aspiration were included for analysis. The mean ± SD age and body mass index (BMI) of the patients were 57.6 ± 8.3 years and 28.8 ± 5.2 kg/m2. After adjustment for age, sex, and BMI, sf IL-6 and IL-8 were statistically significantly associated with 11-point pain on movement, but not with pain at rest. No significant associations were observed with WOMAC pain scores. sf IL-1β (analyzed as detectable/non-detectable) was inversely associated with pain. In contrast, after adjustment, Sf TNFα was associated with WOMAC total pain and both pain on movement and at rest. sf/u CTXII was associated with radiographic severity, but not with knee pain. This study provides indication that OA pain mechanisms may differ according to the characteristics of the pain.

Uric acid may activate an innate immune response in osteoarthritis (OA), contributing to disease pathology and progression. We evaluated the effectiveness of colchicine on pain and function in symptomatic knee OA (KOA) and the underlying mechanism of action. Colchicine effectiveness in symptoms and inflammation modification in knee osteoarthritis (COLKOA) was a double-blind, placebo-controlled, randomized trial comparing 16 weeks of treatment with 0.5 mg twice-daily oral colchicine to placebo for knee osteoarthritis (KOA). The primary endpoint was ≥30% improvement in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at week 16. Secondary endpoints included improvement in pain (0-10 Likert scales); WOMAC pain; patient global assessment (0-100); physical function; the OARSI-OMERACT response; quality of life; and change in serum, urine, synovial fluid (SF) biomarkers of cartilage metabolism and inflammation, and plasma/SF colchicine concentrations. Of 109 randomly assigned participants, 39% (95% confidence interval (CI) 27-52%) and 49% (95% CI 36-62%) in the colchicine and placebo arms respectively met the primary endpoint at study end (P = 0.284, odds ratio 0.66, 95% CI 0.31-1.41). No strong evidence of treatment differences was identified on clinical secondary endpoints. Treatment significantly reduced mean serum hs-CRP (P = 0.008) and SF CTXI (P = 0.002); treatment tended to reduce inflammatory markers (SF IL-6, IL8, TNFα, CD14 and IL-18), but these differences were not statistically significant. Colchicine (0.5 mg twice-daily orally) reduced inflammation and high bone turnover biomarkers known to be associated with OA severity and progression risk, but did not reduce KOA symptoms over a 16-week study period. A longer-term study to evaluate for slow-acting disease modifying effects is warranted. The trial has been registered at clinicaltrials.gov as NCT02176460. Date of registration: June 26, 2014.

Background: Sarcopenia has been recognized as a determining factor in surgical outcomes and is associated with an increased risk of postoperative complications and readmission. Diagnosis is currently based on clinical guidelines, which includes assessment of skeletal muscle mass but not quality. Ultrasound has been proposed as a useful point-of-care diagnostic tool to assess muscle quality, but no validated cut-offs for sarcopenia have been reported. Using novel automated artificial intelligence (AI) software to interpret ultrasound images may assist in mitigating the operator-dependent nature of the modality. Our study aims to evaluate the fidelity of AI-aided ultrasound as a reliable and reproducible modality to assess muscle quality and diagnose sarcopenia in surgical patients. Methods: Thirty-six adult participants from an outpatient clinic were recruited for this prospective cohort study. Sarcopenia was diagnosed according to Asian Working Group for Sarcopenia (AWGS) 2019 guidelines. Ultrasonography of the rectus femoris muscle was performed, and images were analyzed by an AI software (MuscleSound® (Version 5.69.0)) to derive muscle parameters including intramuscular adipose tissue (IMAT) as a proxy of muscle quality. A receiver operative characteristic (ROC) curve was used to assess the predictive capability of IMAT and its derivatives, with area under the curve (AUC) as a measure of overall diagnostic accuracy. To evaluate consistency between ultrasound users of different experience, intra- and inter-rater reliability of muscle ultrasound parameters was analyzed in a separate cohort using intraclass correlation coefficients (ICC) and Bland–Altman plots. Results: The median age was 69.5 years (range: 26–87), and the prevalence of sarcopenia in the cohort was 30.6%. The ROC curve plotted with IMAT index (IMAT% divided by muscle area) yielded an AUC of 0.727 (95% CI: 0.551–0.904). An optimal cut-off point of 4.827%/cm² for IMAT index was determined with a Youden’s Index of 0.498. We also demonstrated that IMAT index has excellent intra-rater reliability (ICC = 0.938, CI: 0.905–0.961) and good inter-rater reliability (ICC = 0.776, CI: 0.627–0.866). In Bland–Altman plots, the limits of agreement were from −1.489 to 1.566 and −2.107 to 4.562, respectively. Discussion: IMAT index obtained via ultrasound has the potential to act as a point-of-care evaluation for sarcopenia screening and diagnosis, with good intra- and inter-rater reliability. The proposed IMAT index cut-off maximizes sensitivity for case finding, supporting its use as an easily implementable point-of-care test in the community for sarcopenia screening. Further research incorporating other ultrasound parameters of muscle quality may provide the basis for a more robust diagnostic tool to help predict surgical risk and outcomes.

Pain sensitization could be a risk factor for poor outcomes after knee replacement surgery (KR) for knee osteoarthritis (KOA). We aimed to evaluate the association between pre-operative central and peripheral pain sensitization measured using a digital pressure algometer and KR outcomes. Consecutive patients with severe KOA listed for KR were recruited. Sociodemographic and symptoms data were collected prior to surgery. Pre-operative pressure pain thresholds (PPTs) were measured using a digital pressure algometer at the index knee and forearm. Patient satisfaction at 6 and 12 months after KR was assessed using a 4-point Likert scale, and dichotomized to satisfied and dissatisfied to KR. Western Ontario and McMaster Universities Index (WOMAC) Pain and function was assessed. The associations between pre-operative PPTs with KR outcomes at 6 and 12 months were evaluated. Of the 243 patients recruited, response rate at 6 and 12 months were 95.5% and 96.7%. The dissatisfaction rates were 8.2% and 5.1% at 6 and 12 months. There was no statistically significant association between pre-operative index knee or forearm PPTs and patient satisfaction. PPTs measured at the knee, but not the forearm, were weakly associated with change in the WOMAC pain score at 12 months, after adjustment for confounding factors. Pre-operative central sensitization, measured by handheld digital algometry, was not statistically significantly associated with satisfaction or change in pain after KR. Pre-operative peripheral sensitization was associated with change in pain symptoms after KR; however, this association was weak and unlikely to be a meaningful predictor of KR outcome in clinical practice.

We aimed to evaluate the association between the adipokines: Leptin, Adiponectin, Resistin, and high sensitive-C-reactive protein (hs-CRP) with clinical, radiographical and magnetic resonance imaging (MRI) assessment of knee osteoarthritis (OA) severity. We performed a cross-sectional study in participants with earlier knee OA. Demographics, clinical (WOMAC), radiographical and MRI (BLOKS scoring) severity of knee OA were assessed. Serum leptin, adiponectin, resistin and hs-CRP were measured. Association of adipokines and hs-CRP with clinical, radiographic and MRI severity outcomes were evaluated using regression models with adjustment with age, sex, and body mass index (BMI). 137 participants with earlier knee OA (82% women, mean ​± ​SD age: 55.5 ​± ​7.8 years) were included. Participants had moderate knee OA symptoms, mean WOMAC pain and function were 30.6 ​± ​18.0, and 31.7 ​± ​19.8 respectively. Mean BMI was 27.0 ​± ​5.9 ​kg/m². After adjustment with age, sex and BMI, serum leptin was positively associated with osteophyte size, cartilage integrity, infrapatellar synovitis and effusion. While hs-CRP was associated with meniscus extrusion and adiponectin was associated with WOMAC pain and function. Serum adipokines, particularly leptin was associated with severity of various structural defects of the knee joint on MRI beyond age, sex and BMI in earlier knee OA.

Radiographs are currently accepted as the first‐line modality for the investigation of scaphoid fractures. Early use of magnetic resonance imaging (MRI) in patients with radio‐occult scaphoid fractures has been shown to be beneficial in the management of such patients. Incorporation of early MRI into the management protocol for scaphoid fracture is recommended.