Search

Objective: To describe the temporal patterns of knee pain in a community-based cohort over 12 years. Methods: Data on self-reported knee pain at 4 time points over 12 years were analyzed in participants from the Chingford Women's Study of osteoarthritis (OA) and osteoporosis. Pain status was defined as any pain in the preceding month and pain on most days in the preceding month. This status was used to classify participants according to pain patterns of asymptomatic, persistent, incident, or intermittent pain. Multinomial logistic regression was used to identify baseline predictors for each pain pattern. Results: Among the 489 women with complete followup data, the median age at baseline was 52 years (interquartile range [IQR] 48-58 years), the median body mass index (BMI) was 24.39 kg/m(2) (IQR 22.46-27.20), and 11.7% of the women had a Kellgren/Lawrence radiographic OA severity grade of ?2 in at least one knee. Among subjects reporting any pain in the preceding month versus those reporting pain on most days in the preceding month, 9% versus 2% had persistent pain, 24% versus 16% had incident pain, and 29% versus 18% had intermittent pain. A higher BMI was predictive of persistent pain (odds ratio [OR] 1.14, 95% confidence interval [95% CI] 1.04-1.25) and incident pain (OR 1.10, 95% CI 1.02-1.18). The presence of radiographic knee OA was predictive of persistent pain (OR 3.70, 95% CI 1.34-10.28; P = 0.012), and reported knee injury was predictive of both persistent pain (OR 4.13, 95% CI 1.34-12.66; P = 0.013) and intermittent pain (OR 4.25, 95% CI 1.81-9.98; P = 0.001). Conclusion: Significant variability in the temporal fluctuation of self-reported knee pain was seen in this community-based prospective study over a period of 12 years, with few women consistently reporting knee pain at each time point. Distinct baseline predictors for each pain pattern were identified and may explain the observed heterogeneity of self-reported knee pain when pain status is measured at only one time point.

Objective: Malalignment is associated with knee osteoarthritis (KOA), however, the optimal anatomic axis (AA) knee alignment measurement on a standard limb radiograph (SLR) is unknown. This study compares one-point (1P) and two-point (2P) AA methods using three knee joint centre locations and examines cross-sectional associations with symptomatic radiographic knee osteoarthritis (SRKOA), radiographic knee osteoarthritis (RKOA) and knee pain.Methods: AA alignment was measured six different ways using the KneeMorf software on 1058 SLRs from 584 women in the Chingford Study. Cross-sectional associations with principal outcome SRKOA combined with greatest reproducibility determined the optimal 1P and 2P AA method. Appropriate varus/neutral/valgus alignment categories were established using logistic regression with generalised estimating equation models fitted with restricted cubic spline function.Results: The tibial plateau centre displayed greatest reproducibility and associations with SRKOA. As mean 1P and 2P values differed by >2°, new alignment categories were generated for 1P: varus 182° and for 2P methods: varus 185°. Varus vs neutral alignment was associated with a near 2-fold increase in SRKOA and RKOA, and valgus vs neutral for RKOA using 2P method. Nonsignificant associations were seen for 1P method for SRKOA, RKOA and knee pain.Conclusions: AA alignment was associated with SRKOA and the tibial plateau centre had the strongest association. Differences in AA alignment when 1P vs 2P methods were compared indicated bespoke alignment categories were necessary. Further replication and validation with mechanical axis alignment comparison is required.

Objective To establish the natural history of radiographic knee osteoarthritis (OA) over 14 years in a community-based cohort. Methods We examined women from the Chingford Women's Study, a community-based cohort followed up for more than 14 years. We selected women for whom bilateral radiographs of the knees (with the legs in full extension) were obtained at approximately 5-year intervals. Radiographs were scored for OA in a blinded manner, using Kellgren/Lawrence (K/L) grades. Descriptive statistics and odds ratios (ORs) were used to compare the incidence, worsening, and progression of radiographic knee OA. Results A complete radiography series was available for 561 of the original 1,003 subjects enrolled in the study. The median age of these subjects at baseline was 53 years (interquartile range 48–58 years). At baseline, 13.7% of the subjects had radiographic knee OA (K/L grade ≥2) in at least one knee, and the prevalence increased to 47.8% by year 15. The annual cumulative incidence of radiographic knee OA was 2.3% between baseline and year 15. The annual rates of disease progression and worsening between baseline and year 15 were 2.8% and 3.0%, respectively. Subjects with a K/L grade of 1 at baseline were more likely to experience worsening by year 15 compared with subjects with a baseline grade of 0 (OR 4.5, 95% confidence interval 2.7–7.4). Conclusion This is the longest natural history study of radiographic knee OA to date. The results showed relatively low rates for the incidence and progression of radiographic knee OA; more than half of all subjects had no radiographic evidence of knee OA over a 15-year period of time. Subjects with a baseline K/L grade of 1 were more likely than subjects with other baseline K/L grades to experience worsening of knee OA.

Invariant NKT cells (iNKT) are potent immunoregulatory T cells that recognize CD1d via a semi-invariant TCR (iNKT-TCR). Despite the knowledge of a defective iNKT pool in several autoimmune conditions, including rheumatoid arthritis (RA), a clear understanding of the intrinsic mechanisms, including qualitative and structural changes of the human iNKT repertoire at the earlier stages of autoimmune disease, is lacking. In this study, we compared the structure and function of the iNKT repertoire in early RA patients with age- and gender-matched controls. We analyzed the phenotype and function of the ex vivo iNKT repertoire as well as CD1d Ag presentation, combined with analyses of a large panel of ex vivo sorted iNKT clones. We show that circulating iNKTs were reduced in early RA, and their frequency was inversely correlated to disease activity score 28. Proliferative iNKT responses were defective in early RA, independent of CD1d function. Functional iNKT alterations were associated with a skewed iNKT-TCR repertoire with a selective reduction of high-affinity iNKT clones in early RA. Furthermore, high-affinity iNKTs in early RA exhibited an altered functional Th profile with Th1- or Th2-like phenotype, in treatment-naive and treated patients, respectively, compared with Th0-like Th profiles exhibited by high-affinity iNKTs in controls. To our knowledge, this is the first study to provide a mechanism for the intrinsic qualitative defects of the circulating iNKT clonal repertoire in early RA, demonstrating defects of iNKTs bearing high-affinity TCRs. These defects may contribute to immune dysregulation, and our findings could be exploited for future therapeutic intervention.

0 909 551(60.6%) 91(10.0%) 142(15.6%) 111(12.2%) 14(1.5%) 1 57 11(19.3%) 3(5.3%) 22(38.6%) 18(31.6%) 3(5.3%) 2 60 0(0%) 1(1.7%) 30(50.0%) 25(41.7%) 4(6.7%) 3 26 0(0%) 1(3.8%) 4(15.4%) 17(65.4%) 4(15.4%)

Objective To examine longitudinal patterns in body mass index (BMI) over 14 years and its association with knee pain in the Chingford Study. Methods We studied a total of 594 women with BMI data from clinic visits at years (Y) 1, 5, 10, and 15. Knee pain at Y15 was assessed by questionnaire. Associations between BMI over 14 years and knee pain at Y15 were examined using logistic regression. Results BMI significantly increased from Y1 to Y15 (P < 0.0005) with medians (interquartile ranges) of 24.5 kg/m2 (22.5–27.2 kg/m2) and 26.5 kg/m2 (23.9–30.1 kg/m2), respectively. At Y15, 45.1% of subjects had knee pain. A greater BMI at Y1 (odds ratio [OR] 1.34, 95% confidence interval [95% CI] 1.05–1.69), at Y15 (OR 1.34, 95% CI 1.10–1.61), and change in BMI over 15 years (OR 1.40, 95% CI 1.00–1.93) were significant predictors of knee pain at Y15 (P < 0.05). BMI change was associated with bilateral (OR 1.61, 95% CI 1.05–1.76, P = 0.024) but not unilateral knee pain (OR 1.22, 95% CI 0.73–1.76, P = 0.298). The association between BMI change and knee pain was independent of radiographic knee osteoarthritis (OA). The strength of association between BMI and knee pain at Y15 was similar during followup measurements. Conclusion Over 14 years, a higher BMI predicts knee pain at Y15 in women, independently of radiographic knee OA. When adjusted, the association was significant in bilateral, not unilateral, knee pain, suggesting alternative pathologic mechanisms may exist. The longitudinal effect of BMI on knee pain at Y15 is equally important at any time point, which may assist reducing the population burden of knee pain.

Multi-segment three-dimensional analysis is a complex yet rapidly evolving methodology in podiatric mechanical research. The purpose of this study was to explore the within-subject foot motion variability (MoVa) during the stance phase of gait.

Background Innate mechanisms of inflammation control are central to the pathogenesis of autoimmune diseases (AID), including RA. Invariant Natural Killer T cells (iNKT) are a highly conserved T-cell subset with key roles in immune tolerance. iNKT-targeting therapeutic approaches are highly effective in animal models, but translation to human AID has not yet succeeded. Objectives We have previously defined the human iNKT repertoire according to the clonal distribution of high- and low-affinity iNKT T-cell receptors 1 . Here we have investigated the iNKT repertoire with regard to function and T-cell receptor affinity in early Rheumatoid Arthritis. Methods 100 early RA patients and 50 matched healthy people were included. Multiple iNKT clones from patients and controls were generated and analysed for TCR affinity to the restriction element human CD1d by using different CD1d/ligand-tetramers; Clones were analysed for cytokine secretion in response to CD1d/antigen and mitogen stimulation; iNKT frequency and CD1d expression on antigen presenting cells were determined by FACS; in vitro expansion of iNKT cells to antigen-pulsed autologous monocytes and recombinant CD1d/antigen coated beads was compared to differentiate inherent iNKT cell defects from defects in antigen presentation. Results The clonal repertoire of iNKT cells in healthy controls shows a broad distribution with regard to iNKT receptor affinity for CD1d. In contrast, the repertoire is highly significantly shifted towards lower-affinity iNKT clones in age-matched early RA. This shift correlates with DAS28. Analysis of untreated vs treated early RA patients shows that the iNKT repertoire is “restored to normal” in the DMARD group, and this correlates with DAS28. CD1d expression on antigen-presenting cells was not different between groups. iNKT cells in all early RA patients exhibited a bias in cytokine secretion towards Th1 cytokines, independent of CD1 antigen processing. Conclusions This is the first demonstration of changes in a T-cell compartment based on TCR-affinity during disease. The repertoire of iNKT cells in blood is significantly changed in early treatment-naive RA, with loss of higher-affinity iNKT TCR bearing cells that may have key roles in immunological tolerance. Our findings are relevant for all iNKT cell targeting approaches in humans, including those designed for restoring tolerance in AID, and also those designed for promoting inflammation in cancer or infection. References Matulis G, et al. PLoS Biol. 2010; 22;8(6):e1000402. doi: 10.1371/journal.pbio.1000402. Acknowledgements Funded by Arthritis Research UK (to SDG) Disclosure of Interest None Declared

Data were obtained during packaging operations in potato packinghouses, after shipment to market in highway trucks, during unloading at wholesale warehouses, and during marketing at retail stores. These data represent the performance of the packing methods and materials, the cost of labor and materials (excluding trucking) to the shipper, and the quality of the product when handled and shipped with three methods of unitizing and palletizing. The report summarizes the labor, materials, and depreciated special equipment costs/ 16, 330-kg truckload synthesized for three methods, each with two package sizes. The total cost of the strap/angleboard method was about 9%less than that of the paper-baler-bag method for packing and palletizing 2.27-kg consumer packages and about 20%less than that of the paper-baler-bag method for packing and palletizing 4.54-kg consumer packages. The corrugated-fiberboard master container method cost about 28%more than the paper-baler-bag method for packing and palletizing 2.27-kg consumer packages and about 31 %more than the paper-baler-bag method for packing and palletizing 4.54-kg consumer packages.