Relationship between first tarsometatarsal ligament morphology and its continuity with the fibularis longus and first tarsometatarsal joint degeneration.

This study explored the relationship between the morphological characteristics of the first tarsometatarsal ligaments and fibularis longus (FL) and the severity of articular cartilage degeneration in the first tarsometatarsal joint. Sixty legs from 30 cadavers were examined. The plantar, dorsal, and medial first tarsometatarsal ligaments were classified by fiber bundle number, and their morphological characteristics (fiber bundle length, width, thickness) were measured. The FL was categorized by its continuity with the plantar first tarsometatarsal ligament (PTML): Type A, connection with the PTML only on the first metatarsal; Type B, connection along the entire PTML; and Type C, no connection with the PTML. The severity of articular cartilage degeneration was assessed in four stages. No significant differences in cartilage degeneration among ligament types were found. Negative correlations were observed between the fiber bundle width and thickness of the PTML and the severity of cartilage degeneration. FL was classified as Type A in 68%, Type B in 27%, and Type C in 5% of feet. The fiber bundle thickness of the PTML in Type B was greater than in other types. Our findings suggest that smaller fiber bundle width and thickness in the PTML may be associated with severe cartilage degeneration. The FL had continuity with the PTML in 95% of feet and could enhance the mechanical strength of the PTML in Type B feet.

Conventional versus ultrasound treat to target: no difference in magnetic resonance imaging inflammation or joint damage over 2 years in early rheumatoid arthritis.

OBJECTIVE: To investigate whether an ultrasound-guided treat-to-target strategy for early RA would lead to reduced MRI inflammation or less structural damage progression compared with a conventional treat-to-target strategy. METHODS: A total of 230 DMARD-naïve early RA patients were randomized to an ultrasound tight control strategy targeting DAS <1.6, no swollen joints and no power Doppler signal in any joint or a conventional strategy targeting DAS <1.6 and no swollen joints. Patients in both arms were treated according to the same DMARD escalation strategy. MRI of the dominant hand was performed at six time points over 2 years and scored according to the OMERACT RA MRI scoring system. A total of 218 patients had baseline and one or more follow-up MRIs and were included in the analysis. The mean MRI score change from baseline to each follow-up and the 2 year risk for erosive progression were compared between arms. RESULTS: MRI bone marrow oedema, synovitis and tenosynovitis improved over the first year and was sustained during the second year of follow-up, with no statistically significant differences between the ultrasound and the conventional arms at any time point. The 2 year risk for progression of MRI erosions was similar in both treatment arms: ultrasound arm 39%, conventional arm 33% [relative risk 1.16 (95% CI 0.81, 1.66), P = 0.40]. CONCLUSION: Incorporating ultrasound information in treatment decisions did not lead to reduced MRI inflammation or less structural damage compared with a conventional treatment strategy. The findings support that systematic use of ultrasound does not provide a benefit in the follow-up of patients with early RA. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, http://clinicaltrials.gov, NCT01205854.

ACPA-positive versus ACPA-negative rheumatoid arthritis: two distinct erosive disease entities on radiography and ultrasonography.

The objective of this study is to assess the prevalence, localization, and severity of bone erosions on radiography (RX) and ultrasonography (US) according to ACPA status in patients with rheumatoid arthritis (RA). 78 patients with ACPA-positive (ACPA+) RA and 30 patients with ACPA-negative (ACPA-) RA fulfilling the ACR 1987 and/or ACR/EULAR 2010 criteria were consecutively included. On RX, a modified Sharp erosion score (SHSe) was evaluated by two blinded readers and one adjudicator for discordant cases (number of eroded joints ≤ three). On US, erosions were scored on six bilateral joints (MCP2, 3, 5; MTP2, 3, 5) with a four-point scale to calculate the total US score for erosions (USSe). The mean total SHSe and USSe were 3.7 and 4.4 times higher in the ACPA+ group than in the ACPA- group, respectively (P < 0.001). On both RX and US, the most discriminating joint between the two groups was MTP5, especially in cases with bilateral erosion. Based on multivariate analyses, ACPA + status was associated with erosive RA on RX according to the EULAR 2013 definition criteria [OR 4.4 (95% CI 1.2-16.4)], and on US according to the following two definitions: the presence of at least two eroded joint facets [OR 3.7 (95% CI 1.4-9.9)] or at least one grade 2 joint facet erosion [OR 9.0 (95% CI 2.8-28.4)]. Compared to ACPA- RA, ACPA + RA is associated independently with more severe erosive disease on RX and US. Both US and RX bilateral erosions in MTP5 joints are highly discriminant for ACPA + RA patients (97.8% in US and 100% in RX).

Pigmented villous nodular synovitis mimicking metastases on 18F-FDG PET/CT in a patient with rectal mucosal melanoma: a case report.

BACKGROUND: Mucosal melanomas are rare and have a high potential for metastasizing. Surgical resection is the treatment of choice for single distant metastases. Malignant melanoma usually shows the highest uptake of fluorine-18 fluorodeoxyglucose (18F-FDG). 18F- FDG positron emission tomography /computed tomography (PET/CT) is usually used for melanoma staging. An extensive literature review revealed only 4 published case reports and an original paper involving 8 cases (12 cases in total) of patients with skin melanomas in whom pigmented villous nodular synovitis (PVNS) mimicked metastatic melanoma, however, none of the melanomas reported were of rectal mucosal origin. CASE PRESENTATION: A 60-year-old woman presented with recent diagnosis of rectal mucosal melanoma, two additional 18F-FDG-avid lesions in the left ankle and left foot were detected on 18F-FDG PET/CT. Metastases were initially suspected; however, the final diagnosis was PVNS. CONCLUSIONS: This is the first report of PVNS mimicking metastases on 18F-FDG PET/CT in a patient with rectal mucosal melanoma. Although high 18F-FDG-avid lesions in patients with rectal mucosal melanoma are highly suspected to be metastasis and warrant an meticulous examination, the present case is a reminder that in such patients, not all lesions with high 18F-FDG uptake, especially those near a joint, are metastases and that more extensive resection is unnecessary.

Relationship of callosities of the forefoot with foot deformity, Health Assessment Questionnaire Disability Index, and joint damage score in patients with rheumatoid arthritis.

Objectives: We aimed to investigate the relationship of callosities of the forefoot with foot deformity, the Health Assessment Questionnaire Disability Index (HAQ-DI) and modified total Sharp score (TSS) in patients with rheumatoid arthritis (RA).Methods: A total of 202 patients and 404 feet were enrolled. We examined the prevalence of callosities. Clinical data included the HAQ-DI, TSS, hallux valgus angle (HVA), and calcaneal pitch angle (CPA). The analysis of factors associated with callosities of the forefoot was performed by comparing patients with and without callosities of the forefoot.Results: The prevalence of callosities was 31.2% of all patients and 24.0% of all feet. The patients with callosities of the forefoot had significantly higher TSS of the foot. The presence of callosities affected the HAQ-DI walking score. HVA and CPA were identified as being associated with callosities of the forefoot. Analyzing from the cutoff values, the odds ratios of HVA, CPA, and HVA and (combined) CPA were 4.64, 1.73, and 2.99, respectively.Conclusion: Hallux valgus and flatfoot were related to callosities of the forefoot in RA. This study suggested that to prevent callosities of the forefoot, early diagnosis and foot care for hallux valgus and flatfoot are needed in daily practice.

Microwave Radiometry-Derived Thermal Changes of Small Joints as Additional Potential Biomarker in Rheumatoid Arthritis: A Prospective Pilot Study.

OBJECTIVE: A prospective pilot study was performed using microwave radiometry (MR), a noninvasive method detecting in-depth tissue temperature, to evaluate whether temperature-of-small-joint-derived scores correlate to parameters commonly used to assess disease activity in rheumatoid arthritis (RA). METHODS: Ten patients with active, untreated RA underwent clinical and laboratory assessments and joint ultrasound and MR of hand and foot small joints at baseline and at 15, 30, and 90 days after treatment onset. Mixed-model analysis for repeated measures was used to compare patient characteristics in sequential visits. Twenty age- and sex-matched healthy individuals served as control subjects. RESULTS: Using 1248 MR-derived separate recordings from patients' joints, several thermoscores involving different joint combinations were created. When compared with clinical and ultrasound data, the best performing thermoscore involved temperatures of 16 joints (second to fifth metacarpal and proximal interphalangeal joints, bilaterally). This thermoscore correlated to the 28-joint Disease Activity Score-C-reactive protein, tender and swollen joint counts, patient's visual analog scale (all P ≤ 0.02), and the standard 7-joint ultrasound score (P < 0.03) and could also discriminate patients in high (mean, 9.2 [SD, 5.6]) or moderate (7.1 [SD, 3.5]) versus low disease activity/remission (4.2 [SD, 1.8]) (P ≤ 0.01) or healthy subjects (5.0 [SD, 1.7]) (P = 0.002). CONCLUSIONS: Microwave radiometry-derived increased in-depth temperature indicative of local inflammation of small joints may serve as an additional biomarker in RA. Optimization of MR-based methods may result in objective assessments of RA disease activity in clinical practice.

Tofacitinib attenuates arthritis manifestations and reduces the pathogenic CD4 T cells in adjuvant arthritis rats.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by pronounced inflammation and leukocyte infiltration in affected joints. Tofacitinib is new agent, a selective inhibitor of Janus kinase (JAK) signaling pathways mediated by JAK1 and JAK3 and inhibits the key transcription factors STAT1 and STAT3. We investigated the action mechanisms of tofacitinib in rats with adjuvant-induced-arthritis (AIA). AIA-rats were treated orally with tofacitinib or with methotrexate. Arthritis severity and serum C-reactive protein (CRP) levels were evaluated, splenic cells were examined by flow cytometry and cytokines were analyzed by real-time PCR. Tofacitinib markedly reduced the clinical status of treated rats in comparison to control group. Reduced joints inflammation and down-regulated serum CRP levels reflected the clinical manifestations of the treated rats. Tofacitinib down-regulated significantly the frequency of CD4+IFN-γ+ T cells and reduced IL-1ß mRNA expression levels in the spleen of the treated rats. These results show that tofacitinib attenuated arthritis severity, modified splenic populations and cytokine imbalance.

Multimodality scoring of chondral injuries in the equine fetlock joint ex vivo.

OBJECTIVE: We investigate the potential of a prototype multimodality arthroscope, combining ultrasound, optical coherence tomography (OCT) and arthroscopic indentation device, for assessing cartilage lesions, and compare the reliability of this approach with conventional arthroscopic scoring ex vivo. DESIGN: Areas of interest (AIs, N = 43) were selected from equine fetlock joints (N = 5). Blind-coded AIs were independently scored by two equine surgeons employing International Cartilage Repair Society (ICRS) scoring system via conventional arthroscope and multimodality arthroscope, in which high-frequency ultrasound and OCT catheters were attached to an arthroscopic indentation device. In addition, cartilage stiffness was measured with the indentation device, and lesions in OCT images scored using custom-made automated software. Measurements and scorings were performed twice in two separate rounds. Finally, the scores were compared to histological ICRS scores. RESULTS: OCT and arthroscopic examinations showed the highest average agreements (55.2%) between the scoring by surgeons and histology scores, whereas ultrasound had the lowest (50.6%). Average intraobserver agreements of surgeons and interobserver agreements between rounds were, respectively, for conventional arthroscope (68.6%, 69.8%), ultrasound (68.6%, 68.6%), OCT (65.1%, 61.7%) and automated software (65.1%, 59.3%). CONCLUSIONS: OCT imaging supplemented with the automated software provided the most reliable lesion scoring. However, limited penetration depth of light limits the clinical potential of OCT in assessing human cartilage thickness; thus, the combination of OCT and ultrasound could be optimal for reliable diagnostics. Present findings suggest imaging and quantitatively analyzing the entire articular surface to eliminate surgeon-related variation in the selection of the most severe lesion to be scored.

Anethole reduces inflammation and joint damage in rats with adjuvant-induced arthritis.

AIM: This study evaluated whether anethole attenuates the inflammatory response and joint damage in a model of adjuvant-induced arthritis (AIA) in rats. METHODS: The animals were treated with 62.5-, 125-, or 250-mg/kg anethole daily for 21 days after AIA and necropsied on days 14 and 21 to evaluate the number of serum and synovial leukocytes (total and differential), serum cytokines (IL-2, IL-6, IL-12, IL-17, and TNF-α), and nitric oxide concentrations. Morphologic changes in the cartilage and bone of the femorotibial articulation in both left paw and right paw were studied in hematoxylin/eosin and Sirius Red-hematoxylin sections. RESULTS: Different doses of anethole suppressed paw swelling and the number of serum and synovial leukocytes. However, 250 mg/kg of anethole more effectively controlled local and systemic inflammation. Histological evaluation revealed significant prevention of cartilage damage and inflammatory infiltrate scores. Morphometric analysis showed pannus formation, the thickness of the articular cartilage, and bone resorption lower in the anethole-treated AIA group compared to untreated AIA group on both days 14 and 21. These significant anti-inflammatory effects in the anethole-treated AIA group were associated with downregulation of cytokines and nitric oxide levels. CONCLUSION: Therefore, anethole may be a useful intervention to treat inflammatory arthritis.

Outcomes of modified metatarsal shortening offset osteotomy for forefoot deformity in patients with rheumatoid arthritis: Short to mid-term follow-up.

OBJECTIVES: Advances in drug therapy for rheumatoid arthritis (RA) have been encouraging us to preserve the metatarsopharangeal (MTP) joint in correction of forefoot deformities, and original metatarsal shortening offset osteotomy was recommended as one of the conventional surgical options for forefoot deformities in RA cases. The objective of this study was to evaluate short- to mid-term outcomes of modified metatarsal shortening offset osteotomy. METHODS: A retrospective observational study was completed for 80 RA cases (mean follow-up period: 3.2 years) who underwent modified metatarsal shortening offset osteotomy. Both lesser toe scales and RA foot ankle scales were administered using the Japanese Society for Surgery of the Foot (JSSF) standard rating system, and a postoperative self-administered foot evaluation questionnaire (SAFE-Q) at final follow-up was also checked to evaluate clinical outcomes. RESULTS: This procedure significantly improved clinical scores of both the JSSF [lesser toes and RA foot and ankle] scales. Of 80 feet, 24 (30%) showed recurrence of MTP joint subluxation/dislocation. Furthermore, the feet in the recurrence group showed significant varus hindfoot. On the other hand, valgus foot in the recurrence group more frequently included midfoot bony ankyloses. All of the affected feet showed the limitation of MTP joints (<70°) after surgery. CONCLUSIONS: Modified metatarsal shortening offset osteotomy was recommended for RA forefoot disorders as one of the joint preservation surgeries in short- to mid-term follow-up. However, some modifications to avoid limitation of ROM in the MTP joint are required. It must be borne in mind that varus hindfoot and/or bony ankyloses in the mid-hindfoot can cause recurrence of dorsal dislocation/subluxation of the lesser toe MTP joint.

Short-term effect of ultrasound-guided low-molecular-weight hyaluronic acid injection on clinical outcomes and imaging changes in patients with rheumatoid arthritis of the ankle and foot joints. A randomized controlled pilot trial.

To determine whether hyaluronic acid (HA) injection into rheumatoid arthritis ankles and feet can achieve improvement in foot function and reduce synovial hyper-vascularization. Forty-four patients with RA having unilateral or bilateral painful ankle and foot involvement (N = 75) were studied. All the patients were randomized to receive HA (N = 40) or lidocaine (LI) (N = 35) injection at 2-week intervals; Clinical assessments were performed using a visual analog scale (VAS) and foot function index (FFItotal) including subscales of pain (FFIpain) before injection at baseline, 4 weeks (first evaluation) and 12 weeks (secondary evaluation). Imaging evaluation based on color Doppler ultrasound (CDUS) and synovitis scores was performed simultaneously. HA injection improved the VAS score (p = .009), FFIpain (p = .041), and FFItotal (p = .032) considerably more than LI injections did at the first evaluation. The CDUS values at first evaluation (p = .005) and secondary evaluation (p < .001) decreased significantly compared with the base line values. HA injections reduced the CDUS values of more than half of the joints (54%, p = .042) while the control group exhibited no change (20%, p = .56). However, HA injection did not reduce the CDUS values more than LI injection did. Regarding the evaluation of synovial hypertrophy, no significant difference was observed between or within the groups in the synovitis scores. HA injection improved short-term foot function and pain reduction. HA injection may have a modest effect in reducing synovial hyper-vascularization. Further large-scale study is warranted to confirm this result.

Btk inhibition treats TLR7/IFN driven murine lupus.

Bruton's tyrosine kinase (Btk) is expressed in a variety of immune cells and previous work has demonstrated that blocking Btk is a promising strategy for treating autoimmune diseases. Herein, we utilized a tool Btk inhibitor, M7583, to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon. In BXSB-Yaa lupus mice, Btk inhibition reduced autoantibodies, nephritis, and mortality. In the pristane-induced DBA/1 lupus model, Btk inhibition suppressed arthritis, but autoantibodies and the IFN gene signature were not significantly affected; suggesting efficacy was mediated through inhibition of Fc receptors. In vitro studies using primary human macrophages revealed that Btk inhibition can block activation by immune complexes and TLR7 which contributes to tissue damage in SLE. Overall, our results provide translational insight into how Btk inhibition may provide benefit to a variety of SLE patients by affecting both BCR and FcR signaling.

To what extent is foot pain related to biomechanical changes and ultrasound-detected abnormalities in rheumatoid arthritis?

OBJECTIVES: To investigate the presence of biomechanical abnormalities and ultrasound (US)-detected inflammation and damage in low disease or remission status rheumatoid arthritis (RA) patients with foot complaints. METHODS: We recruited 136 subjects with foot complaints. Sixty-two were biologic disease-modifying antirheumatic drug-treated RA patients presenting Disease Activity Score-determined remission or low disease activity while the remaining 74 were gender matched controls without rheumatic or musculoskeletal disorders. Both groups underwent a comprehensive podiatric, biomechanical and B-mode and Doppler US assessment of the feet. RESULTS: Most RA patients and controls were female (77.4% and 83.8%, respectively). There was no statistical difference in the proportion of obese subjects in either group (p=0.792). Inappropriate shoes were used by 50.0% of RA patients and 33.8% of controls (p=0.080). Talalgia, particularly heel pain, was more frequent in the control group, with associated talalgia and metatarsalgia being more prevalent in the RA group (p<0.05). The RA patient group was also more likely to present greater foot deformity, more limited joint movement and biomechanical abnormalities than the controls (p<0.05). US inflammatory and structural changes were significantly more frequent in RA patients than in controls (p<0.05). US structural involvement was significantly associated with limited joint mobility and pathologic biomechanical tests only in RA patients (p<0.05). CONCLUSIONS: RA foot complaints seemed to be linked to US-detected RA involvement and biomechanical abnormalities. Podiatric and US assessments can be useful to help the clinician to optimise the management of RA patients in remission/low disease activity with foot complaints.

The establishment of a porcine rheumatoid arthritis model: Collagen induced arthritis minipig model.

Rheumatoid arthritis (RA) research has been largely dependent on collagen induced arthritis (CIA) rodent models, however, they may not translate well to humans due to innate differences in the size, physiology and lifespan. The present study aimed to establish a CIA porcine model with the physical, hematological, histopathological and etiological properties closer to their human equivalent in an attempt to better meet the needs of RA research. Three month old minipigs were administered of bovine type II collagen (CII) emulsified with complete Freund's adjuvants on Day 1 and incomplete Freund's adjuvants on Day 22, via an intradermal or intra-articular route. The clinical, radiological and hematological assessments of immunized animals were made periodically until Day 43, during which period the onset and progression of arthritis was recorded and characterized. In addition, the histopathological and micro-tomographic assessments of the cartilage degradation with regard to mononuclear cell infiltration, and joint deformity indicated a higher severity in the intradermal injection group over the intra-articular group. With confirmation of the susceptibility to heterogeneous CII for arthritis induction in minipig, the potential suitability of this test system as a large animal model for RA has been demonstrated.

Evaluating processes underlying the predictive value of baseline erosions for future radiological damage in early rheumatoid arthritis.

OBJECTIVES: Baseline erosions are characteristic for rheumatoid arthritis (RA) and predictive for a severe disease course. The mechanisms leading to baseline erosions being a strong predictor for radiological progression are unknown. We aimed to increase this understanding by mediation analyses in an observational cohort and a cross-sectional MRI study. METHODS: 3256 hands and feet radiographs of 653 early RA patients assessed during 7 years of disease were scored using the Sharp-van der Heijde method. Mediation models and multivariate regression analyses were used to explore the association between baseline erosions, other predictors and radiological damage over time. 603 joints (MCP2-5 and MTP1-5) of 67 RA patients underwent 1.5 T MRI at baseline. Data on MRI inflammation were compared with clinical inflammation and baseline radiological erosions. RESULTS: Patients with baseline erosions had, at any point in time during 7 years, 3.45 times more joint damage than patients without erosions (p<0.001, 95% CI 3.00 to 3.98). Baseline erosions were an independent predictor and not a mediator between symptom duration, systemic or local clinical inflammation (erythrocyte sedimentation rate (ESR), swollen joint count (SJC)) or autoantibodies (anti-citrullinated-peptide antibodies, rheumatoid factor) and radiological damage. Subclinical MRI inflammation was studied in relation to erosions, revealing that 83% of the non-swollen joints with baseline erosions had subclinical MRI inflammation compared with 25% of the non-swollen joints without baseline erosions (OR 15.2 95% CI 3.1 to 102.1). The association between MRI inflammation and baseline erosions was independent of symptom duration, ESR, SJC and autoantibodies. CONCLUSIONS: Baseline erosions are a predictor for future joint damage, independent of known predictors as time, autoantibodies or clinical measurable inflammation. Subclinical inflammation is suggested as an underlying mechanism.

Relationship between structural joint damage and urate deposition in gout: a plain radiography and dual-energy CT study.

OBJECTIVES: The aim of this work was to examine the relationship between joint damage and monosodium urate (MSU) crystal deposition in gout. METHODS: Plain radiographs and dual-energy CT (DECT) scans of the feet were prospectively obtained from 92 people with tophaceous gout. Subcutaneous tophus count was recorded. The ten metatarsophalangeal joints were scored on plain radiography for Sharp-van der Heijde erosion and joint space narrowing (JSN) scores, and presence of spur, osteophyte, periosteal new bone and sclerosis (920 total joints). DECT scans were analysed for the presence of MSU crystal deposition at the same joints. RESULTS: DECT MSU crystal deposition was more frequently observed in joints with erosion (OR (95% CI) 8.5 (5.5 to 13.1)), JSN (4.2 (2.7 to 6.7%)), spur (7.9 (4.9 to 12.8)), osteophyte (3.9 (2.5 to 6.0)), periosteal new bone (7.0 (4.0 to 12.2)) and sclerosis (6.9 (4.6 to 10.2)), p<0.0001 for all. A strong linear relationship was observed in the frequency of joints affected by MSU crystals with radiographic erosion score (p<0.0001). The number of joints at each site with MSU crystal deposition correlated with all features of radiographic joint damage (r>0.88, p<0.05 for all). In linear regression models, the relationship between MSU crystal deposition and all radiographic changes except JSN and osteophytes persisted after adjusting for subcutaneous tophus count, serum urate concentration and disease duration. CONCLUSIONS: MSU crystals are frequently present in joints affected by radiographic damage in gout. These findings support the concept that MSU crystals interact with articular tissues to influence the development of structural joint damage in this disease.

Pain sensitization and degenerative changes are associated with aberrant plantar loading in patients with painful knee osteoarthritis.

OBJECTIVES: This study focused on the biomechanical implications of knee osteoarthritis (OA) and the association with pain. The plantar loading force distribution of the foot was determined and correlated to degenerative knee changes, function, pain intensity, and pain sensitization. METHOD: Knee OA patients (n = 34) with moderate and mild knee pain were characterized and compared to matched controls (n = 16). The Plantar Foot Posture Index (FPI) and mean maximum plantar forces were determined by pressure-sensitive insoles. Pain intensity and function were assessed by the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and the Brief Pain Inventory (BPI). Local knee pain sensitization was assessed by pressure pain thresholds (PPTs) from eight knee locations. Spreading sensitization was assessed by PPTs from two extra-segmental test sites. Temporal summation to repeated pressure stimulation (knee and extra-segmental stimulation) and conditioning pain modulation (CPM) were assessed, representing central pain mechanisms. RESULTS: The maximum force (MF) applied by the medial forefoot correlated to knee PPTs (r = 0.524, p < 0.001), CPM potency (r = 0.532, p < 0.001), and BPI (r = -0.325, p < 0.05) and WOMAC scores (pain r = -0.425, p < 0.01; stiffness r = -0.386, p < 0.01; function r = -0.378, p < 0.05). The MF applied by the medial hindfoot correlated negatively to scores on the FPI (r = -0.394, p < 0.01) and the Kellgren-Lawrence (K-L) grading scale (r = -0.330, p < 0.05). The MF applied by the medial forefoot correlated to extra-segmental PPTs (r = 0.554, p < 0.001) and the potency of CPM (r = 0.561, p < 0.0001). The MF applied by the lateral hindfoot correlated negatively to the PPT assessed extra-segmentally (r = -0.367, p < 0.05) and positively to CPM potency (r = 0.322, p < 0.05). CONCLUSIONS: This study shows that mean maximum plantar foot force distribution in patients with painful knee OA is associated with specific pain mechanisms, function, radiological findings, and pain intensity.

Biomechanics of the Ageing Foot and Ankle: A Mini-Review.

Foot pain is highly prevalent in older people and has a significant detrimental impact on mobility and quality of life. In recent years, there has been increased interest in exploring the biomechanical factors that may contribute to the development of foot disorders and the associated impairment of mobility in this age group. Studies have shown that with advancing age, there is a general tendency for the foot to exhibit increased soft tissue stiffness, a decreased range of motion, decreased strength and a more pronated posture as well as to function in a more pronated position with reduced joint mobility and less efficient propulsion when walking. These changes may contribute to the development of foot pain, impair performance in functional weight-bearing activities and increase the risk of falls. However, plantar pressure analysis technology has considerable potential to assist in optimising the design of interventions to redistribute load away from high-pressure areas, thereby alleviating foot symptoms and improving mobility in older people.

Anti-inflammatory and anti-arthritic effects of 3-hydroxy, 2-methoxy sodium butanoate from the leaves of Clerodendrum phlomidis L.f.

INTRODUCTION: The leaves of Clerodendrum phlomidis L.f. have been used in the Indian traditional system of medicine to treat several inflammatory diseases and arthritis. The aim of the present study was to assess the anti-inflammatory and anti-arthritic activities of the leaves of C. phlomidis and to isolate the active principle by bioactivity guided fractionation. MATERIALS AND METHODS: To find the anti-inflammatory constituents from this plant, fractionations were performed with concurrent bioassays. Carrageenan-induced inflammation and Freund complete adjuvant (FCA)-induced arthritic rat models were used. The anti-inflammatory and anti-arthritic activities of the isolated compound were studied by assessing the histology of the joints, levels of lysosomal enzymes, protein-bound carbohydrates, acute phase protein, etc., in plasma, as well as by estimating the levels and expression of pro-inflammatory cytokines in the joints. RESULTS: Repeated fractionations and bioassays yielded a novel bioactive compound: 3-hydroxy, 2-methoxy-sodium butanoate. Treatment with this compound reduced the paw edema induced by carrageenan and FCA dose dependently. The levels of lysosomal enzymes and protein-bound carbohydrates decreased significantly upon treatment with the compound. The level of plasma acute phase protein was also decreased compared with control animals. Protein levels and mRNA expression of pro-inflammatory cytokines TNF, IL-1 and IL-6 in the joints were decreased significantly in a dose-dependent manner and the histopathological data also added evidence of the anti-arthritic property of the compound. CONCLUSION: The 3-hydroxy,2-methoxy sodium butanoate isolated from plant leaves displays considerable potency in anti-inflammatory action and has a prominent anti-arthritic effect. This is the first report of this natural compound with bioactivity.

Light and electron microscopic detection of inflammation-targeting liposomes encapsulating high-density colloidal gold in arthritic mice.

OBJECTIVE: We have previously demonstrated the efficient and time-dependent transvascular localization of Sialyl Lewis X (SLX)-liposomes to inflammatory sites, but the final target of the SLX-liposomes remained uncertain. The aim of this study was to identify the target cells of the liposomes within the inflamed joints of collagen antibody-induced arthritis (CAIA) model mice. METHODS: SLX-liposomes and unlabeled liposomes encapsulating high-density colloidal gold were administered intravenously into the caudal vein of CAIA mice on day 5 after induction of arthritis when the inflammatory score was maximal (n = 6 per group). Six hours or 24 h after liposome administration, animals were euthanized and hind limbs and ankles were excised without perfusion. After fixation, synovial tissues were examined by light microscopy after silver enhancement of colloidal gold or by transmission electron microscopy. RESULTS: Silver-enhanced signals were detected within the cells around E-selectin-positive blood vessels in the synovium of the SLX-liposome group. These cells were positive for the macrophage/monocyte marker F4/80 or neutrophil marker Ly-6G. Transmission electron microscopy detected the colloidal gold signals together with liposome-like structures within the phagosomes of synovial macrophages. Transmission electron microscopy and energy dispersive X-ray spectrometry could determine gold elements in the lysosomes of synovial macrophages. CONCLUSIONS: The results of the current study demonstrate that SLX-liposomes primarily targeting E-selectin in activated endothelial cells could potentially deliver their contents into inflammatory cells around synovial blood vessels in arthritic joints.