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To investigate age related and site specific variations in turnover and chemistry of the collagen network in healthy tendons as well as the role of collagen remodelling in the degeneration of the supraspinatus tendon (ST-D) in rotator cuff tendinitis. Collagen content and the amount of hydroxylysine (Hyl), hydroxy-lysylpyridinoline (HP), lysylpyridinoline (LP), and the degree of non-enzymatic glycation (pentosidine) were investigated in ST-D and in normal human supraspinatus (ST-N) and biceps brachii tendons (BT-N) by high-performance liquid chromatography. In BT-N, tendons that served as control tissue as it shows rarely matrix abnormalities, pentosidine levels rise linearly with age (20-90 years), indicating little tissue remodelling (resulting in an undisturbed accumulation of pentosidine). A similar accumulation was observed in ST-N up to 50 years. At older ages, little pentosidine accumulation was observed and pentosidine levels showed large interindividual variability. This was interpreted as remodelling of collagen in normal ST after age 50 years because of microruptures (thus diluting old collagen with newly synthesised collagen). All degenerate ST samples showed decreased pentosidine levels compared with age matched controls, indicating extensive remodelling in an attempt to repair the tendon defect. Collagen content and the amount of Hyl, HP, and LP of ST-N and BT-N did not change with age. With the exception of collagen content, which did not differ, all parameters were significantly (p < 0.001) lower in BT-N. The ST-D samples had a reduced collagen content and had higher Hyl, HP, and LP levels than ST-N (p < 0.001).

Inasmuch as Hyl, HP, and LP levels in ST-N did not change with age, tissue remodelling as a consequence of microruptures does not seem to affect the quality of the tendon collagen. On the other hand, the clearly different profile of post-translational modifications in ST-D indicates that the newly deposited collagen network in degenerated tendons is qualitatively different. It is concluded that in ST-D the previously functional and carefully constructed matrix is replaced by aberrant collagen. This may result in a mechanically less stable tendon; as the supraspinatus is constantly subjected to considerable forces this could explain why tendinitis is mostly of a chronic nature.

Retrospective review. The aim of this study was to identify whether a concomitant diagnosis of fibromyalgia (FM) influences postoperative complications, readmission rates or cost following primary 1 to 2 level lumbar fusions in an elective setting. Patients with FM often are limited by chronic lower back pain, many of whom will seek operative treatment. No previous study has evaluated whether patients with a concomitant diagnosis of FM have more complications following spine surgery. Medicare data (2005-2014) from a national database was queried for patients who underwent primary 1 to 2 level posterolateral lumbar spine fusion for degenerative lumbar pathology. Thirty- and 90-day postoperative complication rates, readmission rates, and treatment costs were queried. To reduce confounding, FM patients were matched with a control cohort of non-FM patients using patient demographics, treatment modality, and comorbid conditions, and then analyzed by multivariable logistic regression. Within the first 30-day postoperative, acute post hemorrhagic anemia (odds ratio [OR]: 2.58; P < 0.001) and readmission rates were significantly higher in FM patients compared to controls. There was no significant difference in wound related complications within first 30-days (0.19% vs. 0.23%; P = 0.520) or with length of stay (3.60 vs. 3.53 days; P = 0.08). Within 90-day postoperative, FM patients had higher rates of pneumonia (OR: 3.73; P < 0.001) and incurred 5.31% more in hospital charges reimbursed compared to the control cohort. 3.

Primary 1 to 2 level lumbar fusions performed on FM patients have higher rates of postoperative anemia, pneumonia, cost of care, and readmission compared to match controls. FM patients and surgeons should be aware of these increased risks in an effort to control hospital costs and potential complications.

Neuropathic pain syndrome is characterized by chronic, stimulus-independent pain sensation accompanied by hyperalgesia/allodynia and paresthesia. Fibromyalgia (FM) syndrome displays such features. The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Pain Scale is an instrument developed and validated to recognize neuropathic pain and set it apart from nociceptive pain. This study assessed the responses of patients with FM versus patients with rheumatoid arthritis (RA) to the LANSS Pain Scale questionnaire. Twenty patients with FM and 20 patients with RA answered the Fibromyalgia Impact Questionnaire and LANSS Pain Scale questions related to the following neuropathic sensory disturbance domains: dysesthetic, autonomic, evoked, paroxysmal, and thermal. Pain severity was similar in both groups according to visual analog scale values (5.3 +/- 3.0 for FM v 5.4 +/- 3.1 for RA). There were sharp differences between FM and RA groups in the percentage of affirmative responses to 4 of 5 sensory disturbance questions: dysesthetic (95 v 30), evoked (95 v 35), paroxysmal (90 v 15), and thermal (90 v 20); P <.0001 for each comparison. The LANSS Pain Scale items may become a useful, easily applied bedside test to differentiate FM pain from the nociceptive pain present in RA and in similar arthritic illnesses.

The high prevalence of associated sensory disturbances supports the notion that FM is a neuropathic pain syndrome.

Osteoarthritis (OA) is the most common cause of disability in the elderly. Clinical frailty is associated with high mortality, but few studies have explored the relationship between OA and frailty. The objective of this study was to consider the association between OA and frailty/pre-frailty in an elderly population comprised of six European cohorts participating in the EPOSA project. Longitudinal study using baseline data and first follow-up waves, from EPOSA; 2,455 individuals aged 65-85 years were recruited from pre-existing population-based cohorts in Germany, Italy, the Netherlands, Spain, Sweden and the United Kingdom. Data were collected on clinical OA at any site (hand, knee or hip), based on the clinical classification criteria developed by the American College of Rheumatology (ACR). Frailty was defined according to Fried's criteria. The covariates considered were age, gender, educational level, obesity and country. We used multinomial logistic regression to analyse the associations between OA, frailty/pre-frailty and other covariates. The overall prevalence of clinical OA at any site was 30.4 % (95 % CI:28.6-32.2); frailty was present in 10.2 % (95 % CI:9.0-11.4) and pre-frailty in 51.0 % (95 % CI:49.0-53.0). The odds of frailty was 2.96 (95 % CI:2.11-4.16) and pre-frailty 1.54 (95 % CI:1.24-1.91) as high among OA individuals than those without OA. The association remained when Knee OA, hip OA or hand OA were considered separately, and was stronger in those with increasing number of joints.

Clinical OA is associated with frailty and pre-frailty in older adults in European countries. This association might be considered when designing appropriate intervention strategies for OA management.

The purpose of this study was to determine how bilateral lower limb joint function is altered by the combined effects of osteoarthritis and its treatment by total knee arthroplasty. Lower limb joint work of age-matched healthy, control participants was compared to surgical and non-surgical limb work in individuals who had undergone total knee arthroplasty. Research investigating outcomes following total knee arthroplasty has focussed primarily on the surgical knee, identifying deficits in surgical knee function. The existence of additional lower limb deficits and adjustments made by unaffected joints to complement these deficits, has yet to be examined. Joint moments, power and work were calculated using bilateral lower limb force and kinematic data collected during a step-up to heights of 11.25 and 20 cm. Fifty percent of patients were unable to step onto the 20 cm step. At both step heights, when the surgical limb led the step-up, surgical knee work was less than controls. When the non-surgical limb led, deficits in non-surgical lead knee work were observed. In both cases, lead hip work increased. These findings highlight the importance of including exercises that optimize bilateral knee and hip function in rehabilitation programs used following knee replacement. Clinicians working with this population can use this information to assist in the design of evidenced based treatment programs.

Work done by both surgical and non-surgical knees in a step-up task was lower than that done by healthy controls. This deficit was balanced by increased lead hip extensor work.

Patients undergoing arthroscopic partial meniscectomy (APM) are at increased risk of knee osteoarthritis (OA). Meniscal damage and/or surgery may alter knee joint loading to increase OA risk. We investigated changes in knee joint loading following medial APM surgery, compared with the contra-lateral leg. We estimated indices of knee joint loading (external peak knee adduction moment (KAM), KAM impulse and peak knee flexion moment (KFM)) normalized to body size (i.e., body mass (BM) and height (HT)) using 3D gait analysis in 23 patients (17 men, mean (SD) 46.2 (6.4) years, BMI 25.8 (3.4) kg/m(2)) without radiographic knee OA before and 12 months after medial APM. Static alignment was assessed by radiography and self-reported outcomes by Knee injury and Osteoarthritis Outcome Score (KOOS). Peak KAM and KAM impulse increased in the APM leg compared to the contra-lateral leg from before to 12 months after surgery (change difference: 0.38 Nm/BM*HT% 95% CI 0.01 to 0.76 (P = 0.049) and 0.20 Nm*s/BM*HT% 95% CI 0.10 to 0.30 (P < 0.001)). Patients self-reported improvements on all KOOS subscales (KOOS pain improvement: 22.8 95% CI 14.5 to 31.0 (P < 0.01)).

A relative increase in indices of medial compartment loading was observed in the leg undergoing APM compared with the contra-lateral leg from before to 12 months after surgery. This increase may contribute to the elevated risk of knee OA in these patients. Randomized trials including a non-surgical control group are needed to determine if changes in joint loading following APM are caused by surgery or by changes in symptoms.

The improvement of life expectation in our country explains at least in part the increase of the proportion of the elderly in hospitalized patients. The aim of this study was to identify the main diseases leading to hospitalization of the aged in a rheumatology department, to establish their clinical profiles and to evaluate the quality of their management. Retrospective chart review about the elderly (age > or =65 years) admitted in the rheumatology department of the Charles Nicolle Hospital during a 2-year-period [January 2003-December 2004]. Among the 831 patients admitted to our inpatient clinic during that period, 86 were 65-year-old or more representing 10% of the total. Mean age was 71.2 years [65-88]. The sex ratio was 1/3. A history of a mean of two associated diseases [0-5] was noted. They were dominated by hypertension (50%) and diabetes (26.7%). Almost 1/3 of the elders had a surgical history. Gastro-intestinal troubles have been noted in only 19% of cases. The main cause of hospitalization was a diagnosis exploration (77.6%). The remainings were admitted for therapeutic adjustment. The disease was evolving since in mean 16 months (15 days-15 years). The mean duration of hospitalization was 21.2 days (4-60). The pathologies involved were varied dominated by degenerative rheumatisms (26.7%) with a predilection to lumbar spine, systemic diseases: 18 cases (20.9%) with 13 cases of rheumatoid arthritis, and malignant bone diseases (18.7%). At least two rheumatic diseases were found together in 49 patients (57%). The clinical findings were atypical in almost half cases (42.4%) in such aged patients. Besides drugs prescribed for non rheumatic diseases, our patients took a mean of 3.4 drugs (1-8) as symptomatic, adjuvant or etiologic treatment. The treatment observance was good in 74.4% of cases. Iatrogenic incidents occurred in 14 cases (16.2%). The outcome was favorable in 68.9% of cases. Twelve of our patients necessitated a third help. Half of our patients (54%) were controlled in our outpatient clinic 1-2 months after their issue, 12 have been hospitalized for the same disease, 8 deceased, and 19 have been lost.

The management of the elderly patients in hospitalization must be multidisciplinary. It should take into account the clinical and therapeutic particularities of such a population. Prevention remains the best guarantee for a good quality of life and to decrease social and economic costs.

We undertook this study to develop a grading scale to assess knee osteoarthritis using the Bristol Score. Between August and November 2004, a clinimetrical, prospective, group-controlled, observational, cross-sectional and analytical study was done. The study sample was comprised of 55 patients, 35 years old and over, with clinical-radiographic diagnosis of knee osteoarthritis following the American Academy of Rheumatology criteria. The Bristol Score was used in 25 patients by two standardized orthopedic surgeons. Sensitivity, consistency and validity of the Bristol Score were determined. The new grading scale to assess osteoarthritis Magdalena de las Salinas H-1(MSH1) was used in 30 patients. Sensitivity, consistency and validity of the MSH1 were also determined. Both indexes were compared in these terms. An osteoarthritis radiographic score was developed to assess the validity of the MSH1. Inter-observer intraclass correlation coefficient (ICC) for the Bristol Score in its categories was total 0.62, function 0.84, pain 0.40 and movement 0.89. Inter-observer ICC for MSH1 in its categories was total 0.91, function 0.92, pain 0.79 and movement 0.86 (p <0.0001). Inter-observer weighed kappa of the Bristol Score was 0.51 (p = 0.002), with 80% agreement. The weighed kappa for the MSH1 was 0.81 (p <0.0001) with 90% agreement. Correlation between the Bristol Score and the osteoarthritis radiographic score was -0.29 (p = 0.049). Correlation between the MSH1 and the radiographic score of osteoarthritis was -0.62 (p <0.01).

MSH1 achieved better validity than the Bristol Score and can be considered a reliable instrument to assess knee osteoarthritis.

Total hip arthroplasty (THA) offers an effective method of pain relief and restoration of function for patients with end-stage arthritis. The anterior approach (AA) claims to benefit patients with decreased pain, increased mobilisation and decreasing length of hospital stay (LOS). In a socialised healthcare platform we questioned whether the AA, compared to posterior (PA) and lateral (LA) approaches, can decrease the cost burden. Using a retrospective matched cohort study, we matched 69 AA patients to 69 LA and 69 PA patients for age ( Using the RIW based cost analysis and 2-day reduction (95% CI 1.8-2.4) in LOS, the AA offers an estimated savings per case of $4099 (

The AA THA provides statistically significant reductions in cost compared to PA and LA while releasing rehabilitation resources.

Systemic lupus erythematosus (SLE) is a heterogenous autoimmune disease, which can affect different organs. Increased proportions of CD4⁺CD25-Foxp3⁺ T cells have been described in SLE patients. The exact role of this cell population in SLE patients still remains unclear. We therefore analyzed this T cell subset in a large cohort of SLE patients with different organ manifestations. Phenotypic analyses, proportions and absolute cell numbers of CD4⁺CD25-Foxp3⁺ T cells were determined by flow cytometry (FACS) in healthy controls (HC) (n = 36) and SLE patients (n = 61) with different organ manifestations. CD4⁺CD25⁻Foxp3⁺ T cells were correlated with clinical data, the immunosuppressive therapy and different disease activity indices. In patients with active glomerulonephritis, CD4⁺CD25⁻Foxp3⁺ T cells were analyzed in urine sediment samples. Time course analyses of CD4⁺CD25⁻Foxp3⁺ T cells were performed in patients with active disease activity before and after treatment with cyclophosphamide and prednisone. CD4⁺CD25⁻Foxp3⁺ T cells were significantly increased in active SLE patients and the majority expressed Helios. Detailed analysis of this patient cohort revealed increased proportions of CD4⁺CD25⁻Foxp3⁺ T cells in SLE patients with renal involvement. CD4⁺CD25⁻Foxp3⁺ T cells were also detected in urine sediment samples of patients with active glomerulonephritis and correlated with the extent of proteinuria.

CD4⁺CD25⁻Foxp3⁺ T cells resemble regulatory rather than activated T cells. Comparative analysis of CD4⁺CD25⁻Foxp3⁺ T cells in SLE patients revealed a significant association of this newly described cell population with active nephritis. Therefore CD4⁺CD25⁻Foxp3⁺ T cells might serve as an important tool to recognize and monitor SLE patients with renal involvement.

The purpose of this study was to systematically review the existing literature reporting surgical outcomes of simultaneous high tibial osteotomy (HTO) and anterior cruciate ligament reconstruction (ACLR) in anterior cruciate ligament deficient (ACLD) knees. This study was conducted per the methods of the Cochrane Handbook for Systematic Reviews of Intervention, with findings reported per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The electronic databases MEDLINE, EMBASE, and PubMed were searched for relevant studies and pertinent data was extracted. Studies reporting post-operative outcomes following simultaneous HTO and ACLR in ACLD knees were included. The search identified 515 studies, of which 18 (n = 516) were included. The mean MINORS scores for non-comparative and comparative studies were 11.6 ± 1.34 and 17.3 ± 1.9, respectively. Simultaneous HTO and ACLR resulted in improved functional subjective patient outcomes across a variety of scales. Simultaneous HTO and ACLR was effective in correcting varus angulation, with the post-operative mechanical angle ranging from 0.3° valgus to 7.7° valgus. The reported complication rate ranged from 0 to 23.5%. Across six studies, a total of 13 (6.5%) patients required revision HTO; while across four studies, 20 (17.5%) patients had failure of the ACL graft, with one receiving revision ACLR. IV.

Combined HTO and ACLR may be indicated in patients with ACLD knees with varus angulation. This systematic review found that the combined surgery resulted in significant improvement in post-operative functional subjective outcomes. However, it remains unclear if HTO with ACLR is superior to ALCR or HTO alone due to the lack of comparative studies. Overall, HTO with ACLR was found to have low rates of complications, re-ruptures, and need for revision surgery. This review found that patients continued to have progression of OA despite combined HTO with ACLR. Future research is required to better understand the effects of combined HTO and ACLR compared to ACLR or HTO alone and to evaluate the long-term post-operative progression of medial compartment OA following combined HTO and ACLR.

International rheumatology guidelines advocate a treat to serum urate target (T2T) approach for gout management. While individual studies have reported regional and national-level gout management, global patterns in gout care have not been synthesized. This study aimed to systematically review and meta-analyze global T2T care for patients with gout. Electronic databases were searched for studies reporting medication and serum urate testing in patients with gout. Meta-analyses were conducted to determine the pooled proportion of patients with gout achieving pre-specified T2T indicators. Sixty-seven papers were included from North America (n = 31 studies), Europe (n = 22), Oceania (n = 7), Asia (n = 6), and reporting data from multiple continents (n = 1). The global pooled percentages (95% confidence interval (CI)) of patients with gout achieving T2T indicators were: 52% (45%, 59%) on urate lowering therapy (ULT), 50% (40%, 61%) on ULT receiving regular uninterrupted ULT, 53% (40%, 65%) on ULT having any serum urate testing, and 34% (28%, 41%) on ULT achieving a serum urate target.

Outside North America and Europe, there are relatively few studies about T2T care for gout management. However, available data demonstrate that a minority of people with gout receive T2T care worldwide. For those prescribed ULT, there are low rates of continuous therapy, serum urate testing, and achievement of serum urate target.

Psoriasis is an important clinical feature in spondyloarthritis. However, the influence of psoriasis on the clinical, functional and imaging features of patients with inflammatory back pain (IBP) related to spondyloarthritis is not known. To determine the prevalence of psoriasis and its impact in patients with recent IBP suggestive of spondyloarthritis. The prevalence of psoriasis was determined in 692 patients (mean age 33.3±8.5 years, 53.8% female, 58.3% human leucocyte antigen B27 positive) included in the DESIR cohort. Demographic characteristics, imaging features and blood tests of patients with and without psoriasis were compared. The prevalence of psoriasis was 16.6%. Patients with rather than without psoriasis more often presented with enthesitis (59.1% vs 47.5%; p=0.02) and had more active disease (BASDAI 4.8±1.8 vs 4.4±2.0; p=0.05) and poorer functional status (BASFI 3.6±2.2 vs 3.0±2.3; p=0.006; SF-36 (physical function) 61.9±24.4 vs 66.9±24.9; p=0.04). Patients with psoriasis showed higher levels of C-reactive protein (p=0.02), total cholesterol (p=0.01) and triglycerides (p=0.02). The two groups did not differ in structural changes as assessed by standard x-rays or MRI at the spinal and sacroiliac levels. However, ultrasonography of the Achilles tendon revealed psoriasis associated with bone erosions (p=0.0003) and abnormal vascularisation (p=0.04). Multivariate regression analysis revealed BASFI score (p=0.03), cholesterol level (p=0.02), dactylitis (p=0.0006) and family history of psoriasis (p<0.0001) as independent predictors of psoriasis.

In patients with recent IBP suggestive of spondyloarthritis, psoriasis is associated with active axial disease and frequent concomitant enthesopathy and dactylitis.

The choice of surgical approach for THA remains controversial. Some studies suggest that the direct anterior approach (DAA) leads to less muscle damage than the miniposterior approach (MPA), but there is little high-quality evidence indicating whether this accelerates recovery, or whether this approach-which may be technically more demanding-is associated with component malposition or more complications. (1) Does the DAA result in faster return to activities of daily living than the MPA? (2) Does the DAA have superior patient-reported outcome measures than the MPA? (3) Does the DAA result in improved radiographic outcomes than the MPA? (4) Does the DAA have a higher risk of complications than the MPA? Between March 1, 2013, and May 31, 2016, 116 patients undergoing primary unilateral THA were randomized to either the DAA or MPA; 15 patients withdrew after randomization, and one died 6 months after surgery from a stroke unrelated to the procedure. Recruitment stopped when 52 patients had been randomized into the DAA group and 49 in the MPA group (n = 101). After patient randomization, one high-volume surgeon performed all of the DAAs and three high-volume surgeons performed the MPA THAs. The groups did not differ in age (65 years; SD 11; range, 38-86 years), sex (52% women), or body mass index (mean 29 kg/m; SD 6 kg/m; range, 21-40 kg/m; all p > 0.40). Functional results included time to discontinue gait aids, discontinue all narcotics, and independence with various activities of daily living; accelerometer data evaluated activity level. Clinical and radiographic outcomes, Hip disability and Osteoarthritis Outcome Score, SF-12, and Harris hip scores to 1 year were also tabulated. The minimum followup was 365 days (mean ± SD, 627 ± 369 days). There were slight differences in early functional recovery that favored the DAA versus the MPA: time to discontinue walker use (10 versus 15 days, p = 0.01) and time to discontinue all gait aids (17 versus 24 days, p = 0.04). There were no other differences in early functional milestones, although at 2 weeks after surgery, mean steps per day were 3897 (SD 2258; range, 737-11,010) for the DAA versus 2235 for the MPA (SD 1688; range, 27-7450; p < 0.01). There was no difference in activity monitoring at 1 year. There were no differences in patient-reported outcome scores between the groups. There was no difference in the radiographic parameters measured in the two groups, including leg length discrepancy, component position, or offset, and there was no subsidence observed in any hip. There was no difference in complications between the DAA and the MPA groups (8% [four of 52] versus 10% [five of 49]; p = 0.33). Level I, therapeutic study.

Both the DAA and MPA approaches provided excellent early recovery with a low risk of complications. Patients undergoing the DAA had a slightly faster recovery, as measured by milestones of function and quantified by activity monitor data, but no substantive differences were evident at 2 months. Because the DAA is the less studied approach, longer term (> 1 year) complications may yet accrue, will be important to quantify, and may offset early benefits.

Rheumatoid arthritis (RA) is characterized by synovial lining hyperplasia, in which there may be an imbalance between the growth and death of fibroblast-like synoviocytes (FLSs). Antibodies against citrullinated proteins are proposed to induce RA. This study aimed to investigate the pathogenic role of citrullinated fibronectin (cFn) in RA. The distribution of fibronectin (Fn) and cFn in synovial tissues from RA and osteoarthritis (OA) patients was examined by immunohistochemical and double immunofluorescence analysis. FLSs were isolated from RA and OA patients and treated with Fn or cFn. Apoptosis was detected by flow cytometry and TUNEL assay. The expression of survivin, caspase-3, cyclin-B1, Bcl-2 and Bax was detected by real-time PCR. The secretion of proinflammatory cytokines was measured by ELISA. Fn formed extracellular aggregates that were specifically citrullinated in synovial tissues of RA patients, but no Fn deposits were observed in those of OA patients. Fn induced the apoptosis of RA and OA FLSs while cFn inhibited the apoptosis of RA and OA FLSs. Fn significantly increased the expression of caspase-3 and decreased the expression of survivin and cyclin-B1 in FLSs from RA and OA patients. cFn significantly increased the expression of survivin in RA FLSs. Furthermore, cFn increased the secretion of TNF-α and IL-1 by FLSs.

cFn plays a potential pathophysiologic role in RA by inhibiting apoptosis and increasing proinflammatory cytokine secretion of FLSs.

Mesenchymal stem cells (MSCs) have immunosuppressive activity and can differentiate into bone and cartilage; and thus seem ideal for treatment of rheumatoid arthritis (RA). Here, we investigated the osteogenesis and chondrogenesis potentials of MSCs seeded onto nano-fiber scaffolds (NFs) in vitro and possible use for the repair of RA-affected joints. MSCs derived from healthy donors and patients with RA or osteoarthritis (OA) were seeded on poly-lactic-glycolic acid (PLGA) electrospun NFs and cultured in vitro. Healthy donor-derived MSCs seeded onto NFs stained positive with von Kossa at Day 14 post-stimulation for osteoblast differentiation. Similarly, MSCs stained positive with Safranin O at Day 14 post-stimulation for chondrocyte differentiation. Surprisingly, even cultured without any stimulation, MSCs expressed RUNX2 and SOX9 (master regulators of bone and cartilage differentiation) at Day 7. Moreover, MSCs stained positive for osteocalcin, a bone marker, and simultaneously also with Safranin O at Day 14. On Day 28, the cell morphology changed from a spindle-like to an osteocyte-like appearance with processes, along with the expression of dentin matrix protein-1 (DMP-1) and matrix extracellular phosphoglycoprotein (MEPE), suggesting possible differentiation of MSCs into osteocytes. Calcification was observed on Day 56. Expression of osteoblast and chondrocyte differentiation markers was also noted in MSCs derived from RA or OA patients seeded on NFs. Lactic acid present in NFs potentially induced MSC differentiation into osteoblasts.

Our PLGA scaffold NFs induced MSC differentiation into bone and cartilage. NFs induction process resembled the procedure of endochondral ossification. This finding indicates that the combination of MSCs and NFs is a promising therapeutic technique for the repair of RA or OA joints affected by bone and cartilage destruction.

Activation of osteoclastogenesis at the bone site in rheumatoid arthritis (RA) is well established. The mechanisms by which circulating osteoclast precursors contribute are still unclear. Peroxisome proliferator-activated receptor γ coactivator 1β (PGC-1β) is implicated in transcriptional regulation of osteoclastogenesis in mouse models. This study was undertaken to investigate the contribution of PGC-1β to circulating osteoclast precursors and its link to bone destruction in RA. PGC-1β expression in RA peripheral blood CD14+ monocytes was increased and showed correlation with joint destruction shown on radiographs. Cells from RA patients or healthy controls were transfected with a lentivirus vector for PGC-1β gene silencing or overexpression and cultured with macrophage colony-stimulating factor and RANKL. Bone resorption activity, bone-degrading enzymes, and signaling molecules were measured in these mature osteoclasts. Increased nuclear accumulation of PGC-1β was observed in RA peripheral blood CD14+ monocytes, and these cells had stronger osteoclastogenesis than in healthy controls. PGC-1β protein expression was positively correlated with radiographic joint destruction (r = 0.396-0.413; all P < 0.05). PGC-1β knockdown suppressed (51-82% reduction) the expression of cathepsin K, tartrate-resistant acid phosphatase (TRAP), and matrix metalloproteinase 9 (MMP-9), as well as osteoclast differentiation and bone resorption activity. Conversely, PGC-1β overexpression increased these markers (by 1.5-1.8-fold) and osteoclastogenesis. VIVIT, an inhibitor of NFATc1 activation, inhibited the effect of overexpressed PGC-1β by reducing cathepsin K, TRAP, and MMP-9 expression. Chromatin immunoprecipitation assay and dual-luciferase reporter gene assay showed PGC-1β bound to NFATc1 promoter, leading to transcriptional activation.

Activation of the PGC-1β/NFATc1 pathway in circulating osteoclast precursors was associated with bone destruction in RA. This may represent a new treatment target.

Femoral stems with exchangeable (modular) necks were introduced to offer surgeons an increased choice when determining the version, offset and length of the femoral neck during total hip arthroplasty (THA). It was hoped that this would improve outcomes and reduce complications, particularly dislocation. In 2010, the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) first reported an increased rate of revision after primary THA using femoral stems with an exchangeable neck. The aim of this study was to provide a more comprehensive up-to-date analysis of primary THA using femoral stems with exchangeable and fixed necks. The data included all primary THA procedures performed for osteoarthritis (OA), reported to the AOANJRR between 01 September 1999 and 31 December 2014. There were 9289 femoral stems with an exchangeable neck and 253 165 femoral stems with a fixed neck. The characteristics of the patients and prostheses including the bearing surface and stem/neck metal combinations were examined using Cox proportional hazard ratios (HRs) and Kaplan-Meier estimates of survivorship. It was found that prostheses with an exchangeable neck had a higher rate of revision and this was evident regardless of the bearing surface or the size of the femoral head. Exchangeable neck prostheses with a titanium stem and a cobalt-chromium neck had a significantly higher rate of revision compared with titanium stem/titanium neck combinations (HR 1.83, 95% confidence interval 1.49 to 2.23, p < 0.001). Revisions were higher for these combinations compared with femoral stems with a fixed neck.

There appears to be little evidence to support the continued use of prostheses with an exchangeable neck in primary THA undertaken for OA. Cite this article:

To assess compliance rates with the current Canadian osteoporosis guidelines and whether the Fracture Risk Assessment Tool score in patients with rheumatoid arthritis correlated with the likelihood of receiving osteoporosis treatment and having a bone mineral density test. Charts of serial outpatients with rheumatoid arthritis were reviewed to collect bone mineral density test data and patients' use of calcium, vitamin D, and osteoporosis treatment. Odds ratios (OR) were calculated to determine if a higher Fracture Risk Assessment Tool score increased the likelihood of osteoporosis treatment or having a bone mineral density test. Using the Fracture Risk Assessment Tool, the 10-year risk of major osteoporotic fracture was high in 92 (12.5%), moderate in 216 (29.3%), and low in 429 (58.2%) patients. Compared to those at low risk, patients identified as high risk were more likely to receive osteoporosis treatment (OR 16.31, 95% CI 9.45-28.13, P<0.001); calcium (OR 3.89, 95% CI 2.43-6.25, P<0.001); vitamin D (OR 3.46, 95% CI 2.12-5.64, P<0.001); and to have had a bone mineral density test (OR 10.22, 95% CI 5.50-18.96, P<0.001). Among 124 patients currently taking prednisone, half (46.8%) were prescribed a bisphosphonate.

Although compliance with current osteoporosis guidelines remains low among all patients with rheumatoid arthritis, higher risk patients were more likely to have a bone mineral density test and receive treatment for osteoporosis, as indicated by the clear dose response seen along the 10-year fracture risk from low to high-risk groups.

Public and patient involvement is increasingly becoming an expectation of research funders and policy makers. Not all areas of health research are public-facing. Here, we outline an approach for building the skills and developing the relationships required for downstream public and patient involvement in pre-clinical adolescent rheumatology research. To design a methodology for improving researcher-adolescent communications specifically aimed at mutual relationship building for PPI. Deliberate and effective preparation in advance of research involvement to improve the downstream success of that involvement. A research seminar and research skills workshop conducted entirely in 'plain English' for adolescents and their siblings aged 10-20. Upskilling of pre-clinical researchers for effective public involvement. Study co-design between the voluntary charity Irish Children's Arthritis Network and the academic research centre UCD Centre for Arthritis Research. Fifteen adolescents aged 10-20 years old living with arthritis, four pre-clinical researchers and one qualitative researcher investigating adolescent or paediatric arthritis. Relationship building and communications for effective downstream public involvement in pre-clinical and laboratory research. The methodology outlined here was received extremely positively. Both researchers and adolescents living with arthritis felt more comfortable communicating, more knowledgeable about juvenile arthritis and research, and more able to engage in co-operative dialogue. Engaging early, considering the needs of the community and developing appropriate involvement methodology can enable involvement in pre-clinical research.

Dedicating resources to building relationships and skills necessary for co-operative research involvement can overcome some of the barriers to public involvement in pre-clinical and laboratory-based research.

A double-blind randomized multicentric study was performed to test the hypothesis that the analgesic effect of paracetamol-cafeine is equivalent to that of paracetamol-dextropropoxyphen in patients suffering from pain due to osteoarthritis of the spine. Rhumatologists included 124 patients who were randomized into two groups of 62 each. Pain was measured daily during the seven-day treatment Huskisson's Analog Visual Scales; 112 were per protocol and evaluable. The two treatment groups were statistically similar for demographics, vital signs, medical and treatment history. A majority of them had pain located at the lumbar spine only; the other patients had either pain at the cervical or dorsal spine or at several sites. At the end of the week there was a major reduction in pain level: 51.2% in patients given paracetamol-cafeine and 47.0% in those given paracetamol-dextropropoxyphen. The main criteria of efficacy--the percentage of success (decrease of pain > 50%)--was similar in the two groups as well in the intention-to-treat population (p = 0.01) as the per protocol population (p = 0.028). Kinetics of pain decrease during the first day of treatment were assessed with an hourly evaluation during the six first hours and at the 12th hour. There was no difference between the two groups. There was no serious adverse event and the frequency and intensity of the adverse events were similar in the two groups.

The potentializing action of cafeine on paracetamol-induced pain relief enables a degree of pain relief equivalent to that of a combination using an analgesic with a peripheral action, paracetamol, and another with a central action, dextropoxyphen. The fact that the paracetamol-cafeine combination does not have a central action avoids secondary effects induced by central analgesics (drowsiness, constipation) in patients with osteoarthritis back pain.

To determine whether foot structure varies according to the presence and radiographic severity of first metatarsophalangeal (MTP) joint osteoarthritis (OA). Weight-bearing dorsiplantar and lateral radiographs were obtained for the symptomatic foot of 185 participants (105 women, ages 22-85 years) with clinically diagnosed first MTP joint OA. A validated atlas was used to classify participants as having radiographic first MTP joint OA and to stratify into 3 categories of severity (none/mild, moderate, severe). Bone length and width and angular measures of the forefoot and medial arch were performed on radiographs, and differences between categories were compared using univariate general linear models, adjusting for confounders. A total of 150 participants were categorized as having radiographic first MTP joint OA, and participants were further stratified into none/mild (n = 35), moderate (n = 69), or severe (n = 81) OA categories. Participants with radiographically defined first MTP joint OA displayed a greater hallux abductus interphalangeal angle. Greater radiographic severity of first MTP joint OA was associated with a larger hallux abductus interphalangeal angle, a wider first metatarsal and proximal phalanx, and a smaller intermetatarsal angle. No differences in medial arch measurements were observed between the categories.

First ray alignment and morphology differed according to the presence and severity of first MTP joint OA. Prospective studies are required to determine whether the observed differences are a cause or consequence of OA.

Among various lupus renal vascular changes, thrombotic microangiopathy (TMA) presented with the most severe clinical manifestations and high mortality. The pathogenesis of TMA in systemic lupus erythematosus (SLE) was complicated. The aim of this study was to assess clinical manifestations, laboratory characteristics, pathological features and risk factors for clinical outcomes of lupus nephritis patients co-existing with renal TMA in a large cohort in China. Clinical and renal histopathological data of 148 patients with biopsy-proven lupus nephritis were retrospectively analyzed. Serum complement factor H, A Disintegrin and Metalloprotease with Thrombospondin type I repeats 13 (ADAMTS-13) activity, antiphospholipid antibodies and C4d deposition on renal vessels were further detected and analyzed. In the 148 patients with lupus nephritis, 36 patients were diagnosed as co-existing with renal TMA based on pathological diagnosis. Among the 36 TMA patients, their clinical diagnoses of renal TMA were as followings: 2 patients combining with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome, 2 patients combining with anti-phospholipid syndrome, 2 patients with malignant hypertension, 1 patient with scleroderma and the other 29 patients presenting with isolated renal TMA. Compared with the non-renal TMA group, patients with renal TMA had significantly higher urine protein (7.09±4.64 vs. 4.75±3.13 g/24h, P=0.007) and serum creatinine (159, 86 to 215 vs. 81, 68 to 112 μmol/l, P<0.001), higher scores of total activity indices (AI) (P<0.001), endocapillary hypercellularity (P<0.001), subendothelial hyaline deposits (P=0.003), interstitial inflammation (P=0.005), glomerular leukocyte infiltration (P=0.006), total chronicity indices (CI) (P=0.033), tubular atrophy (P=0.004) and interstitial fibrosis (P=0.018). Patients with renal TMA presented with poorer renal outcome (P=0.005) compared with the non-TMA group. Renal TMA (hazard ratio (HR): 2.772, 95% confidence interval: 1.009 to 7.617, P=0.048) was an independent risk factor for renal outcome in patients with lupus nephritis. The renal outcome was poorer for those with both C4d deposition and decreased serum complement factor H in the TMA group (P=0.007).

There were various causes of renal TMA in lupus nephritis. Complement over-activation via both classical and alternative pathways might play an important role in the pathogenesis of renal TMA in lupus nephritis.

To analyse the durability of the responses after haematopoietic stem cell transplantation (HSCT) for severe systemic sclerosis (SSc) and determine whether the high transplant related mortality (TRM) improved with experience. This EBMT/EULAR report describes the longer outcome of patients originally described in addition to newly recruited cases. Only patients with SSc, treated by HSCT in European phase I-II studies from 1996 up to 2002, with more than 6 months of follow up were included. Transplant regimens were according to the international consensus statements. Repeated evaluations analysed complete, partial, or non-response and the probability of disease progression and survival after HSCT (Kaplan-Meier). Given as median (range). Among 57 patients aged 40 (9.1-68.7) years the skin scores improved at 6 (n = 37 patients), 12 (n = 30), 24 (n = 19), and 36 (n = 10) months after HSCT (p<0.005). After 22.9 (4.5-81.1) months, partial (n = 32) or complete response (n = 14) was seen in 92% and non-response in 8% (n = 4) of 50 observed cases. 35% of the patients with initial partial (n = 13/32) or complete response (n = 3/14) relapsed within 10 (2.2-48.7) months after HSCT. The TRM was 8.7% (n = 5/57). Deaths related to progression accounted for 14% (n = 8/57) of the 23% (n = 13/57) total mortality rate. At 5 years, progression probability was 48% (95% CI 28 to 68) and the projected survival was 72% (95% CI 59 to 75).

This EBMT/EULAR report showed that response in two thirds of the patients after HSCT was durable with an acceptable TRM. Based on these results prospective, randomised trials are proceeding.

The patient perspective workshops at the Outcome Measures in Rheumatology Clinical Trials have included daily measures of health status (patient diary) and use of electronic tools for data collection in the research agenda. The objective of this study was to compare daily and weekly registrations of self-reported health status measures between personal digital assistant (PDA) and paper-pencil (PP) format regarding scores, variation, and feasibility. Thirty-eight patients with stable rheumatoid arthritis recorded their health status during 84 days in a repeated crossover design, using PDA or PP format during four 21-day periods. Visual analog scales (VAS) for pain, fatigue, and global disease and the Rheumatoid Arthritis Disease Activity Index were scored daily; the Short Form 36 and Modified Health Assessment Questionnaire were scored weekly. The average scores and measures of variation of the 4 daily health status measures over 21 days did not differ significantly between PDA and PP formats in either of the 2 crossover periods. The values for the average range between the maximum and minimum values for daily measures were similar between the 2 formats, but showed considerable variation (e.g., range for pain VAS was 19-28 mm over each 21-day period). The time to complete the instruments was similar between the 2 formats. Missing daily data entries were generally low for both periods and somewhat higher for PDA. The majority of patients (82.9%) preferred using PDA.

Daily assessments with PDA may be efficiently used for frequent data collection because this format performs similarly to the traditional PP format.

Methotrexate has been implicated in a variety of lung complications, one of which is hypersensitivity pneumonitis. Hypersensitivity pneumonitis most often occurs within the first year of starting low-dose orally administered methotrexate. We present a case of methotrexate-induced hypersensitivity pneumonitis after 30 years of methotrexate use, which is the first case to be reported so far. A 77-year-old African American woman with a history of rheumatoid arthritis presented with progressively worsening shortness of breath and nonproductive cough. She was on a daily dose of 2.5 mg of methotrexate that had been orally administered for the last 30 years. A physical examination was significant for fever of 38.2 °C (100.8 °F), tachycardia, bilateral basal crackles, and oxygen saturation of 88% on room air. A laboratory work up was significant for normal white blood cell count, increased eosinophil count of 18.3%, and erythrocyte sedimentation rate of 111 mm/hour. Sputum cultures were negative for any bacterial pathogens including acid-fast bacilli. Influenza and respiratory syncytial viral infection were ruled out. A (1-3)-B-D-glucan assay (Fungitell®) was within normal limits. Pulmonary embolism was ruled out and echocardiography was normal. A chest X-ray showed hazy opacity with prominent reticulation within the upper lung fields bilaterally, right greater than the left with no pleural effusion. Lung computed tomography revealed nonspecific bilateral upper lung opacification. A pulmonary function test was significant for no obstruction, normal maximum voluntary ventilation, and no restriction, with mildly decreased diffusion. Methotrexate was stopped, and our patient was started on prednisone 60 mg orally administered daily with dramatic clinical and radiologic improvement.

Methotrexate-induced hypersensitivity pneumonitis usually occurs in the initial few weeks to months of starting treatment with methotrexate; however, it can occur late during therapy too, and prompt diagnosis is crucial as it is a reversible condition when diagnosed early.

To assess reliability and construct validity of the Kellgren-Lawrence (K&L) scale in posttraumatic ankle osteoarthritis (OA); additionally evaluate the validity of including tibiotalar tilting in the scale. One-hundred and fifty ankle radiographs (75 patients, unilateral malleolar fractures) evaluated at average of 18 years after surgery. American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot (HF) score and pain (visual analog scale) were recorded. Grading of OA according to K&L criteria and identification of OA features was performed on standardized radiographs by four physicians. Minimal joint space width, sclerosis, and talar tilt angle were quantified by digital measurements. A modified K&L scale including talar tilting is presented. Validity of original and modified scale was evaluated and expressed as ability to (1) Identify those with clinical symptoms of ankle OA; and (2) Distinguish between different degrees of fracture severity. Inter- and intra-observer reliability of OA assessment according to K&L were good (ICC 0.61 and 0.75). Original and modified K&L grades significantly increased with decreasing AOFAS ankle-HF scores and greater pain. A talar-tilt angle > 2° compared with ≤ 2° in grade 3 was associated with significantly higher pain levels (VAS pain 4.2 vs 1.4, respectively; mean difference 2.8, 95% CI 0.5-5.1). More severe fracture patterns at time of surgery were more often in patients with the highest K&L grades.

The K&L scale is a valid and reliable radiographic grading system for assessment of ankle OA. Inclusion of the talar tilt angle might allow for better differentiation with respect to clinical outcomes.

Noninfectious aortitis may occur in the context of a recognized systemic disease or as a topographically limited lesion without systemic features, which is called clinically isolated aortitis (CIA). This study was undertaken to better define and stress the limitations of this diagnostic category in a large population of patients in a single center dedicated to aortic diseases and to suggest recommendations for care. Records of patients undergoing thoracic aortic surgery (1996-2012) at the Cleveland Clinic were reviewed to identify 196 patients with histopathologically proven aortitis. Clinical diagnoses (giant cell arteritis [GCA], Takayasu arteritis [TAK], CIA, or Other) were determined at the time of surgery. Clinical features, laboratory findings, and imaging results were recorded throughout the follow-up period. At least 6 months of follow-up data were available for 73 CIA patients. The mean age of the patients at time of surgery was 65.6 years (range 15-88 years); 67% of patients were female, and 90.3% were white. At the time of surgery, 129 patients (65.8%) met criteria for CIA, 42 (21.4%) for GCA, 14 (7.1%) for TAK, and 11 (5.6%) met criteria for other systemic inflammatory diseases. During a mean follow-up period of 56.2 months, 19% of CIA patients developed new symptoms, 45% developed new radiographic vascular lesions, 40% underwent additional vascular surgery, and 12% died (n = 9). Eleven of 73 patients (15%) initially classified as having CIA developed features of a systemic disease, most often GCA.

The majority of patients (66%) with histopathologically proven aortitis have CIA at the time of surgery. CIA patients infrequently report new symptoms over time, but new vascular lesions requiring surgery commonly occur. Serial follow-up including large vessel imaging is strongly advised for all aortitis patients.

Treatment response in randomized clinical trials (RCT) of osteoarthritis (OA) has been assessed by multiple primary and secondary outcomes, including pain, function, patient and clinician global measures of status and response to treatment, and various composite and responder measures. Identifying outcome measures with greater responsiveness to treatment is important to increase the assay sensitivity of RCTs. To assess and compare the responsiveness of different outcome measures used in placebo-controlled RCTs of OA. The Resource for Evaluating Procedures and Outcomes of Randomized Trials database includes placebo-controlled clinical trials of pharmacologic treatments (oral, topical, or transdermal) for OA identified from a systematic literature search of RCTs published or publicly available before August 5, 2009, which was conducted using PubMed, the Cochrane collaboration, publicly-available websites, and reference lists of retrieved publications. Data collected included: (1) pain assessed with single-item ratings and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale; (2) patient and clinician global measures of status, improvement, and treatment response; (3) function assessed by the WOMAC function subscale; (4) stiffness assessed by the WOMAC stiffness subscale; and (5) the WOMAC and Lequesne Algofunctional Index composite outcomes. Measures were grouped according to the total number of response categories (i.e., <10 categories or ≥10 categories). The treatment effect (difference in mean change from baseline between the placebo and active therapy arms) and standardized effect size (SES) were estimated for each measure in a meta-analysis using a random effects model. There were 125 RCTs with data to compute the treatment effect for at least one measure; the majority evaluated non-steroidal anti-inflammatory drugs (NSAIDs), followed by opioids, glucosamine and/or chondroitin, and acetaminophen. In general, the patient-reported pain outcome measures had comparable responsiveness to treatment as shown by the estimates of treatment effects and SES. Treatment effects and SESs were generally higher for patient-reported global measures compared with clinician-rated global measures but generally similar for the WOMAC and Lequesne composite measures.

Comparing different outcome measures using meta-analysis and selecting those that have the greatest ability to identify efficacious treatments may increase the efficiency of clinical trials of treatments for OA. Improvements in the quality of the reporting of clinical trial results are needed to facilitate meta-analyses to evaluate the responsiveness of outcome measures and to also address other issues related to assay sensitivity.

To investigate the effect of 1-year treatment with the anti-tumor necrosis factor-α (TNF-α) drug etanercept on lipid profile and oxidative stress in children and adolescents with juvenile idiopathic arthritis (JIA). Thirty children with JIA (22 females; mean age 12.3 ± SD 5.7 yrs), all eligible for anti-TNF-α treatment, were assessed at baseline and after 6- and 12-month treatment with etanercept. Disease activity was determined using the Juvenile Arthritis Disease Activity Score (JADAS). Blood samples were drawn to measure the acute-phase reactants C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), lipids, and the proinflammatory cytokines TNF-α, interleukin-1β (IL-1β), IL-6 and interferon-γ. To measure the oxidative stress marker 8-iso-prostaglandin F2α, 24-h urine samples were collected. Inflammatory indicators (CRP and ESR) and JADAS scores improved significantly after 1 year of etanercept treatment (all p < 0.001). Proinflammatory cytokines showed significant reduction during the study period (all p < 0.001). Similar reductions were detected in total cholesterol (p < 0.001), low-density lipoprotein cholesterol (p = 0.04), and triglycerides (p < 0.001), whereas no significant change was found in high-density lipoprotein cholesterol. No side effects were observed during the treatment period.

This study shows for the first time that anti-TNF-α therapy for JIA is associated not only with a beneficial effect on clinical disease activity and inflammatory indexes, but also with improved lipid profile and oxidative stress. These findings suggest that TNF-α blockers might reduce atherosclerotic risk in children with JIA.

To estimate the prevalence and age-stratified treatment trends and clinical characteristics of rheumatoid arthritis (RA) in Japan. Using 7 RA definitions, the prevalence of RA in those aged ≥16 years was estimated using the National Database of Health Insurance Claims and Specific Health Checkups of Japan in the fiscal year 2017. We analyzed age-stratified trends in characteristics and treatments. Of 1 116 122 patients aged ≥16 years with at least 1 RA-related International Classification of Diseases-10 code, 825.7 thousand patients (women, 76.3%) were assessed as having RA with an estimated prevalence of 0.65%. The highest age-stratified prevalence was 1.63% in patients aged 70-79 years. Overall, 60.8% and 7.0% of patients with RA were aged ≥65 years and ≥85 years, respectively. Methotrexate use was most frequent in patients aged 50-59 years (73.0%) and least frequent in patients aged ≥85 years (38.2%). Biologic disease-modifying antirheumatic drugs use was 50.9% in patients aged 16-19 years and decreased to 13.7% in those aged ≥85 years. Preference for the use of tumor necrosis factor inhibitors versus abatacept decreased from 24.0:1 to 1.7:1 in patients aged 16-19 years and ≥85 years, respectively. The prevalence of cardiovascular disease was 3.5% in patients aged 60-69 years and 12.1% in those aged ≥85 years. Overall RA-related orthopedic surgeries were most prevalent in patients aged 70-79 years.

The estimated prevalence of patients with RA in Japan was 0.65%. Age-stratified treatment trends and clinical characteristics have been described in a super-aged society for the first time.

In our laboratory, we have developed an immunorosette technique for the depletion of T cells from bone marrow transplants. Tetrameric complexes of monoclonal antibodies are able to form very stable immunorosettes, which are efficiently depleted with the aid of a blood cell separator. Major improvements over the original sheep red blood cell depletion are the use of human (patient or donor derived) erythrocytes instead of sheep-derived cells, and the possibility of using a closed system for separation in a cell separator. In contrast to bone marrow, mobilized haematopoietic stem cell transplants obtained after leucocytapheresis contain higher numbers of T cells. Therefore, a different approach is necessary. We have used two CD34 selection systems (Isolex 300SA and the Clinimacs) to perform T-cell depletions from peripheral blood stem cell (PBSC) transplants. Immunorosette T-cell depletion, with CD2/CD3 tetrameric complexes, of bone marrow transplants resulted in a mean 2.5 log depletion of T cells with a yield of 50% of the CD34+ cell population. Stem cell selection of PBSC transplants using one of the CD34 selection procedures resulted in a 4.5 log depiction of T cells for both systems, but with different results for the recovery of CD34+ cells. An increased yield of CD34+ cells was obtained with the Clinimacs procedure (57.9+/-9.0%) in comparison to the Isolex procedure (40.1+/-12.5%).

Our own immunorosette depletion technique and the two tested CD34 selection methods for stem cell transplants both resulted in a very efficient T-cell depletion with the recovery of 40-60% of the CD34 haematopoietic stem cells present in the transplant.

The purpose of this study was to compare functional outcomes, quality of life and survivorship at a minimum of 10 years postoperatively, between MB and AP tibial components in fixed-bearing UKAs. A retrospective cohort study of 146 Query ID="Q3" Text="Author names: Please confirm if the author names are presented accurately and in the correct sequence (Lo Ngai Nung, Yeo Seng Jin). Also, kindly confirm the details in the metadata are correct." UKAs performed between 2004 and 2007 by a single fellowship-trained arthroplasty surgeon was carried out. 27 UKAs received MB tibial components and 119 UKAs received AP tibial components. The cohort was followed up prospectively for 10 years. Functional outcomes were compared using the Knee Society Functional Score (KSFS), Knee Society Knee Score (KSKS) and Oxford Knee Score (OKS). Quality of life measures were obtained from the Physical Component Summary (PCS) and Mental Component Summary (MCS), derived from the Short Form 36 Health Survey (SF-36). Propensity score matching was performed in a 1:3 ratio of MB versus AP tibial components to account for possible confounding variables. Thereafter, outcomes between the two groups were compared. The proportion of patients who had attained the minimum clinically important difference (MCID) for the abovementioned scores was recorded as well. After propensity score matching, there were 28 UKAs with MB tibial components and 76 UKAs with AP tibial components. There was no significant difference between the two groups in functional outcomes (KSFS, KSKS and OKS), quality of life (PCS and MCS) and survivorship (92.3% vs 91.1%, respectively) at a minimum of 10 years postoperatively. However, a significantly higher proportion of patients in the group with AP tibial components attained the MCID for PCS at 10 years postoperatively, compared to those with MB tibial components (p = 0.031). III.

In conclusion, there were no significant differences in functional outcomes measures, quality of life and survivorship between MP and AP tibial components at a minimum of 10 years postoperatively.

The goal of this study was to identify serum markers that are modulated by treatment with golimumab with or without methotrexate (MTX) and are associated with clinical response. Sera were collected at weeks 0 and 4 from a total of 336 patients (training dataset, n = 100; test dataset, n = 236) from the GO-FORWARD study of patients with active rheumatoid arthritis despite MTX. Patients were randomly assigned to receive placebo plus MTX; golimumab, 100 mg plus placebo; golimumab, 50 mg plus MTX; or golimumab, 100 mg plus MTX. Subcutaneous injections were administered every 4 weeks. Samples were tested for select inflammatory, bone, and cartilage markers and for protein profiling using multianalyte profiles. Treatment with golimumab with or without MTX resulted in significant decreases in a variety of serum proteins at week 4 as compared with placebo plus MTX. The American College of Rheumatology (ACR) 20, ACR 50, and Disease Activity Score (DAS) 28 responders showed a distinct biomarker profile compared with nonresponding patients. http://ClinicalTrials.gov identification number: NCT00264550.

ACR 20 and ACR 50 responders among the golimumab/golimumab + MTX-treated patients had a distinct change from baseline to week 4 in serum protein profile as compared with nonresponders. Some of these changed markers were also associated with multiple clinical response measures and improvement in outcome measures in golimumab/golimumab + MTX-treated patients. Although the positive and negative predictive values of the panel of markers were modest, they were stronger than C-reactive protein alone in predicting clinical response to golimumab.

Rheumatoid arthritis (RA) and chronic periodontitis (CP) are the most common chronic inflammatory diseases and have remarkable similar pathologies. The aim of this study is to investigate the impact of periodontal status on oxidative stress in patients with RA by evaluating serum oxidative parameters and prolidase levels. For this cross-sectional comparative study, the following four groups were composed of 20 individuals each (80 individuals total): 1) RA with CP (RA-CP group); 2) RA but periodontally healthy (RA-C group); 3) systemically healthy with CP (CP group); and 4) systemically and periodontally healthy (C group). Demographic, periodontal, rheumatological, and serum oxidative parameters as determined by serum total antioxidant status, total oxidant status, oxidative stress index (OSI), lipid hydroperoxide levels, paraoxonase, arylesterase, and ceruloplasmin activity, prolidase level, and total sulfhydryl groups were evaluated. The OSI values of the RA-CP group were statistically significantly higher than those of the C group (P <0.05). The prolidase levels of the RA-C, RA-CP groups and the CP group were statistically higher than those of the C group (P = 0.001, P = 0.007, and P = 0.001, respectively).

Although CP and RA each increase oxidative stress, in a small sample size these effects are only significant when both CP and RA are combined relative to neither exposure. In addition, increased prolidase levels in patients with RA and CP may be related to increased oxidative tissue damage.

To analyse the use of complementary and alternative medicine (CAM) in children with rheumatic diseases, treated at a paediatric rheumatology centre in Italy. Parents of children with different kinds of chronic rheumatic diseases anonymously completed a questionnaire about their children's past or current use of CAM. Two groups of patients were analysed: Group A consisted of children who were still attending the centre; Group B consisted of children who had not attended the clinic for more than one year. 150 completed surveys were analysed: 22 paediatric patients (14.7%), 10/100 in group A and 12/50 in group B, used CAM to treat their diseases. The therapies used the most were homeopathy, herbal remedies, vitamins and minerals. We observed a significantly greater use of CAM among patients who had not attended the clinic for more than one year (24%) as compared to those who were regularly checked (10%) (p=0.02). Parents' use of CAM was significantly related to its use for their children (p=0.001). A poor outcome, probably related to the exclusive use of alternative treatments, was observed in three out of six patients who had completely stopped using traditional immunosuppressive drugs.

Physicians should be aware of the use of CAM particularly in patients who skip their regular check-ups. The use of CAM to treat childhood rheumatic conditions in Italy seems to be less frequent than in North America.

To describe the translation and test of the Danish version of the original British 'Rheumatoid Arthritis Self-Efficacy Questionnaire' (RASE). The questionnaire was forward and back translated by individuals with Danish and English as their respective primary languages. The questionnaire was tested by five lay-people and in the field by 10 + five persons with rheumatoid arthritis (RA). A test-retest was performed on 62 outpatients with RA. The sensitivity of the adapted Danish version of RASE (RASE-DK) was finally tested on 106 outpatients with RA - before, immediately after and three months after they had participated in a short self-management course performed by a multidisciplinary team. RASE-DK showed good face validity, but 'relaxation' was interpreted in various ways. Internal consistency evaluated by Cronbach's alpha was 0.91. Reliability evaluated by the intra-class correlation coefficient (ICC) was 0.88. A Bland-Altman plot showed good agreement. RASE-DK, like the original English version of RASE, was not associated with disease activity (Disease Activity Score, DAS-28) or disability (Health Assessment Questionnaire, HAQ), and correlated significantly with the Arthritis Self-Efficacy Scale (ASES) subscales 'other' and 'pain', and total ASES. RASE-DK showed a highly significant change, from baseline to immediately after participation in the short course (p < 0.001). The effect faded during the following three months.

RASE-DK met the appropriate standards for validity, reliability and sensitivity, and is appropriate for use in Denmark. However, the concept of self-efficacy may be too abstract for a few individuals, and relaxation is interpreted in various ways by the Danish patients.

To investigate the effectiveness of Kirschner wire fixation in scapholunate joint, capitolunate joint, and lunotriquetral joint combined with bone anchor repair for the treatment of acute perilunate injury. Between January 2007 and January 2012, 35 cases of acute perilunate injury were treated. There were 30 males and 5 females with an average age of 45.5 years (range, 32-56 years). Fractures were caused by falling from height in 18 cases, by traffic accident in 11 cases, and by fall injury in 4 cases. The time from injury to operation was 2-6 days (mean, 3.4 days). There were 23 cases of trans-scaphoid perilunate dislocation, 10 cases of perilunate dislocation, and 2 cases of trans-triangular perilunate dislocation. Associated injuries included median nerve injury in 6 cases, radius styloid fracture in 8 cases, ulnar styloid fracture in 2 cases, and distal tibial fracture in 1 case. All the patients were treated by open reduction, Herbert screw fixation of scaphoid fractures, and Kirschner wire fixation in scapholunate joint, capitolunate joint, and lunotriquetral joint, and the intercarpal ligaments were repaired by Mitek bone anchor. Superficial wound infection occurred in 2 cases, and primary healing of incision obtained in others. Thirty-five patients were followed up 12-35 months (mean, 18 months). X-ray films showed fracture union in 21 cases of scaphoid fractures, and bone nonunion in 2 cases of scaphoid fractures. During the follow-up period, there was no avascular necrosis ofscaphoid or lunate. At last follow-up, the scapholunate angle, radiolunate angle, and wrist range of motion (ROM) in extension had no significant difference between affected and unaffected sides (P > 0.05). The wrist ROM in flexion and grip strength of affected side were not up to the levels of unaffected side (P < 0.05). According to the modified Mayo wrist scoring system, the score was 79.9 ± 10.7, which were excellent in 8 cases, good in 17 cases, fair in 7 cases, and poor in 3 cases, and the excellent and good rate was 71.4%. The disability of arm-shoulder-hand (DASH) questionnaires score was 21 ± 10. Traumatic osteoarthritis was observed in 2 cases.

Kirschner wire fixation in scapholunate joint, capitolunate joint, and lunotriquetral joint combined with bone anchor repair for the treatment of acute perilunate injury can get early stability of the carpal joint, favorable intercarpal ligament repair, and good recovery of wrist joint function.

To investigate the effect of flamingo exercise with or without KAT 2000 device on the balance problems due to senile OA. Ninety elderly osteoarthritic patients with balance impairment. Participants were randomly assigned into three groups; Kinesthetic ability trainer (KAT 2000) training group (Group 1) (n = 30), Flamingo training group (Group 2) (n = 30), Combined training group (Group 3) (n = 30) group. 45 minutes individualized training sessions as three times a week for 4 weeks were given to all participants. Patients were evaluated with Berg balance scale (BBS), kinesthetic ability trainer (KAT 2000) static and dynamic scores, timed up and go test (TUGT), walking speed (WS), Activities Specific Balance Confidence (ABC) Scale and Functional Reach Test (FRT) at the baseline and at the end of 4 weeks. At the end of the therapy, there were statistically significant improvements in KAT 2000 static and dynamic scores, TUGT scores, WS and ABC Scale in all groups (p < 0.05). At the end of the therapy there were statistically significant differences in Group 3 for KAT 2000 static and dynamic scores, TUGT scores, WS and ABC Scale than the other groups (p < 0.05). But there were no statistical difference in BBS and FRT score between the groups (p > 0.05).

Both flamingo and KAT2000 exercises device have positive effects on the balance problems due to senile OA. Combined with the KAT2000 device, the effects of flamingo exercises on balance disorder in senile osteoarthritis patients are more pronounced.

To test serum S100B protein levels in patients with and without neuropsychiatric systemic lupus erythematosus (NPSLE) and controls. 87 patients with SLE, 23 with and 64 without neuropsychiatric involvement, and 25 control subjects were prospectively evaluated. NPSLE diagnosis was made according to the American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Serum S100B protein levels were determined with a luminescence immunoassay. Statistical analysis was performed using Mann-Whitney and Kruskal-Wallis tests. Among the patients with NPSLE, 9 presented psychosis; 4, cranial neuropathy; 3, cerebrovascular disease; 1, seizures; 1, chorea; 1, peripheral polyneuropathy; 1, multiplex mononeuropathy; 3, dementia. Serum concentrations of S100B protein were significantly higher in patients with NPSLE (median 0.164 ng/ml, interquartile range 0.113-0.332) than in non-NPSLE patients (0.062 ng/ml, 0.026-0.109) and controls (0.088 ng/ml, 0.013-0.124) (p<0.001). Patients with anti-dsDNA antibodies had higher S100B protein levels (p = 0.001). No significant associations were found of lupus activity (among non-NPSLE cases), antiphospholipid antibodies, and reduced complement levels with S100B concentration.

Serum S100B protein level is raised in NPSLE, reflecting continuing neurological damage. The association of anti-dsDNA antibodies with higher S100B protein concentration deserves further study.

To investigate the characteristics of subcutaneous panniculitis-like T cell lymphoma (SPTCL) in order to facilitate prompt identification and proper treatment of this rare and heterogeneous disease entity. For 8 patients who had been misdiagnosed as rheumatic diseases but eventually confirmed as SPTCL though pathology and immunohistochemistry, a retrospective chart review was made with regard to their clinical symptoms, laboratory test results, pathological features, responses to therapy as well as outcomes. These 8 patients with a male to female ratio of 1:1 were initially misdiagnosed as a variety of rheumatic diseases such as erythema nodosa, nodular panniculitis, systemic vasculitis, etc. The period from the onset of symptoms to the confirmation of diagnosis as SPTCL was 28.6 months on average (range, 4 - 84 months). All the cases presented with multiple subcutaneous nodules, plaques or tumors which involved various anatomic sites including the head and neck, the trunk, and the extremities. Fever was the most frequently accompanying symptom (7/8), followed by lymphadenopathy (4/8), hepatomegaly (3/8), splenomegaly (3/8). Hemophagocytic phenomenon was seen in 3 cases. A total of 22 times of biopsy involving multiple anatomic sites were performed on these 8 cases with 2.75 times on average (range, 1 - 5 times). All cases demonstrated a dense lymphoid infiltrate with significant cellular heteromorphism located in the subcutaneous tissue. CD(3) was positive in the majority of the cases. Immunostaining for gammadeltaTCR was positive in one case. The anti-rheumatic therapy including steroids and immunosuppressants administered before the identification of SPTCL attained minimal therapeutic effect. In contrast, 6 cases gained partial response after chemotherapy except that the other 2 cases died of fatal pulmonary infiltration and subsequent infection.

SPTCL is a rare and heterogeneous entity which is unseldomly misdiagnosed as rheumatic disease. The anti-rheumatic therapy including steroids and immunosuppressants can attain minimal therapeutic effect. Early identification by means of histology and immunohistochemistry as well as immunostaining for PCR is critical for proper treatment.

Autoimmunity may play a role in endometriosis. The association between endometriosis and RA remains unknown. This study was conducted to identify any evidence for this relationship. This 13-year, nationwide, population-based, retrospective cohort study analysed the risk of RA in a cohort of individuals with endometriosis. We investigated the incidence of RA among patients with endometriosis using data from the Longitudinal Health Insurance Database 2000, which is maintained by the Taiwan National Health Research Institutes. We used propensity scores to match comorbidities in the two cohorts. Kaplan-Meier analysis and Cox proportional hazard model were employed to analyse the association between endometriosis and RA among patients with different potential risks. Patients with endometriosis [adjusted hazard ratio (HR) 1.75, 95% CI 1.27, 2.41], aged ≥45 years (adjusted HR 1.50, 95% CI 1.06-2.13) and with autoimmune disease (adjusted HR 6.99, 95% CI 2.84-17.21) had a significantly higher risk of RA. The analyses also showed that when stratified by age, comorbidities and medication use, the risk of RA in patients with endometriosis was also higher than in those without endometriosis.

This 14-year, nationwide, population-based retrospective cohort study revealed that patients with endometriosis have a higher risk of RA. In the clinical management of patients with RA, rheumatologists should be especially mindful of the possibility of underlying endometriosis.

Chronic pain can have detrimental effects on quality of life and a profound impact on one's identity. The Pictorial Representation of Illness- and Self-Measure (PRISM), is a visual tool designed to measure the self-illness separation (SIS) that represents the degree of schema-enmeshment (i.e., the degree to which the self-schema and the illness-schema come to overlap). Our aim was to investigate the relationship between schema-enmeshment and pain-related outcomes in patients with fibromyalgia. In this cross-sectional study, 114 patients with fibromyalgia completed self-report assessments of pain catastrophizing, pain severity and interference, impact of symptoms, anxiety, and depression. SIS was assessed using an iPad version of PRISM. Mediation analyses evaluated the mediating role of schema-enmeshment on the association between pain catastrophizing and fibromyalgia impact. A higher degree of schema-enmeshment was associated with greater pain catastrophizing, pain severity and interference, impact of symptoms, and depression. Moreover, a mediation analysis revealed that schema-enmeshment significantly mediated the association between pain catastrophizing and fibromyalgia impact (p < 0.001).

Our results indicate that schema-enmeshment is associated with greater intrusiveness of chronic pain on everyday life, thereby posing significant limitations on the emotional and physical well-being of fibromyalgia patients. Schema-enmeshment also appears to partly account for the deleterious effect of pain catastrophizing on disease impact. The PRISM is a simple tool that may uniquely capture the extent to which chronic pain and illness infiltrates and affects one's self-concept.

Osteoarthritis models were created by performing anterior cruciate ligament transections in 20 New Zealand rabbits. Rabbits were randomly divided into two groups of 10 and given intraarticular injections in their right knees weekly for 5 weeks, beginning in the third week post-operation. Injections given to the first group contained whole There was a statistically significant difference in the macroscopic grading results of the groups, with the

Intraarticular administration of

To evaluate an autoantibody profile in pediatric-onset systemic lupus erythematosus (SLE) patients to determine clinical and statistical associations with disease-associated manifestations. Sera from 53 SLE patients and 22 healthy individuals were collected. Antibodies to C1q, histone, chromatin, ribosomal P, dsDNA, and high-avidity dsDNA were measured by enzyme-linked immunosorbent assays. Patient records were evaluated for clinical and laboratory associations. The most prevalent autoantibodies found in the SLE cohort were anti-C1q antibodies (n = 32, 60%), which correlated significantly with proteinuria and decreased complement levels (P < 0.05). Anti-C1q and antihistone antibodies were significantly elevated in patients with class III/IV nephritis compared with class I/II/V nephritis (P = 0.041). SLE patients with active nephritis at the time of sample collection demonstrated significantly elevated levels of anti-C1q antibodies compared with those without active nephritis, also exhibiting 100% sensitivity for active nephritis, proteinuria, and urinary casts. Antibodies to C1q, dsDNA, histone, and chromatin were significantly elevated in patients with active disease (P < 0.01). Chart-documented anti-dsDNA antibodies were positive in 28 SLE patients, INOVA anti-dsDNA antibodies in 25 patients, and high-avidity anti-dsDNA antibodies in 8 patients. Antihistone correlated significantly with leukopenia and hemolytic anemia (P < 0.05).

This study indicates the importance of measuring anti-C1q antibodies in pediatric-onset SLE patients because elevated anti-C1q antibodies may be more indicative of renal disease activity, showing significant correlation with proteinuria, urinary casts, and active nephritis. Antibodies to C1q, histone, chromatin, and dsDNA exhibited the strongest association with clinical features, indicating the importance of measuring all of these antibodies in pediatric-onset SLE patients.

The presence of a new autoantibody system, anti-carbamylated protein (anti-CarP) antibodies, has been identified in rheumatoid arthritis (RA). The presence of anti-CarP antibodies was evaluated in samples taken from individuals who subsequently developed RA before and after onset of symptoms and related to previously analysed antibodies against citrullinated peptides (ACPA specificities) and anti-CCP2. A total of 252 individuals, with 423 samples from before onset of symptoms of RA, and 197 population controls were identified as donors to the Medical Biobank of Northern Sweden; 192 of them were also sampled at the time of diagnosis. All samples were analysed for anti-CarP IgG and anti-CCP2 antibodies using ELISAs. Ten different antibody reactivities against citrullinated antigens (ACPA specificities) were analysed using a custom-made microarray based on the ImmunoCAP ISAC system (Phadia). The concentration of anti-CarP antibodies was significantly increased in the pre-symptomatic individuals compared with controls (P<0.001) and also increased significantly after disease onset (P<0.001). The sensitivity for anti-CarP antibodies in the pre-symptomatic individuals was 13.9% (95% CI: 11 to 17.6) and 42.2% (95% CI: 35.4 to 49.3) following development of RA. Anti-CarP antibody positivity was found in 5.1% to 13.3% of individuals negative for anti-CCP2 or ACPA specificities. Presence of anti-CarP antibodies was significantly related to radiological destruction at baseline, at 24 months and also to radiological change (P<0.05, all).

The results indicate that anti-CarP antibodies are associated with disease development, even after adjusting for the presence of different ACPA fine specificities, and in anti-CCP2 negative individuals and contribute to the identification of a subset of patients with worse radiological progression of the disease independent of ACPA.