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ID PMID Title PublicationDate abstract
23597963 Relapsing polychondritis. 2013 May Relapsing polychondritis (RP) is a rare systemic autoimmune disease characterized by episodic, progressive inflammatory destruction of cartilage. It can occur as an overlap syndrome in patients with other rheumatologic conditions. The disease usually follows an indolent relapsing-remitting course, but occasionally it can progress rapidly and even cause death. Although auricular or nasal chondritis or peripheral arthritis without other significant organ involvement are usually treated with low-dose corticosteroids, other more severe disease manifestations may require treatment with high-dose corticosteroids or other immunosuppressive agents. Biological targeted therapies might prove to be effective treatments of this condition.
24878787 Frequency of antiparvovirus B19 antibodies in rheumatoid arthritis and systemic lupus eryt 2014 Jan OBJECTIVE: To determine the frequency of antiparvovírus B19 (B19) antibodies in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and the possible correlation of anti-B19 seropositivity with disease activity and quality of life. PATIENTS AND METHODS: Serum samples from 57 patients with RA, 45 with SLE and 65 healthy controls were used. We applied protocol with clinical data, and the Disease Activity Score 28 (DAS 28), Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Health Assessment Questionnaire (HAQ) indexes. The anti-B19 serology was done by enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean age of patients was 42.74 ± 14.09 years, and of controls was 38.38 ± 13.42 years. 79 patients had active disease (77.5%), and 23 had inactive disease (22.5%). Anti-B19 (IgG) was positive in 49 (86.0%; CI 95% 77.0-95.0) RA patients, 38 (84.4%; CI 95% 73.9-95.0) SLE patients, and 40 (61.5%; CI 95% 49.7-73.4) controls (p = 0.002). Anti-B19 (IgM) was positive in 3 (5.3%; CI 95% 0.0-11.1) RA patients, in 7 (15.6%; CI 95% 5.0-26,2) SLE patients, and in 1 (1.5%; CI 95% 0.0-4.5) control (p = 0.011).There was no correlation of anti-B19 reactivity with disease activity and with DAS 28, HAQ and SLEDAI indexes. CONCLUSION: This study demonstrated that the studied population is exposed to infection by B19, which demands attention with its manifestations, especially among patients at greatest risk, such as those immunosuppressed.
23782588 Pharmacokinetics and pharmacodynamics of tocilizumab after subcutaneous administration in 2013 Aug OBJECTIVES: To investigate the pharmacokinetics, pharmacodynamics, safety and efficacy of subcutaneous tocilizumab 162 mg weekly (QW) or every other week (Q2W) in rheumatoid arthritis patients on methotrexate. METHODS: This was a multicenter, open-label, randomized, parallel group study. Patients were randomly assigned to receive tocilizumab 162 mg subcutaneously QW or Q2W for 12 weeks. Pharmacokinetic and pharmacodynamic measurements were taken from baseline through to treatment end. Efficacy was assessed at baseline and Q4W thereafter. Safety and tolerability were monitored. RESULTS: 29 patients received tocilizumab treatment for 12 weeks. After final QW and Q2W dosing, mean ± SD for Cmax, Cmin and AUC0-168h/0-336h was 39.4 ± 18.1 and 10.7 ± 6.6 μg/ml, 27.9 ± 14.7 and 2.3 ± 3.2 μg/ml and 5,505 ± 2,632 and 2,332 ± 1,696 μg×h/ml. Median tmax was 2 - 3 days. Mean soluble interleukin-6 receptor (sIL-6R) complex concentration increased within 1 week and plateaued (670 ± 211 (QW); 387 ± 194 ng/ml (Q2W)) by final dosing; median C-reactive protein (CRP) levels decreased to below upper limit of normal after first and third doses; mean ± SD (range) reduction in Disease Activity Score using 28 joints at Week 12 was similar between groups (-2.5 ± 1.2 (-4 to -1); -3.1 ± 1.1 (-5 to -2)). Patients experiencing ≥ 1 adverse event were comparable between groups (71% vs. 80%). CONCLUSIONS: Greater tocilizumab exposure and sIL-6R elevation and more rapid CRP level normalization occurred with QW than with Q2W dosing. Both regimens demonstrated clinical benefit and were well tolerated.
22895833 Twenty-four-week clinical results of adalimumab therapy in Japanese patients with rheumato 2013 May OBJECTIVE: We evaluated patient drug adherence to and efficacy and safety of adalimumab (ADA) based on data collected from approximately 200 patients to retrospectively examine the best use of ADA in Japanese patients with longstanding rheumatoid arthritis (RA) managed in daily practice. METHODS: For explorative comparisons, patients were stratified by prior use or no use of biologics (Bio-naïve vs. Bio-switch) and concomitant use (+) or no use (-) of methotrexate (MTX) into four subgroups. The primary efficacy endpoint was extent of improvement in the Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) from baseline to 24 weeks assessed as European League Against Rheumatism (EULAR) good response. Secondary endpoints included ADA treatment continuation as represented by Kaplan-Meier survival curves and percentages of patients achieving remission as defined by DAS28-ESR <2.6. RESULTS: Overall, mean DAS28-ESR significantly decreased from 5.6 ± 1.2 at baseline to 4.1 ± 1.7 at week 24 (p < 0.0001), and >30 % of patients achieved EULAR good response. Subgroup analyses indicated that patients in the Bio-naïve and MTX (+) subgroup showed the highest EULAR good response rate of 37.3 % at week 24. The three most commonly reported adverse events (AEs) were skin allergies such as injection-site reactions, infections, and respiratory disorders such as interstitial lung lesions and organizing pneumonia. CONCLUSION: In conclusion, ADA therapy resulted in significant clinical response in established Japanese patients with RA treated in daily practice. It also demonstrated generally good safety and tolerability. It was suggested that the best use of ADA may be in biologically naïve patients with concomitant administration of MTX.
24495443 Prophylaxis for Pneumocystis pneumonia in patients with rheumatoid arthritis treated with 2014 Feb 5 INTRODUCTION: Pneumocystis pneumonia (PCP) is one of the most prevalent opportunistic infections in patients undergoing immunosuppressive therapy. In this article, we discuss risk factors for PCP development in patients with rheumatoid arthritis (RA) during the course of biologic therapy and describe a prophylactic treatment for PCP with trimethoprim/sulfamethoxazole (TMP/SMX). We also evaluate the effectiveness and safety of the treatment. METHODS: We retrospectively analyzed 702 RA patients who received biologic therapy and compared the characteristics of patients with vs. without PCP to identify the risk factors for PCP. Accordingly, we analyzed 214 patients who received the TMP/SMX biologic agents as prophylaxis against PCP at the start of treatment to evaluate their effectiveness and safety. RESULTS: We identified the following as risk factors for PCP: age at least 65 years (hazard ratio (HR) = 4.37, 95% confidence interval (CI) = 1.04 to 18.2), coexisting pulmonary disease (HR = 8.13, 95% CI = 1.63 to 40.0), and use of glucocorticoids (HR = 11.4, 95% CI = 1.38 to 90.9). We employed a protocol whereby patients with two or three risk factors for PCP would receive prophylactic treatment. In the study with 214 patients, there were no cases of PCP, and the incidence of PCP was reduced to 0.00 per 100 person-years compared with that before the procedure (0.93 per 100 person-years). There were no severe adverse events induced by the TMP/SMX treatment. CONCLUSIONS: RA patients with two or three risk factors for PCP who are receiving biologic therapy can benefit from safe primary prophylaxis.
24374632 Identification of key regulators for the migration and invasion of rheumatoid synoviocytes 2014 Jan 7 Rheumatoid synoviocytes, which consist of fibroblast-like synoviocytes (FLSs) and synovial macrophages (SMs), are crucial for the progression of rheumatoid arthritis (RA). Particularly, FLSs of RA patients (RA-FLSs) exhibit invasive characteristics reminiscent of cancer cells, destroying cartilage and bone. RA-FLSs and SMs originate differently from mesenchymal and myeloid cells, respectively, but share many pathologic functions. However, the molecular signatures and biological networks representing the distinct and shared features of the two cell types are unknown. We performed global transcriptome profiling of FLSs and SMs obtained from RA and osteoarthritis patients. By comparing the transcriptomes, we identified distinct molecular signatures and cellular processes defining invasiveness of RA-FLSs and proinflammatory properties of RA-SMs, respectively. Interestingly, under the interleukin-1β (IL-1β)-stimulated condition, the RA-FLSs newly acquired proinflammatory signature dominant in RA-SMs without losing invasive properties. We next reconstructed a network model that delineates the shared, RA-FLS-dominant (invasive), and RA-SM-dominant (inflammatory) processes. From the network model, we selected 13 genes, including periostin, osteoblast-specific factor (POSTN) and twist basic helix-loop-helix transcription factor 1 (TWIST1), as key regulator candidates responsible for FLS invasiveness. Of note, POSTN and TWIST1 expressions were elevated in independent RA-FLSs and further instigated by IL-1β. Functional assays demonstrated the requirement of POSTN and TWIST1 for migration and invasion of RA-FLSs stimulated with IL-1β. Together, our systems approach to rheumatoid synovitis provides a basis for identifying key regulators responsible for pathological features of RA-FLSs and -SMs, demonstrating how a certain type of cells acquires functional redundancy under chronic inflammatory conditions.
25231180 High levels of natural killer cells are associated with response to tocilizumab in patient 2015 Apr OBJECTIVES: We aimed to assess the effect of tocilizumab (TCZ), an IL-6 receptor inhibitor, on B, T, NK and NKT cells in patients with RA and to study the cell type predictors of remission. We also compared NK cells in patients with RA and in controls. METHODS: RA patients included in the study met the 2010 ACR/European League Against Rheumatism (EULAR) criteria, were receiving stable doses of steroids and had not received rituximab in the previous year. Different B and T cell subsets, NK cells and NKT cells were assessed by flow cytometry along with perforin A and granzyme B to estimate NK cell cytotoxicity. RESULTS: We included 92 RA patients, including 20 requiring TCZ treatment and 15 requiring anti-TNF drugs, and 25 controls. At baseline, the proportion of CD56(dim)CD16(+)CD3(-) NK cells was inversely correlated with the 28-joint DAS (DAS28). In TCZ-treated patients, the baseline proportion of CD3(-)CD56(+) NK cells was inversely correlated with the change in DAS28 at 3 months and the proportion was 3-fold greater for patients with DAS28 remission at 3 months than other patients. Change in the proportion of CD56(bri)CD16(-) NK cells was linearly correlated with change in the DAS28 at 3 months. The baseline proportion of NK cells did not predict change in disease activity at 3 months with anti-TNF therapy. The perforin content in NK cells increased with TCZ treatment. CONCLUSION: This study supports NK cell involvement in RA and in the TCZ mechanism of action. NK cells at baseline could be a predictive factor of TCZ response if results are confirmed.
24021273 Usefulness of US to show subclinical joint abnormalities in asymptomatic feet of RA patien 2013 Nov OBJECTIVES: The aim of the present study was to demonstrate the utility of ultrasound to show subclinical feet disease in RA. METHODS: The foot joints (talocrural, talocalcaneal, talonavicular, naviculocuneiform, calcaneocuboid, 5th tarsometatarsal and 1st to 5th metatarsophalangeal [MTP] joints) of 50 healthy subjects and 50 RA patients, with asymptomatic feet, were compared bilaterally. Statistical significance was set at 5%. RESULTS: Twenty-two joints were examined per individual (2200 in the entire sample). Significantly higher values were found in the RA group regarding quantitative synovitis in all joints recesses (p<0.003), the presence of synovitis (p<0.035) (except the 5thtarsometatarsal and 3rdMTP joint), power Doppler (PD) signals (p<0.029) (talocalcaneal, talonavicular, 1st, 2nd, 3rd and 4thMTP joints) and bone erosion (p<0.003) (except for the talocrural and talocalcaneal joints). Synovitis, PD signals and erosion were observed in 18.3% and 3.05% (p<0.001), 5.77% and 0.22% (p<0.001) and 34.45% and 2.85% (p<0.001) of the RA group and control group, respectively. Greater DAS-28, HAQ and FFI values were associated with ultrasound findings in only some joints (p<0.046). Interobserver agreement was ≤0.686 for semi-quantitative synovitis, ≤0.641 for quantitative synovitis, ≤0.474 for PD signals and ≤1.000 for erosion. Low Cohen Kappa values were found in the correlation between radiography and ultrasound (0.084-0.400). CONCLUSIONS. Ultrasound on RA asymptomatic feet demonstrated a significantly greater number of inflammatory changes in current activity (synovitis, PD signals) and sequelae (erosion) in comparison to control subjects. In the midfoot, the talonavicular joint has the greatest number of ultrasound findings.
25453625 A prospective, longitudinal study of patient satisfaction following total knee arthroplast 2015 Mar The purpose of this study was to evaluate the longitudinal variations in SF-36 physical and mental scores and the effects of demographics and comorbidities after TKA. This prospective study evaluated 108 men and 173 women who had a mean age of 66 years. All patients were followed for a minimum of five years and SF-36 physical and mental component scores were evaluated longitudinally. Physical scores steadily increased during the first year whereas mental component scores initially decreased in the first six weeks and then subsequently increased and both plateaued at one year. Demographic and social factors had a greater effect on physical component scores and comorbidities were more predictive of poor mental scores. Surgeons should counsel their patients that they will likely perceive the full benefit of TKA by one year, but in the first months may perceive worse outcomes.
23742283 Atypical ulcers. 2013 May Atypical ulcers of the skin challenge the dermatologist with respect to recognition, diagnosis, management, and treatment. The entire gamut of pathogenic categories including vascular, inflammatory, neoplastic, genetic, medication-related, and infectious processes may give rise to atypical ulcers. By definition, these ulcers are unusual, and accurate diagnosis may ultimately require the clinician to violate the dictum that "common things are common." Atypical ulcers may present with features that the clinician has not previously encountered, or may present with seemingly typical features that actually mislead due to phenotypic mimicry. Because skin ulcers are inherently tissue-destructive, and may reflect an underlying systemic disease process, there is heightened urgency to achieving an accurate diagnosis and initiating appropriate therapy.
24833787 Characterising the expression and function of CCL28 and its corresponding receptor, CCR10, 2015 Oct OBJECTIVE: This study was conducted to determine the expression pattern, regulation and function of CCL28 and CCR10 in rheumatoid arthritis (RA) pathogenesis. METHODS: Expression of CCL28 and CCR10 was assessed in RA compared with other arthritis synovial tissues (STs) or fluids (SFs) by histology or ELISA. The factors modulating CCL28 and CCR10 expression were identified in RA myeloid and endothelial cells by ELISA, FACS and Western blotting. The mechanism by which CCL28 ligation promotes RA angiogenesis was examined in control and CCR10-knockdown endothelial cell chemotaxis and capillary formation. RESULTS: CCL28 and/or CCR10 expression levels were accentuated in STs and SFs of patients with joint disease compared with normal controls and they were predominately coexpressed in RA myeloid and endothelial cells. We show that protein expression of CCL28 and CCR10 was modulated by tumour necrosis factor (TNF)-α and toll-like receptor 4 ligation in RA monocytes and endothelial cells and by interleukin (IL)-6 stimulation in RA macrophages. Neutralisation of CCL28 in RA SF or blockade of CCR10 on human endothelial progenitor cells (EPCs) significantly reduced SF-induced endothelial migration and capillary formation, demonstrating that ligation of joint CCL28 to endothelial CCR10+ cells is involved in RA angiogenesis. We discovered that angiogenesis driven by ligation of CCL28 to CCR10 is linked to the extracellular signal regulated kinase (ERK) cascade, as CCR10-knockdown cells exhibit dysfunctional CCL28-induced ERK signalling, chemotaxis and capillary formation. CONCLUSIONS: The overexpression of CCL28 and CCR10 in RA ST and their contribution to EPC migration into RA joints support the CCL28/CCR10 cascade as a potential therapeutic target for RA.
23281076 Curcumin in inflammatory diseases. 2013 Jan Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future.
25039414 Efficacy of patient-initiated follow-up clinics in secondary care: a systematic review. 2014 Dec Patient-initiated follow up (PIFU) is an initiative that allows patients to initiate hospital follow-up appointments on an 'as required' basis compared with the traditional 'physician-initiated' model. The main principle is to reduce inappropriate regular follow-up appointments. In this systematic review, we attempt to address its efficacy for outpatient secondary level care. Using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, an electronic literature search was performed independently by two authors using pre-defined search terms across EMBASE, Ovid MedLine, PubMed, PSYCINFO and the Cochrane Library databases. Articles were included if they specifically evaluated any aspect of PIFU. Studies evaluating non-outpatient-based, primary level-based and nurse-led clinic appointments were excluded. A total of 747 articles was reviewed, and six were finally included for the systematic review. Three studies analysed efficacy of PIFU with regards to rheumatological disease and found that there was no deleterious clinical effect and a trend towards increased satisfaction and quality of life including lower costs in the PIFU group. Two studies looked at PIFU and inflammatory bowel disease and identified some clinical benefit and lower costs and equivalent satisfaction and QoL with the PIFU group. A further study looked at PIFU in stage 1 breast cancer and did not find any significant differences in outcomes. There is evidence to suggest that PIFU systems result in fewer overall outpatient appointments in secondary care led services while maintaining equivalent if not better patient satisfaction, quality of life and clinical outcomes across a range of chronic conditions.
24011305 Gingival crevicular fluid and serum levels of APRIL, BAFF and TNF-alpha in rheumatoid arth 2013 Oct BACKGROUND: This study was performed to evaluate gingival crevicular fluid (GCF) and serum levels of a proliferation inducing ligand (APRIL) and B cell activating factor (BAFF) and compare this to differences between TNF-alpha levels in rheumatoid arthritis (RA), osteoporosis (OPR) and systemically healthy women with periodontal disease (SH). DESIGN: Gingival crevicular fluid (GCF) and serum samples were obtained before any periodontal intervention from 17 RA, 19 OPR patients and 13 SH women with periodontitis. Full-mouth clinical periodontal measurements were recorded. APRIL, BAFF and TNF-α levels were determined by ELISA. Statistical analysis was performed using multivariate analysis, ANOVA and Spearman correlation. RESULTS: Pocket depths differed in site-specific comparisons, but otherwise clinical measurements were similar in the three study groups. Multivariate least squares regression ANOVA adjusted for age and for plaque index indicated that total amounts of TNF-α and concentrations of TNF-α, BAFF and APRIL were significantly greater in the RA patients than in the SH group (p<0.05), and GCF concentrations of BAFF were greater in OPR patients than in SH. Serum TNF-α and BAFF were significantly higher in the RA group compared to SH (p<0.05) and serum TNF-α was greater in RA than in OPR (p<0.05). APRIL and BAFF correlated with RANKL levels in GCF and serum (p<0.05). CONCLUSION: Despite long-term usage of anti-inflammatory drugs in the RA and OPR patients, increased TNF-family cytokines, might suggest that these patients have a propensity to overproduce these inflammatory mediators but whether this results from greater disease activity or contribute to greater disease activity remains moot.
23238923 Mid-term survival following primary hinged total knee replacement is good irrespective of 2014 Mar PURPOSE: The use of 'hinged' knee prostheses for primary knee arthroplasty procedures is increasing. This analysis reports the rates of implant survival, modes of failure, revision details and functional outcomes with particular reference to the primary indication for surgery for a cohort of patients treated with primary hinged knee replacement. METHODS: Systematic review with supplementary analysis using data from the National Joint Registry and Department of Health. Analysis included 964 patients undergoing primary hinged knee replacement between April 2003 and December 2010. Survival at a maximum of 7 years was calculated for the group as a whole and dependent upon the indication for surgery (osteoarthritis vs. rheumatoid/inflammatory arthritis vs. post-traumatic arthritis). Functional outcomes (pre- and post-operative Oxford Knee and Euroqol-5D scores and post-operative satisfaction) were available for 46 patients. RESULTS: In total, 20 cases required revision. The 5-year survival rate (96.8% [95% CI 95.1-98.4%]) was not dependent upon the primary surgical indication (p = n.s.). The commonest reasons for revision were infection (8 cases), peri-prosthetic fracture (4 cases) and aseptic loosening (3 cases). Patients reported substantial improvements in their Oxford Knee Score (mean improvement = 17.6, [95% CI 14.4-20.8]) and EQ5D index (mean improvement = 0.357, [95% CI 0.248-0.467]). Levels of post-operative satisfaction were high. CONCLUSIONS: Hinged knee replacement can be considered as a viable alternative to more traditional unconstrained designs in the complex primary setting. These findings are clinically relevant as they support the increasing use of hinged knee replacements for the arthritic knee in which there is concomitant severe bone loss, deformity or instability. Surgeons using these implants can have confidence that their mid-term performance is comparable to more conventional knee designs. LEVEL OF EVIDENCE: Prospective cohort study, Level II.
25252608 Individual patient monitoring in daily clinical practice: a critical evaluation of minimal 2015 Mar PURPOSE: In daily practice, physicians translate knowledge from clinical trials to practice, to improve health in individual patients. To help interpret meaningful change on disease outcome measures, the concept of minimal important change (MIC) was conceived. The objective of this study was to investigate whether MIC values are suited for individual patient monitoring. METHODS: Three main elements of the MIC concept were evaluated: (1) MIC values for improvement and deterioration were determined, and the amount of misclassification present in quantifying minimal change was analyzed. (2) Discordance between change categories (improved, unchanged, deteriorated), defined by the MIC values, and patients' satisfaction with their health was inspected. (3) Discordance between change categories, defined by MIC values, and patients' willingness to alter therapy was inspected. RESULTS: MIC value analysis was based on 469 patients with RA seen in daily practice. The chance of falsely classifying health change of an individual patient was high (false-positive range 19-30 % and false-negative range 43-72 %). Of patients classified as improved, 24 % were not satisfied with their health and 69 % were not willing to change therapy. Of patients classified as deteriorated, 54 % were satisfied with their health and 57 % were not willing to change therapy. CONCLUSIONS: The misclassification in the quantification of change and high proportions of discordance between change categories defined by MIC cutoff values and patients' satisfaction and willingness to alter therapy indicate that MIC values as such are not suited for individual patient monitoring.
25179893 Total knee arthroplasty with rotating-hinge Endo-Model prosthesis: clinical results in com 2014 Nov INTRODUCTION: Rotating-hinge knee implants are highly constrained devices able to provide the stability needed for arthroplasty in case of severe bone loss and complex instability. Notable doubts still exist in using rotating-hinge devices, mainly due to risk of mechanical failure and risk of infection. MATERIALS AND METHODS: We retrospectively evaluated the functional and clinical outcomes in a series of patients treated with the rotating-hinge Endo-Model prosthesis either for primary or revision total knee arthroplasty. Between 1997 and 2009 we implanted 123 Endo-Model prosthesis (118 patients) at our institution. At the time of this study we could evaluate 45 prosthesis (25 primary and 20 revision TKAs) from the clinical and radiological site, with average follow-up of 42.2 months. RESULTS: During the follow-up period, three patients reported complications, which in two cases finally led to revision with explantation. Mean survival of the implants attested at 93.3 %. The average post-operative clinical Knee Society score in the evaluated series was 94.2, the functional one 78.7. The average range of motion was 0°-108°. No signs of joint instability or misalignment were noted. Pain was present in a minority of patients, but always at a mild/occasional extent. No evidences of loosening or implant failure have been reported. No substantial divergences in the outcomes have been found across different patient categories after stratification in agreement with the Knee Society. CONCLUSIONS: Coherent with previously published works, we confirm the Endo-Model prosthesis to provide excellent pain relief, restoration of walking capacity and intrinsic knee stability both in complex primary and in revision knee arthroplasty, with good or excellent results in the majority of patients and acceptable complication rate.
25078097 Distinct effects of soluble and membrane-bound fas ligand on fibroblast-like synoviocytes 2014 Dec OBJECTIVE: Injection of agonistic anti-Fas antibody has been shown to decrease disease symptoms in mouse models of arthritis. Additionally, membrane-bound FasL (mFasL) has been shown to induce cell death in fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) patients. However, levels of soluble FasL (sFasL) are increased in the joints of RA patients and have been associated with disease severity, indicating that mFasL and sFasL play opposing roles in RA. The purpose of this study was to analyze the effects of FasL on RA FLS responses. METHODS: The responses of FLS from RA and osteoarthritis (OA) patients to soluble and oligomeric FasL, the latter mimicking mFasL, were analyzed by fluorescence-activated cell sorting and proliferation assays, using 3 different FasL variants. The signaling pathways that trigger FasL responses were characterized by Western blotting. RESULTS: We found that mFasL and sFasL have distinct roles in RA FLS. Crosslinked FasL preferentially induced apoptosis, whereas sFasL stimulated proliferation. Moreover, sFasL activated several signaling pathways in RA FLS, such as ERK-1/2, phosphatidylinositol 3-kinase, caspase 8, and JNK, with a prominent role of JNK, since only the blockade of this pathway rendered FLS more susceptible to FasL-induced apoptosis. Crosslinked FasL induced apoptosis in FLS from OA patients, but sFasL failed to stimulate their proliferation. CONCLUSION: Our findings suggest that sFasL is a disease promoter in RA, a finding consistent with previous reports describing a tumor-promoting role of FasL. Therefore, blocking of sFasL could be a therapeutic strategy for RA.
23537796 False decrease of HBsAg S/CO values in serum with high-concentration rheumatoid factors. 2013 Jun OBJECTIVES: To investigate whether high-concentration RFs cause false decrease of S/CO values of serum HBsAg. DESIGN AND METHODS: Serum HBsAg was determined in 100 RF-positive sera using one-step ELISA. Twenty-three HBsAg-negative sera with high-concentration RFs were selected randomly to perform dilution with mixed normal sera. Serum models consisting of HBsAg and high-concentration RFs were made by blending high-concentration RFs and HBsAg-positive sera at the ratio of 9:1. RESULTS: In the 23 samples, one-step ELISA showed that HBsAg-positive rate was 69.57% at dilution of 1:2, 60.87% at dilution of 1:4 and 40.00% at dilution of 1:8, whereas two-step ELISA showed that it was 100% without any dilution. Thirty serum models were made and divided into six groups. Median S/CO value of HBsAg was 3.00 in control, whereas it ranged from 0.13 to 1.78 in the six groups. CONCLUSIONS: High-concentration RFs cause false decrease of S/CO values of HBsAg using one-step ELISA.
24657949 Intracellular delivery of desulfated heparin with bile acid conjugation alleviates T cell- 2014 Jun 10 Heparin has a potential regulatory role in inflammatory diseases. However, the anticoagulant activity and poor oral bioavailability of heparin limit its use as an anti-inflammatory agent. Conjugation of bis-deoxycholic acid to 6-O-desulfated low molecular weight heparin (6DSHbD) was efficiently internalized by activated endothelial cells via a 2-step model, in which heparin attaches to adhesion molecules that facilitate accessibility of the bile acid conjugate to membrane transporters. The critical role of P-selectin during endothelial cell uptake of 6DSHbD by arthritic tissue was confirmed in p-selectin(-/-) arthritic mice. Intracellular 6DSHbD inhibited transcellular diapedesis of T cells through activated endothelial cells and impaired both the formation of ICAM-1-rich docking structures at the T cell contact surface and subsequent cytoskeletal rearrangement. Furthermore, 6DSHbD blocked activation of RhoA-GTPase and phosphorylation of ezrin/radixin/moesin induced by ICAM-1 cross-linking on activated endothelial cells, thereby impairing lymphocyte transcellular transmigration. After oral administration 6DSHbD was preferentially delivered to inflamed joint tissue, particularly in and around post-capillary venular endothelium and inhibited effector T cell homing to arthritic joints. Aggravation of collagen-induced arthritis conferred by the transfer of effector T cells was suppressed by oral 6DSHbD. Thus, intracellular heparin exerts anti-inflammatory effects through the inhibition of RhoA-dependent transendothelial recruitment of T cells and may have applications in the treatment of chronic inflammatory arthritis.