Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
22589376 Chemokine receptor CCR1 antagonist CCX354-C treatment for rheumatoid arthritis: CARAT-2, a 2013 Mar OBJECTIVES: CCX354-C is a specific, orally administered antagonist of the C-C chemokine receptor 1, which regulates migration of monocytes and macrophages to synovial tissue. This clinical trial evaluated the safety and efficacy of CCX354-C in patients with rheumatoid arthritis (RA). METHODS: CARAT-2 is a 12-week double-blind, randomised, placebo controlled trial in 160 patients with RA, with 68 tender joint count and 66 swollen joint count ≥8 and C-reactive protein (CRP) >5 mg/l, despite being on methotrexate for at least 16 weeks. Subjects received placebo, CCX354-C 100 mg twice daily, or 200 mg once daily for 12 weeks. Endpoints included safety (primary) and RA disease activity assessments based on American College of Rheumatology (ACR) response, and changes in 28-joint disease activity score-CRP, individual ACR components, as well as soluble bone turnover markers. RESULTS: CCX354-C was generally well tolerated by study subjects. The ACR20 response at week 12 was 39% in the placebo group, 43% in the 100 mg twice daily group (difference and 95% CI compared with placebo, 4.5 (-14.1 to 23.1); p=0.62) and 52% in the 200 mg once daily group (13.0 (-5.8 to 31.8); p=0.17) in the intention-to-treat population, and 30% in the placebo group, 44% in the 100 mg twice daily group (14.4 (-5.9 to 34.8); p=0.17), and 56% in the 200 mg once daily group (25.8 (5.3 to 46.4); p=0.01) in the prespecified population of patients satisfying CRP and joint count eligibility criteria at the screening and day 1 (predose) visits. CONCLUSIONS: CCX354-C exhibited a good safety and tolerability profile and evidence of clinical activity in RA.
24754273 Phase III, multicenter, open-label, long-term study of the safety of abatacept in Japanese 2014 Sep OBJECTIVES: To examine the long-term safety of intravenous (IV) abatacept treatment in Japanese patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) or other conventional or biologic disease-modifying antirheumatic drugs. METHODS: This Phase III, open-label, long-term study (NCT00484289) comprised Japanese patients with RA who had completed abatacept Phase I or Phase II studies, and new patients intolerant to MTX. Patients from Phase I and Phase II studies received a weight-tiered dosing equivalent of 10 mg/kg abatacept, with MTX at doses up to 8 mg/week; newly enrolled patients received weight-tiered 10 mg/kg abatacept monotherapy. Safety and efficacy were assessed. RESULTS: A total of 217 patients (Phase I, n = 13; Phase II, n = 178; newly enrolled, n = 26) were treated with IV abatacept for a mean of 3 years. Serious adverse events occurred in 67/217 (30.9%) patients. Most adverse events were mild or moderate. For all cohorts combined, American College of Rheumatology 20% response rates ranged from 61.3 to 81.8% for as-observed and last observation carried forward analyses over 192 weeks. Following initial response, clinical and functional outcomes were maintained for up to 3 years. CONCLUSIONS: In Japanese patients with RA, IV abatacept with and without background MTX showed tolerable safety and sustained efficacy over 3 years.
24590021 A roadmap to promote clinical and translational research in rheumatoid arthritis-associate 2014 Mar 1 Rheumatoid arthritis (RA) is a systemic inflammatory disorder affecting approximately 1.3 million adults in the United States. Approximately 10% of these individuals with RA have clinically evident interstitial lung disease (RA-ILD), and an additional one-third demonstrate subclinical ILD on chest CT scan. The risk of death for individuals with RA-ILD is three times higher than for patients with RA without ILD, with a median survival after ILD diagnosis of only 2.6 years. Despite the high prevalence and mortality of RA-ILD, little is known about its molecular features and its natural history. At present, we lack a standard validated approach to the definition, diagnosis, risk stratification, and management of RA-ILD. In this perspective, we discuss the importance of clinical and translational research and how ongoing research efforts can address important gaps in our knowledge over the next few years. Furthermore, recommendations are made to design multicenter collaborative studies that will expedite the development of clinical trials designed to decrease the significant morbidity and mortality associated with RA-ILD.
24297381 Sarilumab, a fully human monoclonal antibody against IL-6Rα in patients with rheumatoid a 2014 Sep OBJECTIVES: To evaluate safety and efficacy of weekly (qw) and every other week (q2w) dosing of sarilumab, a fully human anti-interleukin 6 receptor α (anti-IL-6Rα) monoclonal antibody, for moderate-to-severe rheumatoid arthritis (RA). METHODS: In this dose-ranging study, patients (n=306) with active RA, despite methotrexate, were randomly assigned to placebo or one of five subcutaneous doses/regimens of sarilumab: 100 mg q2w, 150 mg q2w, 100 mg qw, 200 mg q2w, 150 mg qw for 12 weeks, plus methotrexate. The primary end point was ACR20 at Week 12. Secondary endpoints included ACR50, ACR70, Disease Activity Score in 28 joints (C reactive protein). Safety, pharmacokinetics, pharmacodynamics and efficacy in population subgroups were assessed. RESULTS: The proportion of patients achieving an ACR20 response compared with placebo was significantly higher for sarilumab 150 mg qw (72.0% vs 46.2%, multiplicity adjusted p=0.0203). Higher ACR20 responses were also attained with 150 mg q2w (67%; unadjusted (nominal) p=0.0363) and 200 mg q2w (65%; unadjusted p=0.0426) versus placebo. Sarilumab ≥150 mg q2w reduced C reactive protein, which did not return to baseline between dosing intervals. Infections were the most common adverse event; none were serious. Changes in laboratory values (neutropenia, transaminases and lipids) were consistent with reports with other IL-6Rα inhibitors. CONCLUSIONS: Sarilumab improved signs and symptoms of RA over 12 weeks in patients with moderate-to-severe RA with a safety profile similar to reports with other IL-6 inhibitors. Sarilumab 150 mg and sarilumab 200 mg q2w had the most favourable efficacy, safety and dosing convenience and are being further evaluated in Phase III.
25267562 Patient expectations and long-term outcomes in rheumatoid arthritis patients: results from 2015 Apr Little evidence exists to understand the influence of patient expectations on outcomes for silicone metacarpophalangeal arthroplasty (SMPA). The purpose of this paper is to compare long-term treatment outcome experiences regarding hand function/appearance for a surgical and nonsurgical cohort of rheumatoid arthritis (RA) patients and contrast them to expectations at baseline. This sample is part of a larger multicenter prospective cohort study of RA patients enrolled from 2004 to 2008. A total of 169 RA patients with severe deformities at the metacarpophalangeal (MCP) joints were recruited in the original study. Expectations for SMPA were collected at enrollment. A follow-up patient-reported questionnaire was completed at long-term follow-up. Baseline expectation questionnaires were collected from 137 patients, and follow-up data from 84 patients (average 6.7 years follow-up). At baseline, a significantly higher percent of patients who chose surgery expected to do "Anything I want" or "More activities than I do now" 1 year from enrollment than those who chose nonsurgical treatment. At follow-up, surgical patients remained more likely to indicate that they were currently able to do "Anything" or "More activities" than nonsurgical patients. A higher percentage of surgical patients were "very satisfied" or "quite satisfied" with their treatment compared to nonsurgical patients. RA subjects who chose SMPA reported greater expectations for surgery prior to surgery and also greater levels of hand function and satisfaction at long-term follow-up.
23547212 Early local swelling and tenderness are associated with large-joint damage after 8 years o 2013 May OBJECTIVE: To assess whether early swelling and tenderness in large joints in patients with rheumatoid arthritis (RA) is predictive of later local damage and whether this leads to functional disability. METHODS: Two-year clinical and 8-year radiological followup data from the BeSt study (trial numbers NTR262 and NTR265), a randomized controlled treat-to-target trial, were used. The association between early local joint swelling and/or tenderness (at least once, or for ≥ 2 consecutive visits) and later large-joint damage (Larsen score ≥ 1) was assessed using generalized estimating equations. The association between large-joint damage and functional ability [by Health Assessment Questionnaire (HAQ)] was assessed using logistic and linear regression analysis. RESULTS: Clinical and 8-year radiological data were available for 290 patients. Concomitant local joint swelling and tenderness at least once in the first 2 years was independently associated with damage of the large joints (OR 2.5, 95% CI 1.7-3.6), as was swelling without tenderness (OR 2.0, 95% CI 1.1-3.6). Stronger effects were seen for persistent swelling and/or tenderness. Other independent predictors for joint damage were baseline erythrocyte sedimentation rate (OR 1.01, 95% CI 1.01-1.02) and the presence of rheumatoid factor and/or anticitrullinated protein antibodies (OR 2.5, 95% CI 1.5-4.1; and OR 2.2, 95% CI 1.3-3.8, respectively). Patients with large-joint damage had a higher HAQ score after 8 years than patients without (difference 0.15). CONCLUSION: Early local swelling and tenderness are independent predictors of later joint damage in these joints after 8 years of Disease Activity Score-guided treatment in patients with RA. This suggests that suppression of local inflammation could help prevent local damage and functional disability.
23762095 Targeting BCL2 family in human myeloid dendritic cells: a challenge to cure diseases with 2013 Rheumatoid arthritis (RA) and Langerhans cell histiocytosis (LCH) are common and rare diseases, respectively. They associate myeloid cell recruitment and survival in inflammatory conditions with tissue destruction and bone resorption. Manipulating dendritic cell (DC), and, especially, regulating their half-life and fusion, is a challenge. Indeed, these myeloid cells display pathogenic roles in both diseases and may be an important source of precursors for differentiation of osteoclasts, the bone-resorbing multinucleated giant cells. We have recently documented that the proinflammatory cytokine IL-17A regulates long-term survival of DC by inducing BCL2A1 expression, in addition to the constitutive MCL1 expression. We summarize bibliography of the BCL2 family members and their therapeutic targeting, with a special emphasis on MCL1 and BCL2A1, discussing their potential impact on RA and LCH. Our recent knowledge in the survival pathway, which is activated to perform DC fusion in the presence of IL-17A, suggests that targeting MCL1 and BCL2A1 in infiltrating DC may affect the clinical outcomes in RA and LCH. The development of new therapies, interfering with MCL1 and BCL2A1 expression, to target long-term surviving inflammatory DC should be translated into preclinical studies with the aim to increase the well-being of patients with RA and LCH.
23106574 An investigation of rheumatoid arthritis loci in patients with early-onset psoriasis valid 2013 Apr BACKGROUND: Phenotypically diverse autoimmune conditions share common genetic susceptibility loci and underlying molecular pathways. OBJECTIVES: By systematically searching for single nucleotide polymorphisms (SNPs) associated with another autoimmune disease, rheumatoid arthritis (RA), we aimed to elucidate novel genetic markers of psoriasis. METHODS: We investigated 18 SNPs, previously confirmed as being associated with RA, in a U.K. cohort of 623 patients with early-onset psoriasis (presenting before age 40 years), comparing them with 2662 control subjects. RESULTS: Our findings confirm the association of early-onset psoriasis with REL (rs13031237, P=0·0027). The minor allele of REL had opposing effects upon susceptibility to disease in patients with psoriasis and RA. CONCLUSION: Similar exploration of additional autoimmune loci and fine mapping of such regions may provide further insight into the genetics and molecular pathophysiology of psoriasis.
24280444 Minimum effective dosages of anti-TNF in rheumatoid arthritis: a cross-sectional study. 2014 Mar AIMS: To evaluate the modified dosages of anti-TNF in controlling disease activity in rheumatoid arthritis (RA) measured by DAS28-ESR. PATIENTS AND METHODS: Cross-sectional study: RA patients treated with etanercept (ETN), adalimumab (ADA) or infliximab (IFX), at standard or modified doses. MAIN VARIABLES: dosage, concomitant disease modifying drugs (DMARDs), DAS28-ESR. RESULTS: 195 RA patients included (79% women, mean age 58.1 years): ETN=81, ADA=56, IFX=58. Mean disease duration and time to first biological treatment was higher in IFX group (P=.01). Patients distribution by dosage: standard: ETN (72.8%), ADA (69.6%), IFX (27.6%); escalated: IFX (69%), ADA (5.4%), ETN (0%); reduced: ETN (27.1%), ADA (25%), IFX (3.4%). Concomitant DMARDs use was lower in ETN (58.2%) than ADA (66.07%) and IFX (79.31%). Higher proportion of responders (DAS28 ≤3.2) in ADA (65.3%) and ETN (61.7%) than IFX (48.3%). CONCLUSIONS: RA clinical control can be preserved with modified anti-TNF dosages. Controlled prospective studies should be performed to define when therapy can be tailored and for which patients.
24056519 IL-22/IL-22R1 axis and S100A8/A9 alarmins in human osteoarthritic and rheumatoid arthritis 2013 Dec OBJECTIVES: Fibroblast-like synoviocytes (FLSs) are crucial players in the pathogenesis of synovitis in rheumatic diseases. Targeting FLS activation represents an approach to the development of therapeutic strategies. Our aim was to investigate whether the microenvironment of inflamed joints could modulate the expression of IL-22 and IL-22R1 on OA and RA FLSs. We also examined the effect of IL-22 on FLS activation as well as on their IL-17-related responses. METHODS: IL-22 and IL-22R1 expression was studied by RT-PCR and immunoblotting. Proliferation was measured by an ELISA kit. IL-17 receptors, p19IL-23 and alarmins were analysed by RT-PCR. IL-17 receptor expression was evaluated by flow cytometry. MMP1 and IL-23 were measured by ELISA. S100A8/A9 expression was detected by immunofluorescence and ELISA. Signal transducer and activator of transcription 3 (STAT3) phosphorylation was quantified using a cell-based ELISA kit. RESULTS: IL-22 and IL-22R1 were expressed constitutively in FLSs. We demonstrated that S100A8 and S100A9 were synthesized in FLSs. We reported that inflammatory mediators increased the expression of the IL-22/IL-22R1 axis, amplifying FLS activation. IL-22 enhanced FLS proliferation and up-regulated MMP1 and S100A8/A9 production. STAT3 phosphorylation was induced after IL-22 treatment and the stimulatory effect of IL-22 on S100A8/A9 was reduced after the activities of Janus kinase 2 (JAK2) and JAK3 were blocked. We showed an inhibitory action of IL-22 on IL-23 and IL-17RC expression in RA FLSs and on IL-17RA in OA FLSs. CONCLUSION: Therapies based on the pharmacological disruption signalling of IL-22 could be beneficial for the treatment of rheumatic diseases. The restricted expression of IL-22R1 to non-lymphoid cells could lead to a reduction of side effects mediated by immune responses.
24286137 Role of neutrophils in systemic autoimmune diseases. 2013 Oct 2 Neutrophils have emerged as important regulators of innate and adaptive immune responses. Recent evidence indicates that neutrophils display marked abnormalities in phenotype and function in various systemic autoimmune diseases, and may play a central role in initiation and perpetuation of aberrant immune responses and organ damage in these conditions. This review discusses the putative roles that neutrophils and aberrant neutrophil cell death play in the pathogenesis of various systemic autoimmune diseases, including systemic lupus erythematosus, small vessel vasculitis and rheumatoid arthritis.
23839609 Failure of anti-TNF therapy to reactivate previously septic prosthetic joints. 2013 Jul 8 A patient with long-standing rheumatoid arthritis was admitted with Streptococcus pneumoniae septicaemia and bilateral septic knee joints. He was treated conservatively with intravenous antibiotics and arthroscopic washouts and discharged home on oral antibiotics. Six months posthospital discharge, following re-exacerbation of arthritis, an informed consent was given by the patient to continue antitumour necrosis factor therapy. After 5 years of observation, there has been no recurrence of sepsis and the rheumatoid arthritis remains in remission.
24263146 Prevalence and correlates of metabolic syndrome in patients with rheumatoid arthritis in A 2013 Dec BACKGROUND: The increased mortality reported among patient with rheumatoid arthritis (RA) has been attributed to cardiovascular disease. Metabolic syndrome (MS) is a cluster of major risk factors for cardiovascular disease such as dyslipidemia, obesity, hypertension, and diabetes. There is a lack of reporting on the prevalence of MS in RA patients in Argentina. OBJECTIVES: The objectives of this study were to determine and compare the frequency of MS in patients with RA and a control group and to assess the factors associated with MS. METHODS: This is a cross-sectional study involving 1033 (409 RA and 624 age- and sex-matched control subjects) patients, followed up at 9 different rheumatology units in Argentina. Metabolic syndrome was defined according to the Adult Treatment Panel III (ATP III) and the International Diabetes Federation (IDF). The relationship between demographic variables, clinical data (disease duration, disease activity by Disease Activity Score of 28 joints, presence of rheumatoid factor [RF] and/or anti-cyclic citrullinated peptide antibody, presence of extra-articular manifestations), pharmacological treatment, and MS was examined by descriptive statistics. Variables with P ≤ 0.10 in these analyses were then examined by logistic regression. RESULTS: The frequency of MS in RA patients and the control group was 30% versus 39% (P = 0.002) when defined as per the ATP III and 35% versus 40% (P = 0.10) as per the IDF. Variables independently associated with MS in RA patients were age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.06 [P = 0.01] for the ATP III and OR, 1.03; 95% CI, 1.01-1.05 [P < 0.001] for the IDF), the presence of RF and/or anti-cyclic citrullinated peptide antibody (OR, 2.91; 95% CI, 1.11-7.61 [P = 0.02] for the ATP III and OR, 2.37; 95% CI, 1.09-5.16 [P = 0.02] for the IDF), and the use of hydroxychloroquine (OR, 0.48; 95% CI, 0.23-0.97 [P = 0.04] only for the IDF). CONCLUSIONS: In this study, we were not able to demonstrate a higher frequency of MS in RA patients. However, older patients with positive RF or CCP have a higher risk of MS. A protective effect to develop MS was seen in the population treated with hydroxychloroquine.
23001900 The TTTT B lymphocyte stimulator promoter haplotype is associated with good response to ri 2013 Jan OBJECTIVE: To investigate the polymorphisms in the promoter region of the B lymphocyte stimulator (BLyS) gene as markers of response to rituximab (RTX) in rheumatoid arthritis (RA). METHODS: The study was first conducted in 152 Italian RA patients and then replicated in an additional 117 RA patients (73 Italian, 44 British). The European League Against Rheumatism response criteria were used to evaluate the response rate at months 4 and 6 after the first cycle of RTX, by means of the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate; patients were classified according to the best response shown between months 4 and 6. BLyS promoter polymorphisms were analyzed by polymerase chain reaction followed by the analysis of the restriction fragments, BLyS promoter haplotypes were analyzed using the expectation-maximization algorithm, and BLyS serum levels were analyzed using enzyme-linked immunosorbent assay. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs). RESULTS: The TTTT BLyS promoter haplotype appeared to be significantly associated with response to RTX only in the subset of seropositive patients (those positive for rheumatoid factor and/or anti-cyclic citrullinated peptide). The replication study confirmed that this association was limited to seropositive RA patients in whom treatment with anti-tumor necrosis factor (anti-TNF) agents had previously failed. In the whole series of seropositive patients in whom anti-TNF agents had previously failed, patients carrying the TTTT BLyS promoter haplotype were more prevalent in good responders (18 of 43 [41.9%]) than in moderate responders (20 of 83 [24.1%]) or in nonresponders (1 of 21 [4.8%]) (for good responders versus nonresponders, OR 14.4 [95% CI 1.77-117.39], P=0.0028). Furthermore, multivariate analysis selected the TTTT BLyS promoter haplotype as an independent marker of good response to RTX (for good responders versus nonresponders, OR 16.2 [95% CI 1.7-152.5], P=0.01; for good responders versus moderate responders and nonresponders combined, OR 3.1 [95% CI 1.2-7.8], P=0.02). The relationship between BLyS polymorphisms and BLyS serum levels remained unclear. CONCLUSION: BLyS promoter genotyping may be suitable for identifying seropositive RA patients who may have a good response to RTX after anti-TNF agents have failed.
24526219 Amelioration of small bowel injury by switching from nonselective nonsteroidal anti-inflam 2014 BACKGROUND/AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in patients with rheumatoid arthritis (RA) but have several side effects including mucosal damage in the small intestine. We aimed to evaluate whether the small bowel injury is ameliorated by switching from nonselective NSAIDs to celecoxib in patients with RA. METHODS: Sixteen patients with RA who were treated with nonselective NSAIDs were enrolled in this study. Nonselective NSAIDs were converted to celecoxib for 12 weeks. Capsule endoscopy was performed before and after treatment with celecoxib. Videos were screened by gastroenterologists blinded to the patients' treatment. RESULTS: Before the administration of celecoxib, reddened folds, denuded areas, petechiae/red spots and mucosal breaks were observed in 63, 63, 88 and 69% of the patients, respectively. In the 14 patients who completed this study, conversion to celecoxib significantly reduced the number of petechiae/red spots, the number of mucosal breaks, and Lewis scores. RA activity and cytokine levels in the peripheral blood were not significantly different before and after treatment with celecoxib. CONCLUSIONS: The incidence of small bowel injury by nonselective NSAIDs is high in patients with RA. Conversion from nonselective NSAIDs to celecoxib can be useful for protecting patients with RA from small bowel injury.
22780867 Application of decoy oligonucleotides as novel therapeutic strategy: a contemporary overvi 2013 Mar Molecular therapy is emerging as a potential strategy for the treatment of many diseases. Correct regulation of gene expression is essential for both, to normal development and proper functioning of the all the organisms. Even after four decades of intensive research, it is still a major problem from regulatory and technical point of view, to replace defective genes. The technology of decoy oligonucleotides has received considerable attention to treat and cure a variety of diseases and abnormal physiological conditions, because they provide a rational way to design and selective regulation of a specific gene expression. Decoy oligonucleotides are widely used as inhibitors of specific gene expression because they can offer exciting possibility of expression and blocking of a particular gene without any changes in the functions of other genes. Advances in the decoy oligonucleotides are rapidly paving the way to new insights into the origin and treatment of inflammatory, cancer and/or other immune disorders. The review covers the progress achieved towards the development of decoy oligonucleotides as a potential strategy in a new class of molecular therapy.
24641737 Proximal ulnar stump stability after using the pronator quadratus muscle transfer combined 2014 The pronator quadratus muscle transfer combined with the Sauvé-Kapandji procedure was used to treat the distal radioulnar joint disorder in ten rheumatoid wrists for prevention against instability of the proximal ulnar stump. All patients were female with a mean age of 46.6 years. The mean follow-up time was 24.2 months. Postoperatively, supination increased in all patients with a mean of 50 degrees. Pain decreased significantly and none complained of prominence of the proximal ulnar stump in normal pronated position and during a tight grip. The wrist radiographs of both coronal and sagittal planes in normal and stress fisting views were used to evaluate the postoperative static and physiologic loaded stability of the proximal ulnar stump. It had shown this procedure provided good static proximal ulnar stump stability in both coronal and sagittal planes. However, in physiologic loaded condition, it was able to provide stability only in the sagittal plane.
24397123 [Effectiveness comparison of different tibial intramedullary nail guide rod in total knee 2013 Oct OBJECTIVE: To compare the effectiveness of the traditional center of tibial plateau as the entry point and digital technology in the design of intramedullary tibial nail point positioning method in total knee arthroplasty (TKA). METHODS: Between October 2011 and October 2012, 60 cases undergoing unilateral TKA and meeting the selection criteria were randomly divided into 2 groups: in group A (30 cases), the tibial plateau center as the entry point of tibial intramedullary positioning was used; in group B (30 cases), Mimics 10.01 software to simulate the guide rod point of tibial intramedullary positioning was used. There was no significant difference in gender, age, etiology, disease duration, sides, and preoperative knee range of motion, Hospital for Special Surgery (HSS) score, and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) between 2 groups (P > 0.05). Postoperative X-ray films were taken to measure the tibiofemoral angle and tibial angle; knee range of motion, and HSS and WOMAC scores were used to assess the activity of knee. RESULTS: The entry point of group B was located in front of the center of tibial plateau, which was inconsistent with the traditional entry point. The incision healed by first intention in all patients of 2 groups. The patients were followed up 6 to 12 months (mean, 8.6 months). The X-ray measurement at 1 week after operation showed no significant difference in tibiofemoral angle between 2 groups (t = -6.65, P = 0.72), but the anteroposterior and lateral tibial angles of group A were significantly lower than those of group B (P < 0.05). The knee range of motion, HSS score, and WOMAC score of 2 groups were significantly higher at 3 and 6 months after operation when compared with preoperative values (P < 0.05), and the values at 6 months were significantly increased than those at 3 months after operation (P < 0.05). HSS score and WOMAC score had no significant difference between 2 groups at 3 months after operation (P > 0.05), but the scores of group B were significantly higher than those of group A at 6 months (P < 0.05). The knee range of motion of group B was significantly better than that of group A at 3 months after operation (t = 2.13, P = 0.04), but no significant difference was found between 2 groups at 6 months (t = 0.58, P = 0.56). CONCLUSION: Compared with the traditional intramedullary guide rod insertion point positioning, digital individualized design of entry point positioning has the advantages of more accurate lower limb force line, better recovery of knee function, and earlier 90 degrees activities, but the long-term effectiveness needs further observation.
25267808 Late-onset methotrexate-induced pneumonitis with neutrophilia in bronchoalveolar lavage fl 2014 Sep 29 A 61-year-old woman being treated with methotrexate (MTX) 8-10 mg/week and prednisolone 2.5 mg/day for rheumatoid arthritis presented with a 1-week history of increasing fever and dry cough. The patient deteriorated with administration of antibiotics. Chest CT scan showed bilateral diffuse ground-glass opacities. Analysis of bronchoalveolar lavage fluid (BALF) revealed marked neutrophilia (65.2% of total cells). The specimen from transbronchial lung biopsy showed a non-specific interstitial pneumonia pattern. Following withdrawal of the MTX, her pulmonary infiltration, clinical symptoms and laboratory findings gradually improved. Therefore, she was diagnosed as having MTX-induced pneumonitis. Lymphocytosis in BALF has been identified as a characteristic of MTX-induced pneumonitis, particularly in late onset of this disease. However, the BALF in our patient was neutrophilic. Although neutrophilia in BALF of patients with drug-induced pneumonitis is usually associated with poor outcome, rare cases of good outcome do exist.
23792346 Relationship between rheumatoid arthritis activity and antithyroid antibodies. 2013 INTRODUCTION: Rheumatoid arthritis (RA) is known to be associated with a higher prevalence of antithyroid antibodies and autoimmune thyroid disease, but there have been few studies regarding the correlations between the presence of these antibodies and RA activity. OBJECTIVES: The aim of this study was to analyze the relationship between antithyroid antibody titers and selected parameters of RA activity. PATIENTS AND METHODS: A total of 75 consecutive hospitalized patients with RA were enrolled into the study. Levels of antithyroid peroxidase antibodies (aTPO), antithyroglobulin antibodies (aTG), and antithyrotropin receptor antibodies (aTSH-R) were measured. The analysis of disease activity was based on the disease activity score with 28-joint count (DAS28), duration of morning stiffness, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) and hemoglobin levels. RESULTS: Antithyroid antibodies were present in 13.3% of the patients (n = 10), aTPO in 9.3% (n = 7), aTG in 8% (n = 6), and aTPO and aTG in 4% (n = 3); aTSH-R was not detected in any of the patients. Significant positive correlations (P <0.05) were observed between aTPO and DAS28 (r = 0.35, P = 0.002), aTG and ESR (r = 0.25, P = 0.02), and aTG and CRP (r = 0.23, P = 0.04). There were significant differences in the mean DAS28 between the aTPO‑positive and aTPO‑negative groups (5.35; 95% confidence interval [CI], 4.39-6.3 vs. 4.12, respectively; 95% Cl, 3.81-4.43; P = 0.017) and between the aTG-positive and aTG-negative groups (5.65; 95% Cl: 4.64-6.67 vs. 4.11; 95% Cl: 3.81-4.41; P = 0.005; respectively). CONCLUSIONS: Our results suggest that RA activity may be associated with the presence of antithyroid antibodies. This finding could be useful in the clinical evaluation of RA patients.