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

ID PMID Title PublicationDate abstract
29501867 Levetiracetam mitigates lipopolysaccharide-induced JAK2/STAT3 and TLR4/MAPK signaling path 2018 May 5 Levetiracetam (LEV), a novel anti-epileptic drug that has been demonstrated with an anti-inflammatory effect, but the exact mechanisms of its action remain to be fully defined. The present study aimed to evaluate the possible effects of LEV on lipopolysaccharides (LPS)-induced Janus kinase-signal transducers and activators of transcription (JAK/STAT) as well as toll-like receptor 4 (TLR4)/ mitogen activated protein kinase (MAPK) signaling pathways activation in adjuvant induced arthritis (AIA). Rats were allocated into normal control, three arthritic control groups: Complete Freund's Adjuvant (CFA) (0.4 ml/3days/12days), LPS (100 µg/kg/day), CFA+LPS, and three treated groups: CFA+LEV, LPS+LEV and CFA+LPS+LEV. LEV was administered in a dose 50 mg/kg/day for 15 day. After 28 days, tissue samples were collected for assessment of phosphorylated JAK2, STAT3, TLR4, MAPK and cathepsin K quantitative expression in synovium. Additionally, Serum samples were used for biochemical evaluation of interleukin-6 (IL-6), interleukin-1beta (IL-1B), LPS, anti-citrullinated protein antibody (ACPA) and 8-hydroxydeoxyguanosine (8-OHdG). Histopathological and macroscopical examinations of joints were also performed to support our study. Results indicated that LEV exerted its anti-inflammatory effect through inhibiting LPS-dependent phosphorylation of JAK2/STAT3 signaling. It significantly suppressed TLR4 and MAPK expressions, thereby decreasing release of inflammatory cytokines IL-1β, IL-6.LEV exhibited a potent inhibitory effect on cathepsin K and 8-OHdG parallel to confirmatory histopathological and macroscopical findings. In conclusion, LEV has a powerful therapeutic effect on adjuvant induced arthritis in rats and its mechanisms are strongly related to inhibiting excessive activation of JAK2-STAT3 and TLR4 pathways. This may add a new approach for treatment of RA.
29705475 The effects of reflexology on pain and sleep deprivation in patients with rheumatoid arthr 2018 May OBJECTIVE: This study was intended to examine the effect of foot reflexology on RA patients' pain and sleep quality. METHODS: This is a randomized controlled trial and was held at the "Rheumatology Follow-up Polyclinic" in Turkey between January-July 2015. A total of 60 patients were included in the research. A sociodemographic data form, the Pittsburgh Sleep Quality Index (PSQI) and the Visual Analogue Scale (VAS) were used. Foot Reflexology was administered to the experimental group. RESULTS: The research found that the pain scores of the experimental group were statistically more significant than those of the control group (p < .01). The experimental group's average pain was reduced by the six weeks of foot reflexology. The total PSQI score of the experimental group was lowered. CONCLUSIONS: Foot reflexology is a non-pharmacological nursing intervention that may reduce the pain and sleep deprivation symptoms of RA patients.
29927104 Affinity Maturation Drives Epitope Spreading and Generation of Proinflammatory Anti-Citrul 2018 Dec OBJECTIVE: Rheumatoid arthritis (RA) is characterized by the presence of anti-citrullinated protein antibodies (ACPAs); nevertheless, the origin, specificity, and functional properties of ACPAs remain poorly understood. The aim of this study was to characterize the evolution of ACPAs by sequencing the plasmablast antibody repertoire at serial time points in patients with established RA. METHODS: Blood samples were obtained at up to 4 serial time points from 8 individuals with established RA who were positive for ACPAs by the anti-cyclic citrullinated peptide test. CD19+CD3-IgD-CD14-CD20-CD27+CD38++ plasmablasts were isolated by single-cell sorting and costained with citrullinated peptide tetramers to identify ACPA-expressing plasmablasts. Cell-specific oligonucleotide barcodes were utilized, followed by large-scale sequencing and bioinformatics analysis, to obtain error-corrected, paired heavy- and light-chain antibody gene sequences for each B cell. RESULTS: Bioinformatics analysis revealed 170 persistent plasmablast lineages in the RA blood, of which 19% included multiple isotypes. Among IgG- and IgA-expressing plasmablasts, significantly more IgA-expressing than IgG-expressing persistent lineages were observed (P < 0.01). Shared complementarity-determining region 3 sequence motifs were identified across subjects. A subset of the plasmablast lineages included members derived from later time points with divergent somatic hypermutations that encoded antibodies that bind an expanded set of citrullinated antigens. Furthermore, these recombinant, differentially mutated plasmablast antibodies formed immune complexes that stimulated higher macrophage production of tumor necrosis factor (TNF) compared to antibodies representing earlier time point-derived lineage members that were less mutated. CONCLUSION: These findings demonstrate that established RA is characterized by a persistent IgA ACPA response that exhibits ongoing affinity maturation. This observation suggests the presence of a persistent mucosal antigen that continually promotes the production of IgA plasmablasts and their affinity maturation and epitope spreading, thus leading to the generation of ACPAs that bind additional citrullinated antigens and more potently stimulate macrophage production of TNF.
30657070 Evaluation of the safety and satisfaction of rheumatic patients with accelerated inflixima 2018 Aug 3 INTRODUCTION: Infliximab infusion generally occurs in 2-4 h. Recent studies have suggested the possibility of accelerated infusion (1 h) of this drug. OBJECTIVE: To evaluate the safety of accelerated infliximab infusion in patients with rheumatic diseases. In addition, patient satisfaction was also assessed. METHODS: A prospective, single-center, non-randomized study with 34 patients with rheumatic diseases was conducted from July to November 2016. Patients with the following were excluded: history of allergic reaction to biologics, asthma or severe atopy. All patients previously received a 2- to 3-h infliximab infusion. The infusion rate was accelerated to 1 h, and premedication was excluded. The infusion was monitored in all patients. RESULTS: A total of 34 patients were included in the study [rheumatoid arthritis (n = 16), ankylosing spondylitis (n = 15), psoriatic arthritis (n = 2) and enteropathic arthropathy (n = 1)], with an average age of 48.7 ± 18.6 years; 55.5% of the patients were female, and 29.4% were white. The duration of disease was 9.5 ± 9.2 years, and the duration of infliximab use was 38.9 ± 27.6 months, with a mean dose per infusion of 414.2 ± 158.1 (range, 200-800) mg. The mean infliximab infusion time prior to the study was 2.2 ± 0.4 h. A total of 6 (17.6%) patients received premedication. The premedication was suspended. There were no adverse effects during or after infusion. Ninety-seven percent of the patients and 100% of the health workers were satisfied with the accelerated infusion. CONCLUSION: Our data support the safe use of accelerated infliximab infusion in rheumatic patients, with high satisfaction among patients and health workers.
30167920 MiRNA-126 expression inhibits IL-23R mediated TNF-α or IFN-γ production in fibroblast-li 2018 Dec Both miR-126 and IL-23R affect rheumatoid arthritis (RA) procession. This study aimed to investigate the association of miR-126 and IL-23R and the possible modulation of miR-126 to RA pathogenesis. Serum, synovial tissue and synovial fluid were collected from patients with RA, and expression of miR-126, IL-23R, TNF-α and IFN-γ were detected. Fibroblast-like synoviocytes (FLS) was established using a collagen-induced arthritis mice model. The expression of miR-126 was manual intervened using pro-miR-126 and anti-miR-126 encoding lentivirus plasmids, or miR-126 agonists and corresponding negative controls. MiR-126 expression was inhibited in RA patients when compared with controls (P < 0.05). TNF-α and IFN-γ production and IL-23R expression were significantly upregulated in RA patients when compared to controls (P < 0.05). In pro-miR-126 treated FLS cells, the administration of pro-miR-126 plasmids upregulated miR-126, but inhibited IL-23R, TNF-α and IFN-γ expression or production. Moreover, the miR-126 agonist reversed the effects of the anti-miR-126 plasmid on FLS. These results revealed that miR-126 negative regulated the expression of IL-23R, TNF-α and IFN-γ. These results suggest the key impact of miR-126 on RA procession. Moreover, pro-miR-126 might be explored to be a potential therapy for RA.
29465354 Self-reported childhood maltreatment, lifelong traumatic events and mental disorders in Am 2018 Jul OBJECTIVES: Psychological stress is thought to play a major role in the development and exacerbation of autoimmune diseases in general, as well as in rheumatoid arthritis (RA) in particular. The aims of the current study are to compare retrospective self-reports of childhood maltreatment and lifetime major life/traumatic experiences of American and Israeli RA patients, using standardised instruments, while adjusting for concomitant mental disorders and psychological distress, in order to rule out their part in the subjective reports, thus addressing the trans-cultural robustness of the association between childhood maltreatment, traumatic experiences and RA. METHODS: RA patients at the participating study centres were recruited by their physicians, both in Israel and the USA. Patients filled out questionnaires regarding demographic data, disease activity, psychological distress, potential anxiety and potential depression. In addition, patients answered questions regarding pain and childhood maltreatment. RESULTS: 83 RA patients were recruited in the US and 23 patients in Israel. The comparison of CTQ-subscales between the US and Israeli cohorts showed significant differences between the groups only in the subscales of emotional neglect (US 10.30±5.05, Israeli 22.67±3.68, p<0.05) and emotional abuse (US 10.46±5.77, Israeli 7.13±4.84, p<0.05). 87% of Israeli patients had severe emotional neglect. Severe emotional abuse was associated with probable depression (OR 7.778, CI [1.907-31.716]). Using Pain Disability Index (PDI) score, Americans reported more pain during sexual activity than Israelis (US PDI Score 5.64±3.70. Israeli 3.16±3.86, p<0.05). PDI score was also associated with a previous traumatic event (36.89±18.57 vs. 16.82±14.85, p<0.05). CONCLUSIONS: A high degree of similarity was demonstrated between American and Israeli populations of RA patients, regarding psychological stressors and previous traumatic events. As expected, the results indicated a link between emotional abuse and depression in these patients. In addition, a previous traumatic event was associated with more significant pain. Physicians caring for RA patients should be vigilant regarding the possible association with childhood adversity and should consider appropriate consultations when indicated. In addition, while dealing with pain management in RA patients, physicians should keep in mind the possible contribution of distant childhood adversity.
30243154 Side effects of methotrexate therapy for rheumatoid arthritis: A systematic review. 2018 Oct 5 Methotrexate (MTX) is used as an anchor disease-modifying anti-rheumatic drugs (DMARDs) in treating rheumatoid arthritis (RA) because of its potent efficacy and tolerability. MTX benefits a large number of RA patients but partially suffered from side effects. A variety of side effects can be associated with MTX when treating RA patients, from mild to severe or discontinuation of the treatment. In this report, we reviewed the possible side effects that MTX might cause from the most common gastrointestinal toxicity effects to less frequent malignant diseases. In order to achieve regimen with less side effects, the administration of MTX with appropriate dose and a careful pretreatment inspection is necessary. Further investigations are required when combining MTX with other drugs so as to enhance the efficacy and reduce side effects at the same time. The management of MTX treatment is also discussed to provide strategies for occurred side effects. Thus, this review will provide scholars with a comprehensive understanding the side effects of MTX administration by RA patients.
30054716 Concomitant use of intravenous methylprednisolone to increase retention rate of abatacept 2018 Oct To investigate whether concomitant use of intravenous methylprednisolone (IVMP) with Abatacept (ABA) contributes to earlier remission and higher drug retention rates. This was a retrospective cohort study to assess the retention rate of ABA in rheumatoid arthritis (RA) patients treated at a single center in Japan from January 2010 to May 2017. Patients were divided into an ABA monotherapy group and ABA IVMP group. IVMP (40 mg) was administered with the first three consecutive doses of ABA. ABA retention rates were evaluated using Kaplan-Meier analysis. Hazard ratios for the drug retention rate were also calculated as the sensitivity analysis. A total of 59 seropositive RA patients were analyzed. Twelve patients were treated with ABA IVMP, and 47 patients were treated with ABA monotherapy. The overall ABA retention rate was 76.3% at 24 weeks. The retention rates were 91.7 and 72.3% in the ABA IVMP and ABA monotherapy groups, respectively. Log-rank analysis revealed no statistical difference between the two groups (p = 0.17). The sensitivity analysis showed that the hazard ratio of IVMP was 2.9-3.7 in three models, although there was no statistical significance. Safety analysis revealed that no patients discontinued ABA because of adverse events in the ABA IVMP group, while 7/47 (14.9%) discontinued the drug in the ABA monotherapy group. In this real life study, ABA, concomitantly used with IVMP, showed numerically higher retention rates without additional safety signals, although there was no statistical significance. Concomitant use of IVMP may help RA patients achieve earlier remission.
29494666 Variables associated with subclinical atherosclerosis in a cohort of rheumatoid arthritis 2018 OBJECTIVE: To advance the study of variables associated with subclinical atherosclerosis in rheumatoid arthritis (RA) with special consideration for the degree of disease activity, age and gender. METHODS: The carotid intima-media thickness (cIMT) and the presence of carotid atherosclerotic plaques along with clinical and biochemical characteristics were determined in 214 RA patients. RESULTS: Adjusted analysis reveals that men had a 0.059 mm significantly increased cIMT compared with women (p = 0.001; R2 = 3.8%) and that age was associated with cIMT (β = 0.0048 mm; p = 0.0001; R2 = 16%). Interestingly, we observed a significant interaction between gender and age. Thus, the effect of age on cIMT was significantly increased (12%) in men compared with women (p-value for interaction term = 0.041). Moreover, adjusted multivariable linear regression analysis revealed that disease activity score (DAS28) was significantly associated with cIMT in women (β = 0.021; p = 0.018: R2 = 0.03) but not men. In particular, women with high disease activity had a 0.079 mm increased cIMT compared with women in remission (p = 0.026). In addition, men in remission had a 0.134 mm increased cIMT compared with women in remission (p = 0.003; R2 = 8.7%). Active patients did not exhibit differences in cIMT values. Furthermore, 43% of patients presented carotid plaques. The variables independently associated with carotid plaques were age, smoking, health assessment questionnaire, erythrocyte sedimentation rate and rheumatoid factor (p<0.0001; R2 = 46%). CONCLUSION: In our cohort of patients with RA, DAS28 and age are differentially associated with cIMT in men and women. Our findings could explain the contradictory results that have previously been published in the literature.
30241955 Efficacy and Safety of Combined Therapy With Synthetic Disease-modifying Antirheumatic Dru 2020 Sep OBJECTIVE: 1) To systematically and critically review the evidence of combined therapy with synthetic disease-modifying antirheumatic drugs (DMARD) in rheumatoid arthritis (RA); 2) To design practical recommendations on their use. METHODS: A systematic literature review (SLR) was performed with a sensitive bibliographic search strategy in Medline, EMBASE and Cochrane Library. We selected randomized clinical trials that analyzed the efficacy and/or safety of 1) combined therapy of synthetic compared with sequential therapy of synthetic DMARD in early RA; and 2) combination of methotrexate+leflunomide or triple therapy with synthetic DMARD in established RA refractory to synthetic DMARD. Two reviewers made the first selection by title and abstract and 11 performed the selection after detailed review of the articles and data collection. The quality of the studies was evaluated with the Jadad scale. Based on the results, related recommendations were agreed upon in a nominal group meeting. RESULTS: Ultimately, no articles were included in the SLR. The analysis of the reviewed articles demonstrated the effectiveness of the treatment with synthetic DMARD following a "treat to target" strategy in early RA patients, and of combination therapy of synthetic DMARD in established RA refractory to synthetic DMARD. This resulted in 6 recommendations concerning combination therapy with synthetic DMARD. CONCLUSIONS: These recommendations aim to facilitate decision-making with the use of combined therapy with DMARD in RA.
30227885 Effects of a 15-month anti-TNF-α treatment on plasma levels of glycosaminoglycans in wome 2018 Sep 18 BACKGROUND: In this study, the effect of 15-month anti-tumor necrosis factor alpha (TNF-α) treatment on circulating levels of plasma sulfated glycosaminoglycans (GAGs) and the nonsulfated GAG hyaluronic acid (HA) in female rheumatoid arthritis (RA) patients was assessed. METHODS: Plasma was obtained from healthy subjects and RA women treated with TNF-α antagonists (etanercept or adalimumab or certolizumab pegol) in combination with methotrexate. GAGs were isolated from plasma samples using ion exchange low-pressure liquid chromatography. Total sulfated GAGs were quantified using a hexuronic acid assay. Plasma levels of keratan sulfate (KS) and HA were measured using immunoassay kits. RESULTS: Total sulfated GAGs and HA levels were higher in female RA patients before treatment in comparison to healthy subjects. KS levels did not differ between RA women and controls. Anti-TNF-α treatment resulted in normalization of plasma total GAG and HA levels in RA patients, without any effect on KS levels. CONCLUSIONS: Our results suggest that anti-TNF-α therapy has a beneficial effect on extracellular matrix remodeling in the course of RA.
29675950 Risk factors for red blood cell alloimmunization in the Recipient Epidemiology and Donor E 2018 Jun Despite the significance of red blood cell (RBC) alloimmunization, the lack of standardized registries in the US has prevented the completion of large studies. Data from 3·5 years of the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) recipient database, containing information from 12 hospitals, were studied. A RBC alloantibody responder had an antibody identified at any point during the study, and a non-responder had a negative antibody screen at least 15 days post-RBC transfusion. Demographics, blood type, ICD9/10 codes, and other potential correlates were evaluated. Of 319 177 (2·07%) screened patients, 6597 had a total of 8892 clinically significant RBC alloantibodies identified, with 75% being in the Rh or Kell families. Alloimmunization was more common in females (2·38%) than males (1·68%), and in RhD negative (2·82%) than RhD positive (1·94%) patients. Age, sex, RhD status and race were associated with being a responder, and certain diagnoses (including sickle cell disease or trait, systemic lupus erythematosus, rheumatoid arthritis and myelodysplastic syndrome) were more common among responders than non-responders. Data collected in this multi-centre recipient database provide the largest RBC alloimmunized patient cohort studied in the US, with previously known demographic and disease associations of responder status confirmed, and new associations identified.
29129008 High levels of oxidized fatty acids in HDL are associated with impaired HDL function in pa 2018 Mar The objective of this study was to evaluate oxidation products of arachidonic acid and linoleic acid in lipoproteins and synovial fluid (SF) from patients with active rheumatoid arthritis (RA) compared to non-RA controls. High-density lipoproteins (HDL) and low-density lipoproteins (LDL) were isolated from plasma using fast protein liquid chromatography and HDL was isolated from SF using dextran sulfate precipitation. 5-Hydroxyeicosatetraenoic acid (HETE), 12-HETE, 15-HETE, 9 hydroxyoctadecadienoic (HODE), and 13-HODE levels were measured in HDL, LDL, and SF by liquid chromatography-tandem mass spectrometry. HDL's anti-inflammatory function, cholesterol levels, myeloperoxidase (MPO) and paraoxonase 1 (PON1) activities were determined as previously. 5-HETE, 15-HETE, 9-HODE, and 13-HODE levels were significantly increased in HDL and LDL from patients with active RA (n = 10) compared to healthy controls (n = 8) and correlated significantly with measures of systemic inflammation, particularly in HDL (r = 0.65-0.80, p values < 0.004). Higher HETES and HODES in HDL were also significantly correlated with impaired HDL function as measured by the HDL inflammatory index (HII) (r = 0.54-0.58; p values < 0.03). 15-HETE levels and MPO activity were higher in RA SF (n = 10) compared to osteoarthritis (OA) SF(n = 11), and HDL from RA SF had worse function compared to OA SF HDL (HII = 2.1 ± 1.9 and 0.5 ± 0.1), respectively (p < 0.05). Oxidation products of arachidonic acid and linoleic acid are increased in HDL and LDL from patients with active RA compared to healthy controls, and are associated with worse anti-oxidant function of HDL. These results suggest a potential mechanism by which oxidative stress from active RA increases oxidized fatty acids in HDL, promoting HDL dysfunction, and thereby increasing atherosclerotic risk.
30284004 Arthroscopic synovectomy of the knee joint for rheumatoid arthritis. 2019 Aug OBJECTIVE: To investigate the effect of knee arthroscopic synovectomy (AS) on the disease activity, quality-of-life (QoL), and the functional status of patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: A retrospective analysis was conducted on the outcomes of AS performed on 138 RA patients; pre-surgery assessments were done using Disease Activity score (DAS 28) and Routine Assessment of Patient Index Data З (RAPID-3) on а multidimensional health-assessment questionnaire for disease activity, EuroQol-5D (EQ-5D) and the Short-Form Medical Outcomes Study (SF-36) for quality of life, and the Health Assessment Questionnaire (HAQ) for functional status. The pain response to SA was measured by а visual analogue score (VAS) and the Knee Society Score (KSS). RESULTS: All parameters assessed in the study showed significant positive changes: the activity of the disease decreased, and patients' functional status and QoL improved. CONCLUSION: AS is effective treatment for recurrent synovitis of the knee in RA patients. This technique improves the functional status of patients and their quality of life and reduces the activity of the disease.
30554233 Efficacy and Safety of 22-Oxa-Calcitriol in Patients with Rheumatoid Arthritis: A Phase II 2018 Dec 16 BACKGROUND Calcitriol (1 alpha, 25-dihydroxy vitamin D3) is a good vitamin D supplement but can cause hypercalcemia. Whereas, 22-oxa-1 alpha, 25-dihydroxy vitamin D3 (22-oxa-calcitriol) has less hypercalcemic activity than calcitriol and is reported to be effective for cell-proliferative diseases. The objective of the study was to compare renal function and blood tests of arthritis patients receiving calcitriol supplements with those receiving 22-oxa-calcitriol supplements. MATERIAL AND METHODS A total of 369 patients with clinically confirmed rheumatoid arthritis were included in this phase II trial. Patients received lactose powder (the placebo group, n=123), 50 000 IU/week of 22-oxa-calcitriol (the treatment group, n=123), or 50 000 IU/week of calcitriol (the control group, n=123) for 6 weeks. At the time of enrollment and after 6 weeks of supplementation, renal function tests, blood tests, and secondary outcome measures were evaluated. One-way ANOVA and the chi-squared test for independence were performed for continuous data and constant data at a 95% of confidence level. RESULTS Both 22-oxa-calcitriol and calcitriol successfully decreased swollen joints in patients with rheumatoid arthritis, and both improved Health Assessment Questionnaire Disease Activity Index scores and serum vitamin D levels. The intensity of improvement of serum vitamin D levels in both groups was the same (P<0.0001, q=0.24); however, calcitriol caused hypercalcemia (P<0.0001, q=12.59). CONCLUSIONS This study found that 22-oxa-calcitriol was a good option for vitamin D supplementation in rheumatoid arthritis patients.
30482092 Screening for cognitive dysfunction in systemic lupus erythematosus: the Montreal Cognitiv 2019 Jan BACKGROUND: Cognitive dysfunction (CD) is among the most common neuropsychiatric manifestations of systemic lupus erythematosus (SLE). Traditional neuropsychological testing and the Automated Neuropsychologic Assessment Metrics (ANAM) have been used to assess CD but neither is an ideal screening test. The Montreal Cognitive Assessment Questionnaire (MoCA) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) are brief and inexpensive tests. This study evaluated the MoCA and IQCODE as screening tools. METHODS: SLE patients fulfilling American College of Rheumatology (ACR) classification criteria were evaluated using the ANAM as the reference standard. The performance characteristics of the MoCA and IQCODE were assessed in comparison with normal controls (NCs) and rheumatoid arthritis (RA) patients. Four different definitions of CD were utilized. RESULTS: In total, 78 patients were evaluated. MoCA and ANAM scores were significantly correlated ( r = 0.51, p < 0.001). At the optimal cutoff, the sensitivity of the MoCA was ≥ 90% (depending on definition of CD) vs RA patients and ≥83% vs NCs. ANAM and IQCODE scores did not correlate ( p = 0.8152). IQCODE sensitivities were low for both RA patients and NCs regardless of definition and cutoff used. CONCLUSION: The MoCA appears to be a promising and practical screening tool for identification of patients with SLE at risk for CD.
30840564 Indications for primary rotating-hinge total knee arthroplasty. Is there consensus? 2018 Sep The use of rotating-hinge systems in total knee arthroplasty is most often seen in revision setting where excessive bone loss, ligamentous instability and/ or extensor mechanism dysfunction may necessitate an increased level of component constraint. However, this implant type is also being increasingly used in the primary setting. The aim of this study is to review literature concerning the use of third generation rotating-hinge devices focusing on the indications for primary cases. Literature was searched for following search terms: total knee arthroplasty, primary indication, constraint, rotating hinge knee, knee prosthesis, hinged knee, total knee replacement. Additional papers were identified by screening references and similar articles. All papers dealing with first or second generation rotating-hinge implants and revision cases were discarded. After conducting a large literature search, we concluded that third generation rotating-hinge implants should be considered in limited indications in which ligamentous tibiofemoral instability is the core indication.
29925168 [The efficacy of immunoadsorption with Infliximab theraepy on the modulation of disease ac 2018 Jun 19 Objective: To evaluated the efficacy of additional immunoadsorption therapy (2 times) besides infliximab (IFX) ondisease remission in patients with severe rheumatoid arthritis (RA). Methods: 90 patients with serve RA were included in this study.There were 43 patients in the control group who were treated with IFX 3 mg/kg+ methotrexate (MTX) therapy, and other 47 patients were experimental group, who were previous given 2 times additional immunoadsorption therapy before IFX 3 mg/kg+ MTX therapy.IFX 3 mg/kg was infused at weeks 0, 2, 6, 14, 22 and 30.Age, sex ration, mean disease duration and core index of disease activity in two treatment groups were collected at weeks 0, 2, 6 and 30 weeks to compare the efficacy and safety of combined immunosorbent therapy in the treatment of severe RA. Results: The baseline age, sex ration and core indexes of disease activity were comparable between the two treatment groups (P>0.05). After treatment, the core indexes of disease activity of all patients decreased significantly compared with their baseline levels (P<0.05) and the difference of sustainable maintenance to 30 weeks (P<0.05). After 2 and 6 weeks of treatment, patients' ACR20 remission rates of the experimental group were 46.81% and 68.08%, significantly higher than the control group; after 30 weeks of treatment, patients' ACR20 remission rates of the experimental group was more than 90%, while the number was 79.07% in the control group.At the same time DAS28-ESR clinical remission and low disease activity also reached 72.34% in the experimental group, higher than the control group(P<0.05). Conclusion: Additional immunoadsorption therapy can rapid relive the disease activity of serve RA patients, and the remission rate of 30W was significantly higher than only IFX treatment.
29273217 Characterizing Autoimmune Disease-associated Diffuse Large B-cell Lymphoma in a SEER-Medic 2018 Feb BACKGROUND: Severe immune dysregulation such as seen in autoimmune (AI) disease is known to act as a significant risk factor for diffuse large B-cell lymphoma (DLBCL). However, little is known about the demographics or clinical outcomes of DLBCL that arises in the setting of AI disease. PATIENTS AND METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database for patients with a diagnosis from 1999 to 2009 linked to their Medicare claims data through 2011 to characterize the presentation, treatment, and survival patterns in DLBCL patients, including those with rheumatoid arthritis, systemic lupus erythematosus (SLE), Sjögren syndrome, and other B-cell-mediated AI diseases. We examined the baseline clinical characteristics for patients with B-cell-mediated AI disease, plotted the overall survival and lymphoma-related survival (LRS) for these groups, and compared the median survival times. RESULTS: Patients with DLBCL and AI disease were more commonly female. However, patients with DLBCL and rheumatoid arthritis, SLE, Sjögren syndrome, or other B-cell AI diseases did not differ from other DLBCL patients in any other baseline presenting features and received similar first-line treatment. A trend toward decreased LRS was seen in patients with SLE and DLBCL compared with all other groups, but this difference was not statistically significant in this cohort. CONCLUSION: In the present retrospective claims-based cohort of older patients with DLBCL, concomitant AI disease was uncommon and was more likely to occur in female DLBCL patients, which likely reflects the greater incidence of AI disease in women. The possibility of lower LRS for SLE patients should be explored in future studies.
29854762 Suppression of Th1 and Th17 Responses and Induction of Treg Responses by IL-18-Expressing 2018 OBJECTIVES: IL-18 is a proinflammatory cytokine with multiple immunoregulatory properties. We studied the effect of IL-18 gene therapy on the development of murine collagen-induced arthritis (CIA). METHODS: Plasmid pCAGGS-IL-18 along or in combination with IL-10 or IL-4 was administered to CIA mice. The incidence and severity of arthritis of the paws were determined by a visual scale. Joint destruction was determined by histology. The levels of a panel of cytokines and transcription factors in the synovium were determined by reverse transcription polymerase chain reaction and quantitative RT-PCR. Quantitative RT-PCR was employed to detect the mRNA expression of TLRs and their pathway on the surface of DCs. RESULTS: IL-18 gene therapy had no therapeutic effect on CIA mice. Additional coadministration with low dosage of recombinant IL-4 ameliorated the disease progression. Histopathological examination of the joints showed intact cartilage surface in IL-18 gene combined with IL-4-treated mice. The synovium of IL-18 gene combined with rIL4-treated mice had lower expression of TNF-α, IFN-γ, and IL-17 and higher expression of IL-10. The mechanism of this response appeared to involve modulation of transcription factors FoxP3 and GATA-3. The DCs in the spleen and lymph nodes of IL-18 gene combined with rIL4-treated mice had lower expression of TLR2, MyD88, and NF-kB. CONCLUSIONS: Our findings indicate that pIL-18 gene combined with IL-4 ameliorates arthritis in the CIA mouse by suppression of Th1 and Th17 cytokines and increasing expression of FoxP3 and GATA-3. The plasmid backbone and multiple immunoregulatory properties of IL-18 appear to play a major role in the pIL-18 coadministration with rIL-4-mediated immunomodulation of arthritis through blocking the TLR2/MyD88/NF-kappa B signaling pathway.