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ID PMID Title PublicationDate abstract
29955927 The subjective components of the Disease Activity Score 28-joints (DAS28) in rheumatoid ar 2018 Oct To determine the contribution of fibromyalgia (FM) to the subjective components of the Disease Activity Score 28-joints (DAS28) in patients with rheumatoid arthritis (RA), and to analyse the discriminatory performance of the derived DAS28 patient-reported components (DAS28-P) to identify patients with fibromyalgic RA. Consecutive RA patients underwent clinical and clinimetric assessment. The DAS28-P index was derived from the components of the DAS28 scores by rearranging the DAS28-ESR formula. Patients were distinguished by the presence of FM. Student parametric t tests or Mann-Whitney non-parametric U tests were used to determine any between-group differences. Receiver operating characteristic (ROC) curve analysis was used to test the ability of the DAS28-P index to distinguish patients with RA and those with fibromyalgic RA. The study involved 292 RA patients (80.5% females, mean age 63 years) with a mean disease duration of 11.6 ± 8.5 years. Forty-three patients (14.7%) had concomitant FM, and significantly higher tender joint count (p < 0.001), pain numerical rating scale, global health status (p = 0.007), and DAS28 scores (p = 0.006) than those without FM. The DAS28-P values were also significantly higher in the patients with FM (0.68 ± 0.09 vs 0.58 ± 0.06; p < 0.001). The discriminatory power of the DAS28-P was very good (area under the ROC of 0.858, optimal cut-off value of 0.631). The presence of FM strongly influences the DAS28 results. The assessment of patient-reported components to the DAS28 through the DAS28-P can be a useful way to identify patients with fibromyalgic RA.
29530998 Clinical Significance of Myeloid-Related Protein 8/14 as a Predictor for Biological Treatm 2018 Jan OBJECTIVES: To investigate the serum level of Myeloid-Related Protein 8/14 complex (MRP8/14) and to predict and monitor the response to biologic treatment in rheumatoid arthritis (RA) patients. METHODS: Each patient underwent clinical examination and blood sampling for assessment of serum high-sensitivity C-reactive protein (hs-CRP) levels, erythrocyte sedimentation rate (ESR), rheumatoid factors (RF), anti-cyclic citrullinated protein antibodies (anti-CCP), and serum concentrations of MRP8/14 protein complexes (myeloid-related proteins, MRP8/14) were measured at baseline, and weeks 4 and 12 (after initiation of treatment). RESULTS: Serum MRP8/14 protein complex levels correlated with DAS28 and anti-CCP antibody. MRP8/14 protein complex levels decreased significantly after 12 weeks treatment with biological therapy: mono-rhTNFR-Fc active group. rhTNFR-Fc plus methotrexate (MTX) decreased MRP8/14 protein complex levels from 11839±1849 ng/ml to 5423±1130 ng/ml (p<0.01) a reduction of 54.2% compared with 32.9% in the rhTNFR-Fc group. CONCLUSIONS: MRP8/14 protein complex levels were increased in active stage RA patients. MRP8/14 levels were decreased with rhTNFR-Fc treatment, suggesting serum concentrations of MRP8/14 protein complex might be a promising biomarker to predict responses to biological therapy in active RA patients at baseline and could be used to monitor responses to treatment across different mechanisms of action.
28635117 Relationship Between Fish Consumption and Disease Activity in Rheumatoid Arthritis. 2018 Mar OBJECTIVE: To assess whether more frequent fish consumption is associated with lower rheumatoid arthritis (RA) disease activity scores among participants in an RA cohort. METHODS: We conducted a cross-sectional analysis using baseline data from participants in the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis cohort study. Frequency of fish consumption was assessed by a baseline food frequency questionnaire assessing usual diet in the past year. Multivariable, total energy-adjusted linear regression models provided effect estimates and 95% confidence intervals (95% CIs) for frequency of fish consumption (i.e., never to <1 time/month, 1 time/month to <1 time/week, 1 time/week, and ≥2 times/week) on baseline Disease Activity Score in 28 joints (DAS28) using the C-reactive protein (CRP) level. We also estimated the difference in DAS28-CRP associated with increasing fish consumption by 1 serving per week. RESULTS: Among 176 participants, the median DAS28-CRP score was 3.5 (interquartile range 2.9-4.3). In an adjusted linear regression model, subjects consuming fish ≥2 times/week had a significantly lower DAS28-CRP compared with subjects who ate fish never to <1 time/month (difference -0.49 [95% CI -0.97, -0.02]). For each additional serving of fish per week, DAS28-CRP was significantly reduced by 0.18 (95% CI -0.35, -0.004). CONCLUSION: Our findings suggest that higher intake of fish may be associated with lower disease activity in RA patients.
29575737 The Impact of Ultrasound on the Use and Efficacy of Intraarticular Glucocorticoid Injectio 2018 Aug OBJECTIVE: Intraarticular glucocorticoid injections are common in rheumatoid arthritis (RA) treatment. This study was undertaken to investigate whether ultrasound in combination with clinical examination is better than clinical examination alone at identifying joints that will benefit from intraarticular injections, and to compare the efficacy of ultrasound-guided versus palpation-guided procedures. METHODS: In the treat-to-target Aiming for Remission in Rheumatoid Arthritis: a Randomised Trial Examining the Benefit of Ultrasonography in a Clinical Tight Control Regimen (ARCTIC), patients with early RA were randomized 1:1 to follow-up with or without ultrasound. In addition to disease-modifying antirheumatic drugs, intraarticular glucocorticoids were used to treat inflamed joints. The distribution of injections was assessed in both study groups. The relationship of clinical and ultrasound findings at the time of injection with treatment efficacy was examined, with non-swollen joint at the next visit as the outcome measure. Treatment success was compared across study groups to evaluate ultrasound-guided versus palpation-guided procedures. RESULTS: More injections were administered in the ultrasound group than in the conventional strategy group (n = 770 versus 548), especially in intercarpal joints (n = 58 versus 5) and metatarsophalangeal joints (n = 200 versus 104). Injecting clinically swollen joints without power Doppler (PD) activity on ultrasound was not efficacious compared to not injecting (odds ratio [OR] 1.3; P = 0.59). Efficacy was best in swollen joints (OR 9.0; P = 0.001) and non-swollen joints (OR 8.4; P = 0.016) with moderate PD activity. Treatment success was similar for the ultrasound-guided and palpation-guided procedures. CONCLUSION: Our findings indicate that the efficacy of intraarticular glucocorticoid injections varies according to ultrasound findings at the time of injection, supporting the use of ultrasound as a tool to select joints that will benefit from intraarticular injections. However, ultrasound needle guidance was not superior to palpation guidance.
29725131 Interleukin-6: designing specific therapeutics for a complex cytokine. 2018 Jun Interleukin-6 (IL-6) is a pivotal cytokine with a diverse repertoire of physiological functions that include regulation of immune cell proliferation and differentiation. Dysregulation of IL-6 signalling is associated with inflammatory and lymphoproliferative disorders such as rheumatoid arthritis and Castleman disease, and several classes of therapeutics have been developed that target components of the IL-6 signalling pathway. So far, monoclonal antibodies against IL-6 or IL-6 receptor (IL-6R) and Janus kinases (JAK) inhibitors have been successfully developed for the treatment of autoimmune diseases such as rheumatoid arthritis. However, clinical trials of agents targeting IL-6 signalling have also raised questions about the diseases and patient populations for which such agents have an appropriate benefit-risk profile. Knowledge from clinical trials and advances in our understanding of the complexities of IL-6 signalling, including the potential to target an IL-6 trans-signalling pathway, are now indicating novel opportunities for therapeutic intervention. In this Review, we overview the roles of IL-6 in health and disease and analyse progress with several approaches of inhibiting IL-6-signalling, with the aim of illuminating when and how to apply IL-6 blockade.
29908080 Genotypes, phenotypes and treatment with immunomodulators in the rheumatic diseases. 2018 Sep The autoimmune rheumatological diseases rheumatoid arthritis (RA), spondyloarthritis (SpA) and systemic lupus erythematosus (SLE) are treated with conventional immunosuppressive agents and with modern biological immunomodulators. The latter group of medications have brought about a major change in our ability to control RA and SpA, with more modest results for SLE. The biologicals are very specific in their mechanisms of action, targeting one specific cytokine or one particular cellular marker. Because of this, their efficacy can readily be linked to a single immunomodulatory mechanism. This observation has fuelled hopes that the efficacy of these agents can be predicted at the individual level based on the patient's genetic predisposition, immunological profile or disease phenotype. Whilst the biologic therapies have improved the prospects for patients with these diseases very significantly, the hope that they could be targeted to the patient in an individualized manner has not completely born fruit. In this review, I will argue that we are witnessing important progress in this field, and that justified hope exists for true advances in precision medicine in the autoimmune diseases in the coming years.
29551687 Application of global metabolomic profiling of synovial fluid for osteoarthritis biomarker 2018 May 5 Osteoarthritis affects over 250 million individuals worldwide. Currently, there are no options for early diagnosis of osteoarthritis, demonstrating the need for biomarker discovery. To find biomarkers of osteoarthritis in human synovial fluid, we used high performance liquid-chromatography mass spectrometry for global metabolomic profiling. Metabolites were extracted from human osteoarthritic (n = 5), rheumatoid arthritic (n = 3), and healthy (n = 5) synovial fluid, and a total of 1233 metabolites were detected. Principal components analysis clearly distinguished the metabolomic profiles of diseased from healthy synovial fluid. Synovial fluid from rheumatoid arthritis patients contained expected metabolites consistent with the inflammatory nature of the disease. Similarly, unsupervised clustering analysis found that each disease state was associated with distinct metabolomic profiles and clusters of co-regulated metabolites. For osteoarthritis, co-regulated metabolites that were upregulated compared to healthy synovial fluid mapped to known disease processes including chondroitin sulfate degradation, arginine and proline metabolism, and nitric oxide metabolism. We utilized receiver operating characteristic analysis to determine the diagnostic value of each metabolite and identified 35 metabolites as potential biomarkers of osteoarthritis, with an area under the receiver operating characteristic curve >0.9. These metabolites included phosphatidylcholine, lysophosphatidylcholine, ceramides, myristate derivatives, and carnitine derivatives. This pilot study provides strong justification for a larger cohort-based study of human osteoarthritic synovial fluid using global metabolomics. The significance of these data is the demonstration that metabolomic profiling of synovial fluid can identify relevant biomarkers of joint disease.
29174794 Survivin improves the early recognition of rheumatoid arthritis among patients with arthra 2018 Jun OBJECTIVES: The aim of this study was to validate the use of survivin for preclinical recognition of rheumatoid arthritis (RA) among patients with unexplained arthralgia. METHODS: Serum levels of survivin and the arthritis-specific autoantibodies RF and ACPA were measured in total of 5046 patients with musculoskeletal complains during 12 consecutive months in Gothenburg and in Umeå. Among them, 303 arthralgia patients were identified and prospectively followed. RESULTS: After 48 months, 12.2% of the arthralgia patients developed RA. Most of RA cases had high serum survivin, which increased the relative risk for RA (RR = 5.90, p = 3 × 10(-7)). Combination of survivin with autoantibodies was present in only 4.6% of the arthralgia patients and increased further the risk of RA and shortened time to RA development. Presence of any single autoantibody in the survivin-negative patients was associated with a minor risk for RA and had RA-free survival similar to the reference group. CONCLUSION: This study shows that measurement of survivin in serum improves estimation of RA risk and prospectively predicts RA development in patients with arthralgia. Survivin may indicate a phase preceding autoantibody production.
29700991 A New Treatment Modality for Rheumatoid Arthritis: Combined Photothermal and Photodynamic 2018 Jul Rheumatoid arthritis (RA) is a worldwide inflammatory disease that seriously threatens human health and needs more effective treatment approaches. Near infrared (NIR) light can efficiently penetrate inflamed joints affected by RA, so phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), may provide new opportunities. In this work, the unique Cu(7.2) S(4) nanoparticles (NPs) are prepared for RA treatment enlightened by the fact that copper (Cu)-based nanomaterials can simultaneously serve as PTT agents and photosensitizers (for PDT). Meanwhile, Cu can promote ostogenesis and chondrogenesis. The Cu(7.2) S(4) NPs combined with NIR (808 nm, 1 W cm(-2) ) irradiation not only achieve better bone preservation, including higher bone mineral density (BMD) and bone volume/total volume, but also inhibit inflamed synovial invasion, cartilage erosion, and expression of proinflammatory cytokines in vivo. Moreover, the Cu(7.2) S(4) NPs can effectively kill clinical pathogenic Staphylococcus aureus and Escherichia coli to prevent bacterial infection during intra-articular injection. Therefore, the combined PTT and PDT using the multifunctional Cu(7.2) S(4) NPs could be a novel RA treatment modality with full potential.
29314556 Barriers and reinforcing factors to self-management behaviour in rheumatoid arthritis pati 2018 Jun OBJECTIVE: The aim of the present study was to explore the view of rheumatoid arthritis (RA) patients about the barriers and reinforcing factors in practising self-management behaviour (SMB). METHODS: This was a qualitative study based on directed content analysis of in-depth semi-structured interviews with 30 patients. The participants were selected using a purposeful sampling approach. The interviews continued until data saturation was reached. The study was conducted over 6 months in 2014-2015 at the Rheumatology Clinic of Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. RESULTS: Three main themes and 14 subthemes were extracted. The main themes included behavioural barriers, environmental barriers and reinforcing factors. The subthemes included lack of awareness; poor physician-patient relationship; lack of motivation; negative attitude and willingness; lack of time; cost; housing conditions and in-home equipment; negative social effects; social support; consequences of SMB; and comparing yourself with others. CONCLUSION: Behavioural and environmental barriers, as well as social support and outcomes of SMB were the most important barriers and reinforcing factors of SMB. Therefore, considering these factors in patients may help in designing programmes that attempt to reduce barriers and increase reinforcing factors, which ultimately result in higher levels of SMB and quality of life among patients.
28741973 Characteristics of functional impairment in patients with long-standing rheumatoid arthrit 2018 May OBJECTIVE: To explore the characteristics of functional impairment in patients with established rheumatoid arthritis (RA) based on the range of motion (ROM) of joints in a prospective observational study of RA patients undergoing joint surgery. METHODS: We collected data on demographics, Health Assessment Questionnaire Disability Index (HAQ-DI), and the ROM of large joints including the shoulder, elbow, wrist, hip, knee, and ankle. Associations between the ROM of each joint and disability in the eight HAQ-DI categories were determined using receiver operating characteristic (ROC) and logistic regression analyses. ROM cut-off values of each joint for the absence of disability in each HAQ-DI category were determined using ROC curves. RESULTS: A total of 460 patients were enrolled and analyzed in this study. Based on ROC analysis, the ROM of each joint was significantly associated with disability in each category. After adjusting for disease activity, age, and sex, shoulder abduction had the highest independent impact on disability in activity [cut-off: 139 degrees (OR: 5.26)], elbow flexion-extension in dressing [121 degrees (OR: 2.22)], wrist flexion-extension in reach [86 degrees (OR: 2.71)], hip flexion-extension in walking [126 degrees (OR: 3.42)], and knee flexion-extension in walking [134 degrees (OR: 2.97)]. CONCLUSIONS: Limited ROM of multiple joints was significantly associated with functional impairment in patients with long-standing RA. Motion in daily activity involves multiple joints, and at least two joints were independently involved in disability.
29668445 Pathobiochemical Mechanisms Relating Iron Homeostasis with Parameters of Inflammatory Acti 2018 Mar 1 AIM: To find the correlations between the parameters of iron homeostasis, inflammatory activity and autoimmune disorders in rheumatoid arthritis (RA). MATERIALS AND METHODS: The present study included 114 patients with RA and 42 healthy controls. We determined the parameters of iron homeostasis: serum iron, total iron binding capacity (TIBC), ferritin and soluble transferrin receptor (sTfR), the parameters of inflammatory activity: C-reactive protein (CRP), interleukin-6 (IL-6) and prohepcidin, and the parameters of autoimmune disorders: rheumatoid factor (RF), anti-cyclic citrullinated peptide (antiCCP) antibodies and DAS 28. RESULTS: The levels of sTfR, CRP, IL-6 and prohepcidin were significantly higher in RA patients than those in the controls and the level of serum iron was significantly lower in RA than that in the control group. Unlike the controls, in RA, there was a significant positive correlation of sTfR with the parameters of inflammatory activity (IL-6, prohepcidin, ESR) and with the parameters of autoimmune disorders (DAS 28, RF, antiCCP). A negative correlation of serum iron with sTfR was found only in RA patients. Prohepcidin positively correlated with the parameters of inflammation (CRP, ESR) and with the parameters for evaluation of autoimmune disorders (DAS 28 and RF) in the RA group. CONCLUSION: Our study shows that the simultaneous determination of the two parameters sTfR and prohepcidin is most informative for evaluation of the changes in iron homeostasis in RA. The increase of both parameters provides information for tissue iron deficiency (assessed by the level of sTfR), caused by the inflammation when prohepcidin is expressed.
29884223 Serum IL-33 level is associated with auto-antibodies but not with clinical response to bio 2018 Jun 8 Rotation or Change of Biotherapy After First Anti-TNF Treatment Failure for Rheumatoid Arthritis (ROC), registered 22 October 2009, NCT01000441.
29160727 A Review of Perioperative Complications of Outpatient Total Ankle Arthroplasty. 2018 Feb BACKGROUND: Total ankle arthroplasty (TAA) is commonly pursued for patients with painful arthritis. Outpatient TAA are increasingly common and have been shown to decrease costs compared to inpatient surgery. However, there are very few studies examining the safety of outpatient TAA. In this study, we retrospectively reviewed 65 consecutive patients who received outpatient TAA to identify complication rates. METHODS: The medical records of 65 consecutive outpatient TAA from October 2012 to May 2016 with a minimum 6-month follow-up were reviewed. All patients received popliteal and saphenous blocks prior to surgery and were managed with oral pain medication postoperatively. All received a STAR total ankle. Demographics, comorbidities, American Society of Anesthesiologists (ASA) class, and perioperative complications including wound breakdown, infection, revision, and nonrevision surgeries were observed. Mean follow-up was 16.6 ± 9.1 months (range, 6-42 months). RESULTS: There were no readmissions for pain control and 1 patient had a wound infection. The overall complication rate was 15.4%. One ankle (1.5%) had a wound breakdown requiring debridement and flap coverage. This patient thrombosed a popliteal artery stent 1 month postop. The 1 ankle (1.5%) with a wound infection occurred in a patient with diabetes, obesity, hypertension, and rheumatoid arthritis. CONCLUSION: This study demonstrates the safety of outpatient TAA. The combination of regional anesthesia and oral narcotics provided a satisfactory experience with no readmissions for pain control and 1 wound infection. The 1 wound breakdown complication (1.5%) was attributed to arterial occlusion and not outpatient management. LEVEL OF EVIDENCE: Level IV, retrospective case series.
29885551 Prealbumin, platelet factor 4 and S100A12 combination at baseline predicts good response t 2019 Mar OBJECTIVES: Tumour necrosis factor-alpha inhibitors (TNFi) are effective treatments for Rheumatoid Arthritis (RA). Responses to treatment are barely predictable. As these treatments are costly and may induce a number of side effects, we aimed at identifying a panel of protein biomarkers that could be used to predict clinical response to TNFi for RA patients. METHODS: Baseline blood levels of C-reactive protein, platelet factor 4, apolipoprotein A1, prealbumin, α1-antitrypsin, haptoglobin, S100A8/A9 and S100A12 proteins in bDMARD naive patients at the time of TNFi treatment initiation were assessed in a multicentric prospective French cohort. Patients fulfilling good EULAR response at 6 months were considered as responders. Logistic regression was used to determine best biomarker set that could predict good clinical response to TNFi. RESULTS: A combination of biomarkers (prealbumin, platelet factor 4 and S100A12) was identified and could predict response to TNFi in RA with sensitivity of 78%, specificity of 77%, positive predictive values (PPV) of 72%, negative predictive values (NPV) of 82%, positive likelihood ratio (LR+) of 3.35 and negative likelihood ratio (LR-) of 0.28. Lower levels of prealbumin and S100A12 and higher level of platelet factor 4 than the determined cutoff at baseline in RA patients are good predictors for response to TNFi treatment globally as well as to Infliximab, Etanercept and Adalimumab individually. CONCLUSION: A multivariate model combining 3 biomarkers (prealbumin, platelet factor 4 and S100A12) accurately predicted response of RA patients to TNFi and has potential in a daily practice personalized treatment.
30029649 A prospective cohort study measuring cost-benefit analysis of the Otago Exercise Programme 2018 Jul 20 BACKGROUND: Falls are one of the major health problems in adults with Rheumatoid Arthritis (RA). Interventions, such as the Otago Exercise Programme (OEP), can reduce falls in community dwelling adults by up to 35%. The cost-benefits of such a programme in adults with RA have not been studied. The aims of this study were to determine the healthcare cost of falls in adults with RA, and estimate whether it may be cost efficient to roll out the OEP to improve function and prevent falls in adults living with RA. METHODS: Patients with Rheumatoid Arthritis aged ≥18 years were recruited from four rheumatology clinics across the Northwest of England. Participants were followed up for 1 year with monthly fall calendars, telephone calls and self-report questionnaires. Estimated medical cost of a fall-related injury incurred per-person were calculated and compared with OEP implementation costs to establish potential economic benefits. RESULTS: Five hundred thirty-five patients were recruited and 598 falls were reported by 195 patients. Cumulative medical costs resulting from all injury leading to hospital services is £374,354 (US$540,485). Average estimated cost per fall is £1120 (US$1617). Estimated cost of implementing the OEP for 535 people is £116,479 (US$168,504) or £217.72 (US$314.34) per-person. Based on effectiveness of the OEP it can be estimated that out of the 598 falls, 209 falls would be prevented. This suggests that £234,583 (US$338,116) savings could be made, a net benefit of £118,104 (US$170,623). CONCLUSIONS: Implementation of the OEP programme for patients with RA has potentially significant economic benefits and should be considered for patients with the condition.
30119166 Novel drug delivery systems for NSAIDs in management of rheumatoid arthritis: An overview. 2018 Oct Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic joint inflammation which ultimately leads to severe disability and premature mortality. It has a global prevalence of around 1% with the incidence among women being 2-3 times more than in men. The pathogenesis of the disease involves preclinical RA, genetic factors, and environmental factors. The RA has no known cure and the primary aim of treatment remains to attain lowest possible disease activity and recovery if possible. The present review highlights the literature on the different treatment options available for the treatment of RA, their mechanisms of action, side effects, and novel drug delivery systems that are in use for drug administration with the main focus on novel drug delivery systems of non-steroidal anti-inflammatory drugs. Different classes of drugs such as corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) and disease modifying anti-rheumatic drugs (DMARDs), and biologics are discussed with examples of most widely used drugs among each class. Conventional drug therapy has many disadvantages like low solubility and permeability, poor bioavailability, degradation by gastrointestinal enzymes, first pass metabolism, food interactions, and toxicity. Novel drug delivery systems like microspheres, nanoparticles, dendrimers, liposomes, and so on are promising tools as they have been successful in overcoming the disadvantages associated with conventional drug delivery system. The present review squares the various novel drug delivery systems that have been explored for administering anti-rheumatic drugs and the advantages associated with these novel drug delivery systems in comparison to conventional drug delivery systems.
29109029 Transcriptional profile of human macrophages stimulated by ultra-high molecular weight pol 2018 Jan Osteolysis is a serious postoperative complication of total joint arthroplasty that leads to aseptic loosening and surgical revision. Osteolysis is a chronic destructive process that occurs when host macrophages recognize implant particles and release inflammatory mediators that increase bone-resorbing osteoclastic activity and attenuate bone-formation osteoblastic activity. Although much progress has been made in understanding the molecular responses of macrophages to implant particles, the pathways/signals that initiate osteolysis remain poorly characterized. Transcriptomics and gene-expression profiling of these macrophages may unravel key mechanisms in the pathogenesis of osteolysis and aid the identification of molecular candidates for therapeutic intervention. To this end, we analyzed the transcriptional profiling of macrophages exposed to ultra-high molecular weight polyethylene (UHMWPE) particles, the most common components used in bearing materials of orthopedic implants. Regulated genes in stimulated macrophages were involved in cytokine, chemokine, growth factor and receptor activities. Gene enrichment analysis suggested that stimulated macrophages elicited common gene expression signatures for inflammation and rheumatoid arthritis. Among the regulated genes, tumor necrosis factor superfamily member 15 (TNFSF15) and chemokine ligand 20 (CCL20) were further characterized as molecular targets involved in the pathogenesis of osteolysis. Treatment of monocyte cultures with TNFSF15 and CCL20 resulted in an increase in osteoclastogenesis and bone-resorbing osteoclastic activity, suggesting their potential contribution to loosening between implants and bone tissues. STATEMENT OF SIGNIFICANCE: Implant loosening due to osteolysis is the most common mode of arthroplasty failure and represents a great challenge to orthopedic surgeons and a significant economic burden for patients and healthcare services worldwide. Bone loss secondary to a local inflammatory response initiated by particulate debris from implants is considered the principal feature of the pathogenesis of osteolysis. In the present study, we analyzed the transcriptional profiling of human macrophages exposed to UHMWPE particles and identified a large number of inflammatory genes that were not identified previously in macrophage responses to wear particles. Our data provide a new insight into the molecular pathogenesis of osteolysis and highlights a number of molecular targets with prognostic and therapeutic implications.
28762476 Use of Early Clinical Trial Data to Support Thorough QT Study Waiver for Upadacitinib and 2018 May Exposure-response analyses of QT data from early-stage clinical studies represent a valuable tool to assess the QT prolongation potential for drugs in development in lieu of standalone thorough QT (TQT) studies. However, demonstrating adequate electrocardiogram assay sensitivity can be challenging in the absence of a positive pharmacological control. Upadacitinib is a Janus kinase 1 inhibitor currently being evaluated in phase III rheumatoid arthritis trials. Exposure-response analyses to evaluate the QT prolongation potential for upadacitinib from phase I trials and the utility of the effect of food on QTcF to demonstrate ECG assay sensitivity are presented. The analyses demonstrated no effect of upadacitinib on QT interval and confirmed the sensitivity of the ECG assay to detect the small QT shortening effect caused by food. Lack of bias from manual ECG adjudication was also demonstrated. These analyses supported requesting a waiver for the regulatory requirement for a dedicated thorough QT study for upadacitinib.
30187667 Long-term patient reported outcomes of elbow, wrist and hand surgery for rheumatoid arthri 2018 Sep AIM: A retrospective questionnaire survey was conducted to investigate the long-term outcomes of elbow, wrist and hand surgery for rheumatoid arthritis (RA). METHODS: One hundred and thirteen RA patients underwent primary elective elbow, wrist or hand surgery at our hospital between January 2002 and December 2003. To evaluate the outcomes at 10 years after surgery, the patient-reported outcomes were assessed using an original questionnaire that inquired about the site of treatment; the modified Stanford Health Assessment Questionnaire (mHAQ) was also used. RESULTS: Responses were obtained from 67 patients (98 sites). In the 10 years after surgery, the Disease Activity Score of 28 joint - erythrocyte sedimentation rate (4) and the modified Health Assessment Questionnaire scores of the patients showed significant improvement. Nearly 85% of patients were satisfied with the outcome at the surgical site. The most frequent reason for perceived improvement was 'pain relief' (all surgical sites). An 'improved appearance' was frequently reported after finger surgery and 'increased power' was frequently reported after wrist and thumb surgeries. With regard to elbow surgery, 30% of the patients were satisfied with the increase in motion and power. In contrast, approximately 20% of patients complained of decreased power around the surgical site after elbow and thumb surgeries. CONCLUSIONS: Our original patient-reported outcome assessment tool revealed that elbow, wrist and hand surgery provided long-lasting benefits in RA patients. While the efficacy differed in some of the surgical sites, pain relief was the most favorable effect. Altered medical therapy may also have impacted the patient-perceived outcomes of surgery at 10 years.