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ID PMID Title PublicationDate abstract
28339004 Cyclocurcumin, a curcumin derivative, exhibits immune-modulating ability and is a potentia 2017 May The control and treatment of rheumatoid arthritis is a challenge in today's world. Therefore, the pursuit of natural disease-modifying antirheumatic drugs (DMRDs) remains a top priority in rheumatology. The present study focused on curcumin and its derivatives in the search for new DMRDs. We focused on prominent p38 mitogen-activated protein (MAP) kinase p38α which is a prime regulator of tumor necrosis factor-α (TNF-α), a key mediator of rheumatoid arthritis. In the present study, we used the X-ray crystallographic structure of p38α for molecular docking simulations and molecular dynamic simulations to study the binding modes of curcumin and its derivatives with the active site of p38α. The ATP-binding domain was used for evaluating curcumin and its derivatives. Molecular docking simulation results were used to select 4 out of 8 compounds. These 4 compounds were simulated using GROMACS molecular simulation platform; the results generated were subjected to molecular mechanics-Poisson Boltzmann surface area (MM-PBSA) calculations. The results showed cyclocurcumin as a potential natural compound for development of a potent DMRD. These data were further supported by inhibition of TNF-α release from lipopolysaccharide (LPS)-stimulated human macrophages following cyclocurcumin treatment.
29375375 Single- and Multiple-Dose Trials to Determine the Pharmacokinetics, Safety, Tolerability, 2017 Background and objectives: Ginsenoside compound K (CK) is a candidate drug for rheumatoid arthritis therapy. The objective of this study was to investigate the pharmacokinetic properties, safety and tolerability of CK. Methods: In randomized, double-blind trials, 76 healthy Chinese subjects received 1 of 7 single oral doses (25, 50, 100, 200, 400, 600, 800 mg) of CK or placebo under fasting condition, and another 36 subjects received repeated oral doses (100, 200, or 400 mg) of CK or placebo for up to 9 days a week after a corresponding single dose, after breakfast. Both sexes were equally represented in the two trials. Pharmacokinetic parameters of CK and its metabolite 20(S)-protopanaxadiol (PPD) were calculated and statistically analyzed according to the plasma concentration data. Tolerability was evaluated by adverse events (AEs) and laboratory examinations. Results: The range of time to maximum concentration (T(max)) was 1.5-6.0 h, with a linear increase in the exposure of CK over the dose range of 100-400 mg. Steady state was reached after the 7th administration, and the accumulation index range was 2.60-2.78. Sex differences were characterized by a higher exposure in females than males with the single administration after breakfast. In addition, no severe AEs were observed. Conclusion: CK was safe and well-tolerated over the treatment period. The sex- and food-related impacts on CK pharmacokinetics need further investigations to be validated. (Registration number: ChiCTR-TRC-14004824 and ChiCTR-IPR-15006107, http://www.chictr.org.cn/index.aspx).
29225245 Oral Methotrexate-related Lymphoproliferative Disease Presenting with Severe Osteonecrosis 2018 Feb 15 Long-term methotrexate (MTX) treatment can cause MTX-related lymphoproliferative disorder (MTX-LPD). We experienced a case of MTX-LPD that was associated with severe osteonecrosis of the jaw mimicking medication-related osteonecrosis of the jaw. The patient was an 81-year-old woman with rheumatoid arthritis (RA) who was treated with MTX and bisphosphonate. After 7 years, she was referred to our department for the assessment of giant ulcer and exposure of the alveolar bone of the left maxilla. Histopathological and immunological analyses confirmed a diagnosis of MTX-LPD. At seven months after the cessation of MTX treatment, the ulcerative and necrotic lesions had markedly decreased in size. A 1-year follow-up examination showed no evidence of recurrence and good RA control.
27846748 Beneficial effects of natural eggshell membrane (NEM) on multiple indices of arthritis in 2017 Sep OBJECTIVES: This study was performed to evaluate the potential efficacy of natural eggshell membrane (NEM) in collagen-induced arthritic rats, a well-established rodent model of inflammation and rheumatoid arthritis. METHODS: Rats with developing type II collagen-induced arthritis (CIA) were treated once daily by oral gavage on study days -14 to 17 with vehicle or NEM (52 mg/kg body weight). Rats were euthanized on study day 17. Efficacy was assessed by daily ankle caliper measurements, ankle diameter expressed as area under the curve (AUC(d0-17)), and histopathologic evaluation of ankles and knees. Serum biomarkers of cartilage function and inflammation [collagen type II C-telopeptide (CTXII), cartilage oligomeric matrix protein (COMP), and alpha-2-macroglobulin (A2M)] were measured by ELISA. RESULTS: Treatment with NEM resulted in significant beneficial effects on the daily ankle diameter measurements and ankle diameter AUC. Ankle and knee histopathology scores were significantly reduced (36% and 43% reduction of summed individual histopathology scores for ankle and knee, respectively; p < 0.05) toward normal for rats given NEM compared to vehicle controls. The percent reduction of serum CTXII, COMP, and A2M in NEM-treated rats ranged from 30% to 72% (p < 0.05). CONCLUSIONS: NEM significantly improved multiple aspects of inflammatory arthritis including inflammation, pannus, cartilage damage, bone resorption, and periosteal bone formation. This study provides further support for the use of CTXII, COMP, and A2M as relevant biomarkers that were responsive to NEM.
28883442 Interdisciplinary, Comprehensive Oral and Ocular Evaluation of Patients with Primary Sjög 2017 Sep 7 A comprehensive evaluation of oral and ocular symptoms and findings in primary Sjögren's syndrome (pSS) patients may provide valuable information for management. Medical history was obtained from female pSS patients, and sex- and age-matched non-SS patients with sicca symptoms (non-SS sicca controls) as well as healthy subjects without sicca complaints (healthy controls). Oral (Summated Xerostomia Inventory, SXI) and ocular (McMonnies Dry Eye questionnaire, MDEIS, and Ocular Surface Disease Index, OSDI) subjective complaints were recorded. Objective findings including clinical oral dryness scores (CODS), unstimulated and stimulated saliva secretion rates (UWS/SWS), Schirmer I test, tear osmolarity, tear film break-up time (TFBUT), and ocular surface staining (OSS) were determined. The pSS and non-SS sicca controls were extensively troubled by subjective dryness, while the pSS group had higher CODS, significantly lower saliva and tear secretion, shorter TFBUT and higher OSS than both control groups. Furthermore, candida counts were significantly higher in the pSS patients. In the pSS group, subjective oral dryness significantly correlated with ocular dryness (MDEIS: r = 0.5, OSDI: r = 0.413) and SWS was significantly correlated with Schirmer I (r = 0.419). The findings imply that interdisciplinary subjective and objective evaluation of patients with xerostomia and xerophthalmia not only have implications for patient care, but also may guide clinicians in differentiating between pSS and non-SS sicca patients.
27886700 Sjögren Syndrome and Other Causes of Sicca in Older Adults. 2017 Feb Dry eye and dry mouth symptoms are each reported by up to 30% of persons more than 65 years of age, particularly in women. Medication side effects are the most common contributing factors. The evaluation of these symptoms requires measures of ocular and oral dryness. Sjögren syndrome is the prototypic disease associated with dryness of the eyes and mouth and predominantly affects women in their perimenopausal and postmenopausal years. In addition to topical treatment of the mucosal dryness, patients with Sjögren syndrome may require treatment with systemic immunomodulatory and immunosuppressive agents to manage a variety of extraglandular manifestations.
28405473 Patient-reported outcomes from a phase III study of baricitinib in patients with conventio 2017 OBJECTIVES: To evaluate the effect of baricitinib on patient-reported outcomes (PROs) in patients with active rheumatoid arthritis (RA) and an inadequate response or intolerance to conventional synthetic disease-modifying antirheumatic drugs. METHODS: In this phase III study, patients were randomised 1:1:1 to placebo (N=228), baricitinib 2 mg once daily (QD, N=229) or baricitinib 4 mg QD (N=227). PROs included the Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient's Global Assessment of Disease Activity (PtGA), patient's assessment of pain, measures from patient electronic daily diaries (duration and severity of morning joint stiffness (MJS), Worst Tiredness, Worst Joint Pain), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), SF-36, EuroQol 5-D index scores and visual analogue scales (VAS) and the Work Productivity and Activity Impairment Questionnaire-RA. The primary time point for the study was week 12. Treatment comparisons were assessed with logistic regression for categorical measures and analysis of covariance for continuous variables. RESULTS: Statistically significant improvements were observed for both baricitinib groups versus placebo in HAQ-DI, PtGA, pain, daily diary measures, EuroQoL index scores and SF-36 physical component score at week 12 and for those measures when assessed at week 24. Baricitinib 2 mg and baricitinib 4 mg were statistically significantly improved versus placebo for the EuroQoL VAS and FACIT-F, respectively, at week 24. CONCLUSIONS: Baricitinib 2 or 4 mg provided significant improvement versus placebo in PROs across different domains of RA, including physical function, MJS, fatigue, pain and quality of life. TRIAL REGISTRATION NUMBER: NCT01721057; Results.
28614216 Refractory adult-onset Still disease complicated by macrophage activation syndrome and acu 2017 Jun RATIONALE: Myocarditis is a rare but potentially fatal complication of Still's disease (about 7% of total cases). PATIENT CONCERNS: A 42-year-old woman was admitted to our ward with high-grade fever, rash and polyarthralgia, lasting since 4 weeks and rapidly complicated by MAS and acute heart failure. DIAGNOSES: Adult Onset Still's Disease rapidly developping macrophage activation syndrome and disseminated intravascular coagulopathy, further complicated by iperacute myocarditis with cardiac arrest. INTERVENTIONS: After failure of conventional therapies (steroids plus cyclosporine and then biological therapy with Anakinra 100 mg/day), the patient was treated with anakinra 100 mg sc 1 fl 4 times a day. OUTCOMES: Fast clinical and laboratoristic improvement and subsequent disease remission with complete recovery of cardiac function. LESSONS: This is the first case report in which high doses of Anakinra have been used to treat a refractory AOSD complicated by MAS and myocarditis. In AOSD complicated by life-threatening conditions, probably we need to consider aggressive therapeutic approaches with higher doses of Il-1 receptor blocker to switch off the hyper-inflammation.
28451698 [Still's disease in children and adults]. 2017 Jun Systemic juvenile idiopathic arthritis (sJIA) is characterized by fever, arthritis, and other signs of systemic inflammation. Historically, sJIA was named Still's disease after George Frederic Still, who first reported patients. Individuals who manifest after the 16(th) birthday are diagnosed with adult onset Still's disease (AOSD). The pathophysiology of sJIA and AOSD are incompletely understood. Increased activation of inflammasomes and the expression of proinflammatory cytokines play a central role. S100 proteins, which can activate Toll-like receptors, thus, maintaining positive feedback loops, have also been detected at increased levels in sera from sJIA patients. Reduced expression of the immune-modulatory cytokine IL-10 may further contribute to immune cell activation and the production of proinflammatory molecules. Here, we discuss the clinical picture, differential diagnoses, the current pathophysiological understanding, and treatment options in sJIA and AOSD.
28963698 Hereditary lysozyme amyloidosis with sicca syndrome, digestive, arterial, and tracheobronc 2017 Nov Lysozyme amyloidosis (ALys) is a rare autosomal dominant hereditary systemic amyloidosis associated with a large spectrum of clinical manifestations. ALys phenotype mainly involves the digestive tract, liver and spleen, kidneys, lymph nodes, skin, and lachrymal and salivary glands. Very recently, cardiac involvement and peripheral neuropathy associated with a new p.Leu102Ser variant of lysozyme have been documented. In the present observation, we extend the phenotypic heterogeneity of ALys to the tracheobronchial tree with histologically proven bronchial ALys-amyloid deposits. We report the case of a 62-year-old man of Italian origin (Piedmont) diagnosed with ALys associated with the p.Trp82Arg variant. The patient complained of upper digestive symptoms, sicca syndrome, and lately recurrent pulmonary infections. Thoracic endoscopy revealed a fragile, inflammatory, and granulomatous aspect of the bronchi. Amyloid deposits were observed in the upper digestive tract, salivary glands, temporal artery, and tracheobronchial tree. Symptomatic treatment was offered. Recurrent pulmonary infections occurred during the follow-up. Lung involvement in hereditary ALys has only been exceptionally described. Although vascular involvement has already been reported in ALys in many organs, it never concerned cranial arteries. This case highlights the systemic nature of the amyloid protein variant deposits and expands the spectrum of clinical manifestations to chest involvement. The literature review highlights that hereditary ALys with the p.Trp82Arg variant is frequent in patients coming from Piedmont (Italy). Due to diffuse organs involvement related to ALys, it is important not to misdiagnose ALys for AL amyloidosis, the most frequent form of amyloidosis.
29375580 Increased Frequency of Peripheral B and T Cells Expressing Granulocyte Monocyte Colony-Sti 2017 OBJECTIVES: Granulocyte monocyte colony-stimulating factor (GM-CSF) is currently considered a crucial inflammatory mediator and a novel therapeutic target in rheumatoid arthritis (RA), despite the fact that its precise cellular sources remain uncertain. We studied the expression of GM-CSF in peripheral lymphocytes from RA patients and its change with antirheumatic therapies. METHODS: Intracellular GM-CSF expression was assessed by flow cytometry in stimulated peripheral B (CD19+) and T (CD3+) cells from RA patients (n = 40), disease (n = 31 including osteoarthritis n = 15, psoriatic arthritis n = 10, and systemic rheumatic diseases n = 6) and healthy (n = 16) controls. The phenotype of GM-CSF+ B cells was assessed as well as longitudinal changes in GM-CSF+ lymphocytes during methotrexate (MTX, n = 10) or anti-tumor necrosis factor (anti-TNF, n = 10) therapy. RESULTS: Among untreated RA patients with active disease (Disease Activity Score 28-C-reactive protein = 5.6 ± 0.89) an expanded population of peripheral GM-CSF+ B (4.1 ± 2.2%) and T (3.4 ± 1.6%) cells was detected compared with both disease (1.7 ± 0.9%, p < 0.0001 and 1.7 ± 1.3%, p < 0.0001, respectively) and healthy (0.3 ± 0.2%, p < 0.0001 and 0.6 ± 0.6%, p < 0.0001) controls. RA GM-CSF+ B cells displayed more commonly a plasmablast or transitional phenotype (37.12 ± 18.34% vs. 14.26 ± 9.46%, p = 0.001 and 30.49 ± 15.04% vs. 2.45 ± 1.84%, p < 0.0001, respectively) and less a memory phenotype (21.46 ± 20.71% vs. 66.99 ± 16.63%, p < 0.0001) compared to GM-CSF- cells. GM-CSF expression in RA patients did not correlate to disease duration, activity or serological status. Anti-TNF treatment led to a statistically significant decrease in GM-CSF+ B and T cells while MTX had no significant effect. DISCUSSION: This is the first study showing an expanded population of GM-CSF+ B and T lymphocytes in patients with active RA which declined after anti-TNF therapy.
28760536 Validation of the Fautrel classification criteria for adult-onset Still's disease. 2018 Feb OBJECTIVES: To validate the Fautrel classification criteria for adult-onset Still's disease (AOSD) and to compare the discriminative performance to that of the Yamaguchi criteria. METHODS: We retrospectively reviewed the medical charts of 426 patients who had serum ferritin level and percentage glycosylated ferritin assayed at the biochemistry laboratory of Bichat Hospital. Medical data were extracted by use of a standardized form. All clinical, biological, and imaging features were collected, as well, evidence favoring an alternative diagnosis, specifically symptoms suggestive of other immune-mediated inflammatory diseases (IMID) or active infections. Patients were classified as AOSD patients or controls according to a predefined procedure, including consultation with a multidisciplinary expert group. Algorithms corresponding to the Fautrel and Yamaguchi classification criteria were applied for each patient. RESULTS: In all, 54 AOSD and 278 control patients were included. For the Fautrel criteria, the sensitivity was 87.0%, specificity 97.8%, and positive and negative predictive values 88.7% and 97.5%, respectively. For the standard Yamaguchi set-without strict application of exclusion criteria-the sensitivity was 96.3%, specificity 98.9%, and positive and negative predictive values 94.5% and 99.3%, respectively. If we applied a stricter definition of exclusion criteria, the sensitivity of the Yamaguchi set decreased to 31.5%. As wall, 37 AOSD diagnoses were missed. CONCLUSION: This study validates the Fautrel classification criteria with a cohort independent of that used for the original publication. This criteria set demonstrates good sensitivity and specificity, overcomes exclusion criteria, and includes glycosylated ferritin level. It also confirms the high discriminative power of the Yamaguchi criteria, albeit substantially affected by how exclusion criteria are interpreted.
27775242 Corneal confocal microscopy alterations in Sjögren's syndrome dry eye. 2017 Aug PURPOSE: To evaluate light backscattering (LB) in corneal layers in patients with primary Sjögren's syndrome dry eye (SSDE) utilizing in vivo corneal confocal microscopy (IVCM) and to determine the eventual association with the lacrimal functional test values. METHODS: A complete ophthalmic evaluation, Schirmer test with and without stimulation, break-up time (BUT) and IVCM were performed on 55 patients affected by SSDE and in an age- and sex-matched cohort of healthy participants (HP). Light backscattering, measures as light reflectivity unit (LRU), detected by IVCM at Bowman's membrane (BM) at 50 μm, at 100 μm and at 200 μm deeper than BM was compared in the two groups. The correlations between LB values and lacrimal function results were evaluated. RESULTS: In patients affected by SSDE, LB was significantly higher (p < 0.001) in each corneal layer examined (+14 ± 6.33 LRU at BM), compared with HP. A good reverse correlation between the light reflectivity measures at BM with Schirmer test with (r = -0.91) and without (r = -0.90) stimulation and BUT (r = -0.88) was found. Correlations were lower in the deeper corneal layers. CONCLUSION: Even if our results should be confirmed in further studies with a larger population, these findings show that IVCM is a device able to detect alterations in corneal layers in SSDE patients related to the lacrimal function. Light backscattering (LB) could be very useful for clinical diagnosis and management of SSDE.
29390286 Purulent constrictive pericarditis caused by Salmonella enteritidis in a patient with adul 2017 Dec RATIONALE: Purulent pericarditis is a rare and usually fatal disease. Immunodeficiency state and preexisting pericardial effusion can predispose patients to infections. However, we are not aware of similar cases in patients with adult-onset Still's disease (AOSD). In addition, it is seldom caused by Salmonella bacteria. PATIENT CONCERNS: We report a 30-year-old woman with dyspnea on exertion and epigastric fullness. She was newly diagnosed with AOSD 4 months previously and medicated with prednisolone. DIAGNOSES: Transthoracic echocardiography (TTE) and computed tomography revealed a thickened pericardium with loculations in the pericardial space, consistent with purulent constrictive pericarditis. Subsequent cultures of blood and pericardial fluid yielded S enteritidis. INTERVENTIONS: She underwent subtotal pericardiectomy through a limited median sternotomy, and antibiotic therapy (ceftriaxone) for 1 month. OUTCOMES: The New York Heart Association functional classification downgraded from class III to class I. There was no recurrence during the 1-year follow-up. LESSONS: This case presents an opportunity to highlight the importance of considering purulent pericarditis in patients previously diagnosed with AOSD. High clinical suspicion, early diagnosis, and prompt management can result in a better outcome in purulent pericarditis.
29052562 Clinical Profile and Significance of Mucocutaneous Lesions of Primary Sjögren's Syndrome: 2017 Oct 20 BACKGROUND: Mucocutaneous lesions are common features of primary Sjögren's syndrome (pSS), but only a few studies have focused on them. To demonstrate the profile of mucocutaneous lesions of pSS and further explore their potential clinical significance, we performed a cross-sectional study on 874 patients. METHODS: Demographic data, clinical manifestations, and laboratory results of 874 pSS patients were collected. Patients were divided into two groups according to the presence of mucocutaneous lesions. Differences in primary symptoms and systemic impairments between the two groups were analyzed. Results of laboratory tests were also compared after excluding those who had taken corticosteroid from both groups. One-year follow-up was done, and occurrences of various new complications were compared. RESULTS: Among the 874 pSS patients, 181 patients had mucocutaneous lesions, accounting for 20.7%. Multiple mucocutaneous manifestations were displayed, and the top four most common types of lesions were purpuric eruptions (39.8%), urticaria (23.8%), Raynaud's phenomenon (14.9%), and angular stomatitis (9.9%). Incidences of pulmonary interstitial fibrosis, pulmonary bullae, leukopenia, and anemia were significantly higher among patients with mucocutaneous lesions (P < 0.05). Increase in IgG and decrease in C4 among patients with mucocutaneous lesions displayed statistical significance after excluding patients from both groups who had taken corticosteroid (P < 0.05). After one-year follow-up, patients with mucocutaneous lesions presented a slightly higher incidence of new complications compared to those without. CONCLUSIONS: Mucocutaneous manifestations of pSS patients were common and diverse. Patients with mucocutaneous manifestations had more systemic damages, higher level of IgG, and lower level of serum C4, suggesting a higher activity of the primary disease.
28933131 The clinical spectrum of primary Sjögren's syndrome: beyond exocrine glands. 2017 Sep 21 Although primary Sjögren's syndrome (pSS) is a mild indolent chronic disease mainly characterized by mucosal dryness in the majority of cases, a consistent subgroup of patients display extra-glandular manifestations. Virtually any organs and systems can be affected, leading to a more serious disease prognosis. Therefore, the prompt identification of patients at higher risk of extra-glandular manifestations is necessary to start a thorough follow up and an aggressive treatment. The aim of this review article is to provide an overview of epidemiological, clinical and serological features of extra-glandular manifestations in pSS as well as current knowledge about putative biomarkers useful in clinical practice.
29018564 Achieving comprehensive disease control in patients with early and established rheumatoid 2017 OBJECTIVE: To evaluate the achievement of comprehensive disease control (CDC) following 1 year of treatment with adalimumab+methotrexate versus methotrexate alone and whether early achievement of remission (at week 24 or 26) is associated with CDC at week 52 in patients with either early or established rheumatoid arthritis (RA). METHODS: Post hoc analyses were conducted in three clinical studies assessing treatment with adalimumab+methotrexate: DE019 (NCT00195702) enrolled patients with established RA who were methotrexate inadequate responders; OPTIMA (NCT00420927) and PREMIER (NCT00195663) enrolled methotrexate-naive patients with early RA. In OPTIMA, patients not achieving stable low disease activity at weeks 22 and 26 in the placebo+methotrexate group could receive open-label adalimumab+methotrexate for 52 weeks (Rescue ADA arm). CDC was defined as the simultaneous achievement of clinical remission (DAS28(CRP)<2.6), normal function (HAQ-DI<0.5) and absence of radiographic progression (ΔmTSS≤0.5). RESULTS: Regardless of disease duration, significantly more patients receiving adalimumab+methotrexate achieved CDC compared with methotrexate alone. In the adalimumab+methotrexate group, a numerically greater proportion of patients with early RA (~25%) versus established RA (14%) achieved CDC at 1 year; achievement of CDC was notably greater among patients who met criteria for remission at week 24 or 26 (~50% of patients with early RA and 39% with established RA). CONCLUSION: Treatment with adalimumab+methotrexate increases the likelihood of achieving CDC in patients with either early or established RA. Clinical remission at week 24 or 26 is associated with achievement of CDC at week 52. TRIAL REGISTRATION NUMBER: DE019 (NCT00195702), OPTIMA (NCT00420927), PREMIER (NCT00195663); Post-results.
28373872 Type I Interferon Gene Response Is Increased in Early and Established Rheumatoid Arthritis 2017 BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory debilitating disease that affects the joints in the early and productive phases of an individual's life. Several cytokines have been linked to the disease pathogenesis and are known to contribute to the inflammatory state characteristic of RA. The participation of type I interferon (IFN) in the pathogenesis of the disease has been already described as well as the identity of the genes that are regulated by this molecule, which are collectively known as the type I IFN signature. These genes have several functions associated with apoptosis, transcriptional regulation, protein degradation, Th2 cell induction, B cell proliferation, etc. This article evaluated the expression of several genes of the IFN signature in different stages of disease and their correlation with the levels of anticitrullinated protein antibodies (ACPA) anticarbamylated protein (Anti-CarP) antibodies. METHODS: Samples from individuals with early and established RA, high-risk individuals (ACPA+ and ACPA-), and healthy controls were recruited at "Unidad de Artritis y Rheumatismo" (Rheumatism and Arthritis Unit) in Guadalajara Jalisco Mexico. Determinations of ACPA were made with Eurodiagnostica ACPA plus kit. Anti-CarP determinations were made according to previously described protocols. RNA was isolated, and purity and integrity were determined according to RNA integrity number >6. Gene expression analysis was made by RT-qPCR using specific primers for mRNAs of the type I IFN signature. Relative gene expression was calculated according to Livak and Schmitgen. RESULTS: Significant differences in gene expression were identified when comparing the different groups for MXA and MXB (P < 0.05), also when comparing established RA and ACPA- in both IFIT 1 and G15. An increased expression of ISG15 was identified (P < 0.05), and a clear tendency toward increase was identified for HERC5. EPSTRI1, IFI6, and IFI35 were found to be elevated in the chronic/established RA and early RA (P < 0.05). Significant correlations were identified for the IFN signature genes with the levels of ACPA and anti-CarP (P < 0.05). CONCLUSION: Our data confirm previous observations in the role of IFN signature and the pathogenesis of RA. Also, we provide evidence of an association between several genes of the IFN signature (that regulate Th2 cells and B cell proliferation) with the levels of anti-CarP antibodies and ACPA.
28123781 Association of erythrocyte methotrexate-polyglutamate levels with the efficacy and hepatot 2017 OBJECTIVE: To assess the utility of erythrocyte methotrexate-polyglutamate (MTX-PG) concentrations in determining the safety and efficacy of MTX in patients with rheumatoid arthritis (RA). METHODS: 79 MTX-naïve patients with RA were enrolled in this prospective 76-week cohort study. MTX was initiated, and a predefined dose-escalation protocol was followed. Erythrocyte MTX-PG concentrations were measured using liquid chromatography. The associations of MTX-PG concentrations with disease activity and adverse events were analysed. RESULTS: Dose escalation of MTX resulted in increased MTX-PG concentrations and a decrease in the mean Disease Activity Score in 28 joints (DAS28). A significant association was observed between total MTX-PG concentrations and ΔDAS28 at week 12 (β=-0.013, p=0.003) and at week 24 (β=-0.014, p=0.003). The maximum MTX-PG levels were significantly higher in patients presenting with elevated transaminases (≥100 IU/L) than in those without (146 vs 106 nmol/L, p=0.009). Receiver operating characteristic curve analysis revealed that a total MTX-PG concentrations of 83 nmol/L at week 12 was the threshold for a DAS28 improvement of ≥1.2 at week 24, and 105 nmol/L was the threshold for transaminases of ≥50 IU/L and 131 nmol/L for transaminases of ≥100 IU/L. MTX-PG concentrations were strongly influenced by body mass index and a serum albumin level. CONCLUSIONS: MTX-PG concentrations are a useful biomarker in MTX therapy, in terms of efficacy and safety.
28814904 The journey of rheumatoid arthritis patients: a review of reported lag times from the onse 2017 BACKGROUND: Even after achieving tremendous advances in diagnosis and treatment of rheumatoid arthritis (RA), many of the patients undergo delays in diagnosis and initiation of treatment, which leads to worsening of the condition and poor prognosis. OBJECTIVE: The objective of this study was to perform a literature review to quantify the lag times in diagnosis and treatment of RA and study the reported factors associated with it. METHODS: The authors searched literature published until September 2016 in electronic full-text and abstract databases and hand-searched the suitable articles. RESULTS: The weighted average of median lag time from symptom onset to therapy was 11.79 months (12 studies, 5,512 patients, range 3.6-24.0 months). Lag1 was 3.14 months (onset of symptoms to first physician consultant; 12 studies, 6,055 patients, range 0-5.7 months); lag2 was 2.13 months (physician visit to RA specialist referral; 13 studies, 34,767 patients, range 0.5-6.6 months); lag3 was 2.91 months (consultation with rheumatologist to diagnosis; 3 studies, 563 patients, range 0-5 months), lag4 was 2.14 months (diagnosis to initiation of disease-modifying antirheumatic drug therapy; 5 studies, 30,685 patients, range 0-2.2 months). Numerous patient-and physician-related factors like gender, ethnicity, primary care physician knowledge of the condition, availability of diagnostics, and so on were responsible for the delays. CONCLUSION: This review estimated the delay times and identified the main factors for delay in RA patients in diagnosis and initiation of treatment. A most plausible solution to this is coordinated effort by the rheumatology and primary care physicians.