In Vitro Inhibition of Xanthine Oxidase Purified from Arthritis Serum Patients by Nanocurcumin and Artemisinin Active Compounds.

Curcumin and artemisinin are commonly used in traditional East Asian medicine. In this study, we investigated the inhibitory effects of these active compounds on xanthine oxidase (XO) using allopurinol as a control. XO was purified from the serum of arthritis patients through ammonium sulfate precipitation (65%) and ion exchange chromatography on diethylaminoethyl (DEAE)-cellulose. The specific activity of the purified enzyme was 32.5 U/mg protein, resulting in a 7-fold purification with a yield of 66.8%. Molecular docking analysis revealed that curcumin had the strongest interaction energy with XO, with a binding energy of -9.28 kcal/mol. The amino acid residues Thr1077, Gln762, Phe914, Ala1078, Val1011, Glu1194, and Ala1079 were located closer to the binding site of curcumin than artemisinin, which had a binding energy of -7.2 kcal/mol. In vitro inhibition assays were performed using nanocurcumin and artemisinin at concentrations of 5, 10, 15, 20, and 25 µg/mL. Curcumin inhibited enzyme activity by 67-91%, while artemisinin had a lower inhibition ratio, which ranged from 40-70% compared to allopurinol as a control.

Dynamic platelet function: A novel biomarker in inflammatory arthritis?

BACKGROUND: Patients with inflammatory arthritis die prematurely of cardiovascular disease. Inflammation activates platelets. Since treatment of inflammatory arthritis is associated with reduced mortality, and decreased platelet reactivity reduces cardiovascular events, we hypothesised that platelet reactivity as measured by dynamic platelet function (DPF) would be increased in patients with inflammatory arthritis and that reactivity could be reduced with therapeutic intervention. OBJECTIVES: To characterise platelet function using a validated physiological assay in patients with inflammatory arthritis before and after disease improvement. METHODS: 22 patients were recruited and treated as per local protocol. DPF was measured at baseline and after clinical improvement. Video microscopy was utilised to measure dynamic platelet behaviour in microliters of blood perfused over von Willebrand factor (VWF) at arterial shear rates (1500 s-1). Motion-analysis software measured the number of platelets interacting with VWF, translocating across VWF, the speed and distance platelets travelled across VWF, and stably adhering to the surface. Platelet parameters at baseline and following improvement were compared using Wilcoxon signed rank test and paired student t-test. Changes in platelet function were correlated to inflammatory disease markers by Pearson Correlation. RESULTS: 18 patients completed the study. Platelet adhesion decreased and platelet motion increased following treatment. Tender joint count correlated with platelet adhesion (Pearson r = 0.616, p≤0.01) while CRP correlated with velocity of platelet movement (Pearson r = 0.563, p≤0.01). CONCLUSIONS: Improvement in clinical markers of inflammation is associated with a corresponding change in platelet function. Given the association between reduced mortality and decreased platelet reactivity our results suggest that an appropriate assay of platelet function could guide future therapy of patients with inflammatory arthritis.

Unravelling the Impact of the Genetic Variant rs1042058 within the TPL2 Risk Gene Locus on Molecular and Clinical Disease Course Patients with Inflammatory Bowel Disease.

Background: The single nucleotide polymorphism (SNP) rs1042058 within the gene locus encoding tumor progression locus 2 (TPL2) has been recently identified as a risk gene for inflammatory bowel disease (IBD). TPL2 has been shown to regulate pro-inflammatory signaling and cytokine secretion, while inhibition of TPL2 decreases intestinal inflammation in vivo. However, the clinical and molecular implications of this disease-associated TPL2 variation in IBD patients have not yet been studied. Methods: We analyzed the impact of the IBD-associated TPL2 variation using clinical data of 2145 genotyped patients from the Swiss IBD Cohort Study (SIBDCS). Furthermore, we assessed the molecular consequences of the TPL2 variation in ulcerative colitis (UC) and Crohn's disease (CD) patients by real-time PCR and multiplex ELISA of colon biopsies or serum, respectively. Results: We found that presence of the SNP rs1042058 within the TPL2 gene locus results in significantly higher numbers of CD patients suffering from peripheral arthritis. In contrast, UC patients carrying this variant feature a lower risk for intestinal surgery. On a molecular level, the presence of the rs1042058 (GG) IBD-risk polymorphism in TPL2 was associated with decreased mRNA levels of IL-10 in CD patients and decreased levels of IL-18 in the intestine of UC patients. Conclusions: Our data suggest that the presence of the IBD-associated TPL2 variation might indicate a more severe disease course in CD patients. These results reveal a potential therapeutic target and demonstrate the relevance of the IBD-associated TPL2 SNP as a predictive biomarker in IBD.

Significance of Interleukin (IL)-4 and IL-13 in Inflammatory Arthritis.

Interleukin (IL)-4 and IL-13 belong to the T helper 2 (Th2) cytokine family, along with IL-3, IL-5, and IL-9. These cytokines are key mediators of allergic inflammation. They have important immunomodulatory activities and exert influence on a wide variety of immune cells, such as B cells, eosinophils, basophils, monocytes, fibroblasts, endothelial cells, airway epithelial cells, smooth muscle cells, and keratinocytes. Recent studies have implicated IL-4 and IL-13 in the development of various autoimmune diseases. Additionally, these cytokines have emerged as potential players in pathogenesis of inflammatory arthritis. Recent findings suggest that the IL-4 and IL-13 might play a significant role in the downregulation of inflammatory processes underlying RA pathology, and beneficially modulate the course of the disease. This review summarizes the biological features of the IL-4 and IL-13 and provides current knowledge regarding the role of these cytokines in inflammatory arthritis.

Tofacitinib effectiveness in Blau syndrome: a case series of Chinese paediatric patients.

OBJECTIVE: Blau syndrome (BS), a rare, autosomal-dominant autoinflammatory syndrome, is characterized by a clinical triad of granulomatous recurrent uveitis, dermatitis, and symmetric arthritis and associated with mutations of the nucleotide-binding oligomerization domain containing 2 (NOD2) gene. Aim of this study was to assess the efficacy of tofacitinib in Chinese paediatric patients with BS. METHODS: Tofacitinib was regularly administered to three BS patients (Patient 1, Patient 2, and Patient 3) at different dosages: 1.7 mg/day (0.11 mg/kg), 2.5 mg/day (0.12 mg/kg), and 2.5 mg/day (0.33 mg/kg). The clinical manifestations of the patients, magnetic resonance imaging results, serological diagnoses, therapeutic measures and outcomes of treatments are described in this report. RESULTS: The clinical characteristics and serological diagnoses of all BS patients were greatly improved after the administration of tofacitinib treatment. All patients reached clinical remission of polyarthritis and improvements in the erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (CRP) and inflammatory cytokines. CONCLUSION: Tofacitinib, a Janus kinase (JAK) inhibitor, is a promising agent for BS patients who have unsatisfactory responses to corticosteroids, traditional disease-modifying antirheumatic drugs, and biological agents.

Effect of Ginseng Extracts on the Improvement of Osteopathic and Arthritis Symptoms in Women with Osteopenia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Ginsenosides are active compounds that are beneficial to bone metabolism and have anti-osteoporosis properties. However, very few clinical investigations have investigated the effect of ginseng extract (GE) on bone metabolism. This study aims to determine the effect of GE on improving bone metabolism and arthritis symptoms in postmenopausal women with osteopenia. A 12-week randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 90 subjects were randomly divided into a placebo group, GE 1 g group, and GE 3 g group for 12 weeks based on the random 1:1:1 assignment to these three groups. The primary outcome is represented by bone metabolism indices consisting of serum osteocalcin (OC), urine deoxypyridinoline (DPD), and DPD/OC measurements. Secondary outcomes were serum CTX, NTX, Ca, P, BsALP, P1NP, OC/CTX ratio, and WOMAC index. The GE 3 g group had a significantly increased serum OC concentration. Similarly, the GE 3 g group showed a significant decrease in the DPD/OC ratio, representing bone resorption and bone formation. Moreover, among all the groups, the GE 3 g group demonstrated appreciable improvements in the WOMAC index scores. In women with osteopenia, intake of 3 g of GE per day over 12 weeks notably improved the knee arthritis symptoms with improvements in the OC concentration and ratios of bone formation indices like DPD/OC.

Antiarthritic activity of OA-DHZ; a gastroprotective NF-κB/MAPK/COX inhibitor.

Arthritis, a primary autoimmune disorder having a global incidence of 2.03% person/year, is presently being treated by many commercially available drugs that treat symptomatically or improve the disease's clinical state; however, all the therapies pose varying amount of side effects. Therefore, it has become a fundamental need to search for therapeutics that offer better efficacy and safety profile, and the natural or nature-derived products are known for their outstanding performance in this arena. OA-DHZ, known to possess anti-inflammatory and analgesic properties, when explored for its efficacy against arthritis in adjuvant-induced arthritis (AIA) model, was found to inhibit paw edema by 34% and TNF-α, IL-6, and IL-1ß by 67%, 39%, and 45% respectively when compared to diseased control. It was also able to reduce the inflamed spleen size by 45% and successfully normalized biochemical and hematological changes that followed arthritis. In vitro studies revealed that the underlying mechanism for inhibiting arthritis progression might be due to NF-κB /MAPK pathway modulation. OA-DHZ also showed selective inhibition of COX-2 in vitro while showing gastroprotective effects when evaluated for ulcerogenic and antiulcer potential in vivo. In contrast to the results obtained from in vivo experimentation, there is a disparity in the pharmacokinetic profile of OA-DHZ, where it showed low oral exposure and high clearance rate. OA-DHZ being antiarthritic acting via NF-κB /MAPK/ COX inhibition while showing gastroprotective effects, can be a suitable candidate to be in the drug pipeline and further exploration.

Antirheumatic therapy is not associated with changes in circulating N-terminal pro-brain natriuretic peptide levels in patients with autoimmune arthritis.

BACKGROUND: Patients with autoimmune arthritis (AA) are at increased risk for impaired cardiac function and heart failure. This may be partly due to the effect of inflammation in heart function. The impact of antirheumatic drugs on cardiac dysfunction in AA remains controversial. Therefore, we aimed to examine effects of antirheumatic treatment on serum N-terminal pro-brain natriuretic peptide (NT-proBNP) in AA patients and its relationship to inflammatory markers. METHODS: We examined 115 patients with AA (64 rheumatoid arthritis (RA), 31 psoriatic arthritis and 20 ankylosis spondylitis) starting with methotrexate (MTX) monotherapy or tumor necrosis factor inhibitors (TNFi) with or without MTX co-medication. NT-proBNP (measured in serum by ECLIA from Roche Diagnostics), and other clinical and laboratory parameters were evaluated at baseline, after 6 weeks and 6 months of treatment. RESULTS: NT-proBNP levels did not change significantly after 6 weeks and 6 months of antirheumatic therapy (pbaseline-6weeks = 0.939; pbaseline-6months = 0.485), although there was a modest improvement from 6 weeks to 6 months in the MTX only treatment group (median difference = -18.2 [95% CI = -32.3 to -4.06], p = 0.013). There was no difference in the effects of MTX monotherapy and TNFi regimen on NT-proBNP levels. The changes in NT-proBNP after antirheumatic treatment positively correlated with changes in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Baseline NT-proBNP levels were related to baseline CRP and ESR levels, and some other established markers of disease activities in crude analyses. CONCLUSION: Circulating levels of NT-proBNP were related to established inflammatory markers at baseline, and the changes in NT-proBNP after antirheumatic treatment were positively related to these markers. Nevertheless, antirheumatic therapy did not seem to affect NT-proBNP levels compared to baseline, even though inflammatory markers significantly improved.

Association between arthritis treatments and ovarian reserve: a prospective study.

RESEARCH QUESTION: How do anti-Müllerian hormone (AMH) concentrations in women with and without arthritis compare? Is there an association between AMH and arthritis drug regimen? DESIGN: In this prospective cohort study, AMH was measured at two time points (T0 and T1) in 129 premenopausal women with arthritis. AMH at T0 was compared with that from a bank of serum samples from 198 premenopausal women without arthritis. Primary outcomes were: (i) diminished ovarian reserve (DOR) (AMH <1.1 ng/ml) and (ii) annual rate of AMH decrease. Univariate, multivariable and Firth logistic regression identified variables associated with annual AMH decrease in excess of the 75th percentile. RESULTS: Median time between T0 and T1 was 1.72 years. At time T0, median age-adjusted AMH in women with arthritis was significantly lower than that of women without arthritis (median 2.21 ng/ml versus 2.78 ng/ml; P = 0.009). Women with arthritis at highest risk for DOR had a history of tubal sterilization or were over the age of 35. Those with highest odds of having an annual AMH decrease in excess of the 75th percentile (over 28% decrease per year) were those: over the age of 35 or who sought care for infertility. Women with arthritis taking methotrexate alone (OR 0.08, 95% CI 0.01-0.67) or methotrexate plus tumour necrosis factor-alpha antagonists (OR 0.13, 95% CI 0.02-0.89) were less likely to be in the highest quartile of annual AMH decrease than women with arthritis not taking medication. CONCLUSIONS: Women with arthritis had lower AMH than healthy controls. Long-term methotrexate use was not associated with an annual AMH decrease.

Arthritis autoantibodies in individuals without rheumatoid arthritis: follow-up data from a Dutch population-based cohort (Lifelines).

OBJECTIVES: To assess whether the presence of arthritis autoantibodies alongside IgG ACPA predicts clinically suspect arthralgia in ACPA-positive subjects without RA. METHODS: In the population-based Lifelines cohort (n = 40 136), 308 IgG ACPA-positive individuals without RA were present. Serum levels of IgA ACPA, IgA and IgM RF, and IgG anti-carbamylated antibodies were measured at baseline. Individuals were divided based on the Connective tissue disease Screening Questionnaire after 2 years follow-up. Antibodies to Porphyromonas gingivalis were determined at baseline and related to presence of periodontitis and joint complaints at 2 years follow-up. RESULTS: Of 308 subjects 53.6% were also seropositive for IgA ACPA, 42.2% for IgM RF, 23.7% for IgA RF and 13.6% for anti-carbamylated antibodies. We defined 75 persons with clinically suspect arthralgia at risk for RA based on CTD Screening Questionnaire at follow-up. Significantly more seropositivity for IgM RF and higher levels of IgG ACPA, IgA ACPA and IgM RF were found in clinically suspect arthralgia compared with no-clinically suspect arthralgia. In multivariate logistic regression correcting for age, gender and never smoking, positivity for three or more extra autoantibodies was significantly associated with clinically suspect arthralgia. Although levels of anti-P. gingivalis were not different between groups, they were significantly correlated to levels of both RFs, and both ACPAs in clinically suspect arthralgia. CONCLUSIONS: ACPA-positive individuals without RA who develop clinically suspect arthralgia have more and higher levels of other arthritis autoantibodies at baseline. Levels of anti-P. gingivalis are not related to self-reported periodontitis or clinically suspect arthralgia, but are correlated to arthritis autoantibodies in clinically suspect arthralgia.

Coeliac disease is a risk factor for the development of seronegative arthritis in patients with autoimmune thyroid disease.

OBJECTIVE: Hashimoto's thyroiditis is known to cluster with other systemic autoimmune disorders. Rheumatic manifestations, such as a seronegative non-erosive polyarthritis have been described. The aim of this study was to evaluate the characteristics and the prevalence of rheumatic features in thyroiditis patients, and to ascertain whether the association with systemic autoimmune disorders improved the arthritis manifestations. METHODS: In total, 180 thyroiditis patients were enrolled. Major clinical and demographic characteristics have been recorded. Patients underwent a rheumatological clinical assessment and extra-articular manifestations allowing for a differential diagnosis with systemic autoimmune diseases and spondyloarthropathy. Presence of systemic autoimmune diseases was recorded. RESULTS: A total of 8.33% of thyroiditis patients shown a peripheral inflammatory arthritis (P = 0.002). Female gender (P = 0.042) and thyroid peroxidase (TPOAbs) positivity (P = 0.001) were more frequent. In total, 37 patients had systemic autoimmune diseases (P = 0.0003). A significant high prevalence of coeliac disease and Addison disease was found (P = 0.034 and P = 0.049, respectively). In patients with coeliac disease, the articular manifestations were more frequent (21.21%) (P = 0.001) and the risk to develop joint involvement was 2.96. CONCLUSION: Although we found an articular involvement in about one-third of thyroiditis patients, the prevalence of inflammatory arthropathy was only 8.33%. The prevalence of other coexisting autoimmune disorders was 34.26% with a significant prevalence of coeliac disease (7.41%). Thyroiditis patients with coeliac disease have an articular involvement more frequently than those without. In these patients, we have found a high risk of developing arthritis than patients with only thyroiditis, suggesting cumulative autoimmune effects in the developing articular involvement.

The Potential Effect of Aberrant Testosterone Levels on Common Diseases: A Mendelian Randomization Study.

Testosterone has historically been linked to sexual dysfunction; however, it has recently been shown to affect other physical and mental attributes. We attempted to determine whether changes in serum testosterone could play a role in chronic or degenerative diseases. We used two separate genetic instruments comprising of variants from JMJD1C and SHBG regions and conducted a two-sample Mendelian randomization for type II diabetes (T2D), gout, rheumatoid arthritis (RA), schizophrenia, bipolar disorder, Alzheimer's disease and depression. For the JMJD1C locus, one unit increase in log transformed testosterone was significantly associated with RA (OR = 1.69, p = 0.02), gout (OR = 0.469, p = 0.001) and T2D (OR = 0.769, p = 0.048). Similarly, one unit increase in log transformed testosterone using variants from the SHBG locus was associated with depression (OR = 1.02, p < 0.0001), RA (OR = 1.254, p < 0.0001) and T2D (OR = 0.88, p < 0.0001). Our results show that low levels of serum testosterone levels may cause gout and T2D, while higher than normal levels of testosterone may result in RA and depression. Our findings suggest that fluctuations in testosterone levels may have severe consequences that warrant further investigation.

Novel biomarkers of a peripheral blood interferon signature associated with drug-naïve early arthritis patients distinguish persistent from self-limiting disease course.

We profiled gene expression signatures to distinguish rheumatoid arthritis (RA) from non-inflammatory arthralgia (NIA), self-limiting arthritis (SLA), and undifferentiated arthritis (UA) as compared to healthy controls as novel potential biomarkers for therapeutic responsiveness. Global gene expression profiles of PBMCs from 43 drug-naïve patients presenting with joint symptoms were evaluated and differentially expressed genes identified by comparative analysis with 24 healthy volunteers. Patients were assessed at presentation with follow up at 6 and 12 months. Gene ontology and network pathway analysis were performed using DAVID Bioinformatics Resources v6.7. Gene expression profiles were also determined after disease-modifying anti-rheumatic drug (DMARD) treatment in the inflammatory arthritis groups (i.e. RA and UA) and confirmed by qRT-PCR. Receiver operating characteristic (ROC) curves analysis and Area Under the Curve (AUC) estimation were performed to assess the diagnostic value of candidate gene expression signatures. A type I interferon (IFN) gene signature distinguished DMARD-naïve patients who will subsequently develop persistent inflammatory arthritis (i.e. RA and UA) from those with NIA. In patients with RA, the IFN signature is characterised by up-regulation of SIGLEC1 (p = 0.00597) and MS4A4A (p = 0.00000904). We also identified, EPHB2 (p = 0.000542) and PDZK1IP1 (p = 0.0206) with RA-specific gene expression profiles and elevated expression of the ST6GALNAC1 (p = 0.0023) gene in UA. ROC and AUC risk score analysis suggested that MSA4A (AUC: 0.894, 0.644, 0.720), PDZK1IP1 (AUC: 0.785, 0.806, 0.977), and EPHB2 (AUC: 0.794, 0.723, 0.620) at 0, 6, and 12 months follow-up can accurately discriminate patients with RA from healthy controls and may have practical value for RA diagnosis. In patients with early inflammatory arthritis, ST6GALNAC1 is a potential biomarker for UA as compared with healthy controls whereas EPHB2, MS4A4A, and particularly PDZK1IP1 may discriminate RA patients. SIGLEC1 may also be a useful marker of disease activity in UA.

The Effects of Adalimumab in Behçet Disease Patients on Clinical Manifestations and on Pro-Inflammatory Cytokines Milieu: Long-Term Follow-Up.

BACKGROUND: Behçet's disease is a multi-systemic chronic relapsing inflammatory disease, classified among the vasculitides. The heterogeneity of clinical manifestations challenges the disease management. OBJECTIVES: To assess efficacy and safety of adalimumab in patients with active persistent Behçet's arthritis who did not respond to disease-modifying anti-rheumatic drugs and to assess the impact of treatment on the cytokine milieu. METHODS: Our cohort comprised 10 patients with active arthritis who received adalimumab in a 24-week investigator-initiated prospective open-label study. Patients who relapsed within 12 weeks following adalimumab discontinuation could enter a 3-year extension study. The patients underwent a comprehensive assessment including questionnaires and measurement of inflammatory cytokines, adalimumab serum levels, and anti-drug antibodies. RESULTS: A significant improvement was observed in arthritis, disease activity visual analogue scales, Behçet's disease current activity form, and interleukin-6 (IL-6) levels, but not in health assessment questionnaire and functional assessment of chronic illness therapy fatigue scale questionnaire. Resolution of oral and urogenital ulcers was achieved in all patients. Significant reduction of pain was reported by 40% of patients. The disease relapsed in 9 of 10 patients, within 2-6 weeks following adalimumab discontinuation. Of the 7 patients who continued the study, arthritis was resolved in 5. Two patients with high neutralizing antidrug antibodies titer relapsed. CONCLUSIONS: Adalimumab treatment achieved a significant improvement in arthritis, mucocutaneous manifestations, and IL-6 levels in all study patients but only 40% reported significant pain reduction. The arthritis relapsed in 90% of patients following adalimumab discontinuation and long-term treatment was required.

Association between daily level of objective physical activity and C-Reactive protein in a representative national sample of adults with self-reported diagnosed arthritis or fibromyalgia.

PURPOSE: Examine the association between physical activity and sedentary time with high sensitivity C-Reactive protein levels in adults with arthritis and fibromyalgia. We also investigated the dose of physical activity that was associated with lower clinical levels of high sensitivity C-Reactive protein (< 3 mg/L). MATERIALS AND METHODS: Observational design was used to evaluate the variables of interest-based on the Canadian Health Measures Survey cycle 1-3 (2007-2012). Generalized adjusted additive models were used to explore the shape of the association between high sensitivity C-Reactive protein, daily physical activity, step count and sedentary time. High sensitivity C-Reactive protein was measured with blood samples. Physical activity, number of steps and sedentary time were objectively assessed using an Actical accelerometer. RESULTS: Daily moderate to vigorous physical activity and step count were significantly associated with lower high sensitivity C-Reactive protein levels, but daily light physical activity and sedentary time were not associated with high sensitivity C-Reactive protein levels, even after controlling for age, sex, daily smoking, body mass index, household income, level of education levels, marital status, work year and accelerometer wear time and season of accelerometer. Non-linear dose-response patterns were observed between daily moderate to vigorous physical activity as well as step count with high sensitivity C-Reactive protein levels. Lower high sensitivity C-Reactive protein levels were associated with 1-150 min of daily moderate to vigorous physical activity and with daily step count starting at 4000 in people with arthritis. Adults with fibromyalgia had lower levels of high sensitivity C-Reactive protein when engaging in 10-35 min of daily moderate to vigorous physical activity and in 5000-9000 daily steps. Optimal and specific doses of daily moderate to vigorous physical activity and steps were independently related to lower high sensitivity C-Reactive protein levels in adults with arthritis and fibromyalgia. CONCLUSIONS: Daily moderate to vigorous physical activity and step count were associated with high sensitivity C-Reactive protein levels that were below the clinical threshold. Given the positive outcomes of physical activity on health, adults with arthritis and fibromyalgia may benefit from these specific recommendations.

Vitamin C and inflammatory cytokine levels in elective total knee arthroplasty.

BACKGROUND: Vitamin C levels are decreased in arthritis patients and reduced levels following surgery may impair adequate healing. AIM: This study measured changes in vitamin C and inflammatory markers in patients undergoing total knee arthroplasty (TKA). METHODS: Venous blood samples were collected from 10 patients during the preoperative to postoperative period. Vitamin C, interleukin-1ß, interleukin-6 (IL-6), and C-reactive protein (CRP) levels were measured using various assays. RESULTS: No significant changes in vitamin C levels were measured. However, all participants had suboptimal preoperative vitamin C levels and 90% had suboptimal levels postoperatively. IL-6 and CRP levels significantly increased during the immediate postoerative period. CONCLUSION: There was a rise in inflammation following TKA while vitamin C levels did not significantly change during this short study period. Of note, every patient had suboptimal vitamin C levels prior to surgery and 90% continued with suboptimal levels two days postoperatively.

Antibody response patterns in chikungunya febrile phase predict protection versus progression to chronic arthritis.

Chikungunya virus (CHIKV) infection causes acute febrile illness in humans, and some of these individuals develop a debilitating chronic arthritis that can persist for months to years for reasons that remain poorly understood. In this study from India, we characterized antibody response patterns in febrile chikungunya patients and further assessed the association of these initial febrile-phase antibody response patterns with protection versus progression to developing chronic arthritis. We found 5 distinct patterns of the antibody responses in the febrile phase: no CHIKV binding or neutralizing (NT) antibodies but PCR positive, IgM alone with no NT activity, IgM alone with NT activity, IgM and IgG without NT activity, and IgM and IgG with NT activity. A 20-month follow-up showed that appearance of NT activity regardless of antibody isotype or appearance of IgG regardless of NT activity during the initial febrile phase was associated with a robust protection against developing chronic arthritis in the future. These findings, while providing potentially novel insights on correlates of protective immunity against chikungunya-induced chronic arthritis, suggest that qualitative differences in the antibody response patterns that have evolved during the febrile phase can serve as biomarkers that allow prediction of protection or progression to chronic arthritis in the future.

Clinical utility of serum concentrations of adalimumab as predictor of treatment adherence. / Utilidad de las concentraciones séricas de adalimumab como predictores de adherencia al tratamiento.

OBJECTIVE: to evaluate the usefulness of serum concentrations (Sc) of adalimumab (ADA) as a predictor of medication adherence using the medication possession ratio (MPR) and Morisky Green test (MGT) in patients with chronic inflammatory diseases. MATERIAL AND METHOD: Design a prospective descriptive cohort study. INCLUSION CRITERIA: adult patients diagnosed with inflammatory arthropathy (IA) or inflammatory bowel disease (IBD) treated with ADA. EXCLUSION CRITERIA: positive anti-adalimumab antibody. VARIABLES: sex, age, diagnosis, dosage regimen, Sc (mg/mL), MPR (MPR ≥ 80% adherent) and MGT (non-adherent or adherent). Statistical analysis was performed using STATA v13.0. RESULTS: Forty-five patients (23 women) with an age of 52.22 (14.39) years, 17 IBD (37.78%), 26 IA (57.78%) and 2 with both conditions (4.44%) treated with 40mg ADA every 14 days (42/45; 93.33%) or every 7 days (3/45; 6.67%). We detected subtherapeutic Sc in 22.22% of patients (10/45); 10% (1/10) were classified as non-adherent and 90% (9/10) as adherent according to MGT and MPR. The quantification of Sc shows weak agreement with MPR, as was the case with the indirect methods of each (MPR and MGT). The association was slightly greater when the indirect methods were compared to each other (0.244 vs. 0.378). CONCLUSION: the determination of Sc of ADA alone has limited utility in the detection of non-adherent patients.

Síndrome RS3PE con factor reumatoide positivo / RS3PE syndrome with positive rheumatoid factor

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