The perspective of Polish patients with rheumatoid arthritis - treatment expectations, patient-reported outcomes, and digital literacy (the SENSE study).

Introduction: A widely accepted treat-to-target strategy for rheumatoid arthritis (RA) requires the patient's perspective in making treatment decisions. However, data on treatment preferences and expectations of Polish patients with RA are scarce. The aim of the study was to determine the satisfaction with treatment and the nature of therapeutic preferences and expectations of Polish patients with moderate to severe RA. Material and methods: Fifty-two adult Polish patients with moderately to highly active RA were asked to complete patient-reported outcomes and patient-provided information questionnaires. Additionally, patient sociodemographic and clinical data and information on patient current and planned treatment strategies were collected. Results: The mean global assessment of patient satisfaction with treatment was 64.1 ±24.6, below the level of indicating satisfaction. Rheumatoid arthritis negatively impacted patients' lives, resulting in a 37.8% impairment of work efficiency and 45% impairment of total activity. Primary treatment expectations for patients were lasting relief of RA symptoms, reduced pain and swelling in joints, increased flexibility of joints, and general improvement of arthritis. The most acceptable potential side effect was weight gain and the least acceptable were increases in the risk of cardiovascular disease, infection, and malignancies. The rapid onset of the drug effect (up to 1 week) was a preference of 48.1% of patients. Access to internet health resources was important for 44.2% of patients, but the median total eHealth literacy score in the study population was 24.0 (interquartile range: 20.5-28.0, range 8-37), which means low digital health literacy (DHL). Conclusions: Understanding these treatment preferences and expectations of patients with RA is essential for clinical practitioners to facilitate shared treatment decision-making. Digital health literacy data suggest the need of further improvement.

The Profile of Serum Transferrin Isoforms in Rheumatoid Arthritis.

INTRODUCTION: Transferrin, a microheterogeneous iron-transporting N-glycoprotein, is an optimal model for the analysis of the glycosylation profile in rheumatoid arthritis (RA). The aim of this study was to assess the transferrin isoforms profile in RA patients at the time of diagnosis and then look into their associations with disease activity. METHODS: Serum samples were collected from 48 patients with RA. The patients were males (6) and females (42) (age range: 33-85 years). Control group consisted of 30 healthy volunteers. Transferrin isoforms were analysed by capillary electrophoresis on MINICAP electrophoretic system. RESULTS: There was a significant decrease in the relative concentrations of trisialo- (mean ± SD; 2.130 ± 1.112) and pentasialotransferrin (13.562 ± 3.088), and significant increase in tetrasialotransferrin (83.640 ± 3.165) in RA patients when compared to the control group (3.615 ± 1.156; 76.840 ± 5.621; 18.610 ± 6.027, respectively) (U Mann-Whitney test: p < 0.001 for all comparisons). There were no significant changes in the disialotransferrin concentrations in RA patients. Trisialotransferrin concentration correlated with RA activity expressed as DAS 28 in RA patients (p < 0.001). The low trisialotransferrin concentration was also associated with high platelet count and high ESR (p < 0.001 for both). Disialo-, tetrasialo- and pentasialotransferrin concentrations did not correlate with DAS 28. CONCLUSIONS: In patients with RA the serum profile of transferrin isoforms is altered. We predict that the levels of trisialylated isoforms of transferrin will serve as a useful biochemical marker of the RA activity.

Role of periostin in esophageal, gastric and colon cancer.

Periostin, also known as osteoblast-specific factor 2, is a cell-adhesion protein with pleiotropic properties. The protein serves a vital role in the maintenance and development of tooth and bone tissue, in addition to cardiac development and healing. Periostin levels are increased in several forms of cancer, including pancreatic, ovarian, colon, lung, breast, gastric, thyroid, and esophageal head and neck carcinomas. The present review highlights the key role of periostin in tumorigenesis, particularly in increasing cell survival, invasion, angiogenesis, epithelial-mesenchymal transition and metastasis of carcinoma cells by interacting with numerous cell-surface receptors, including integrins, in the phosphoinositide 3-kinase-Akt pathway. In addition, periostin actively affects the canonical Wnt signaling pathway of colorectal tumorigenesis. The current review focused on the involvement of periostin in the development of colorectal, esophageal and gastric cancer.

Changes of glycosylation of IgG in rheumatoid arthritis patients treated with methotrexate.

PURPOSE: In patients with active rheumatoid arthritis (RA) decrease of galactosylation is correlated with disease activity. The aim of our study was to evaluate an effect of methotrexate therapy on glycosylation disturbances of IgG in RA patients. MATERIALS/METHODS: IgG glycosylation in 40 patients with active RA treated with methotrexate for 12 months prior to and after treatment were compared. The control group consisted of 20 healthy volunteers. IgG glycosylation was assessed using biotinylated lectins and immunosorbent ELISA assay. For galactose specificity Datura stramonium lectin (DSA), for sialic acid Sambucus nigra (SNA) and Maackia amurensis (MAA) and for fucose residue Areulia auranta (AAA) lectins were used. RESULTS: In RA-cases N-glycan galactosylation and sialylation of IgG before treatment were significantly lower than in healthy subjects (for DSA, MAA lectins p<0.001 and SNA p<0.05). Significant increase of IgG galactosylation and sialylation in RA patients after therapy (for DSA, MAA and SNA lectin p<0.05) was detected. Moreover the glycosylation disturbances of N-glycan IgG were strongly associated with changes of disease activity based on disease activity score. For fucose residues significantly higher absorbency of AAA lectin in RA patients before treatment was observed compared to control subjects (p<0.05) and slightly, not significantly decreased after MTX therapy. CONCLUSIONS: Defect of galactosylation of IgG in RA patients is a useful marker of disease activity that may be used for the assessment of therapy effectiveness. The role of IgG fucosylation and sialylation in RA pathogenesis has still to be determined.

Regulation of serum matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 following rituximab therapy in patients with rheumatoid arthritis refractory to anti-tumor necrosis factor blockers.

In our article, we evaluated the regulatory effects of the infusions of rituximab, a monoclonal antibody directed against CD20(+) B cells, on the serum matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels in patients with active rheumatoid arthritis (RA) not responding to anti-tumor necrosis factor (anti-TNF) therapy. Twelve RA patients were planned to receive four infusions of 1,000 mg of rituximab at weeks 0, 2, 24 and 26. The therapy was combined with methotrexate (MTX) (20-30 mg/week). Seven patients were refractory to previously received infliximab, and five to etanercept. Serum concentrations of interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9) and TIMP-1 were measured by ELISA on weeks 0, 2, 12, 24, 36 and 52. Initial infusion of rituximab downregulated serum MMP-1 (p < 0.01), MMP-3 (p < 0.001), MMP-9 (p < 0.001) and TIMP-1 (p < 0.05) levels. Second drug administration caused even more remarkable reduction of measured MMPs (p < 0.001 in all cases) and TIMP-1 level (p < 0.01). These findings were accompanied by significantly decreased ratios of measured MMPs to TIMP-1. Next rituximab infusions on weeks 24 and 26 sustained the suppression of serum MMPs levels. Prior to the initial rituximab infusion, serum concentrations of studied MMPs and TIMP-1 significantly correlated with markers of RA activity such as disease activity score (DAS28) and CRP levels. Rituximab therapy, beside a rapid clinical improvement, reduced serum MMPs concentrations in RA patients refractory to anti-TNF treatment. Repeated infusions of rituximab maintained initial serum MMPs suppression.

[Pulmonary manifestations in rheumatoid arthritis]. / Manifestacje plucne w reumatoidalnym zapaleniu stawów.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by destructive cartilages, bones and other structures formed joints. RA belongs to connective tissue diseases represented by systemic nature, internal illness, extra-articular features and rapidly progress of atherosceirosis. The extra-articular complications cause the reduction of patient longevity. The frequency of symptoms in patient with RA and respiratory disorders occur in 10-20% of cases. Pulmonary complications are the second most common cause of premature of patient deaths. Respiratory disorders associated with RA are devided into 3 groups: infection, lung disease caused by drugs and pulmonary manifestation connected by RA. These last affect interstitial tissue, bronchioli, pulmonary vessels, pleura, also are presented by pulmonary rheumatoid nodules and pulmonary hypertension.

Serum chemokines in patients with rheumatoid arthritis treated with etanercept.

Chemokines promote leucocyte traffic into the synovium, leading to the initiation and progression of the rheumatoid arthritis (RA). The aim of the study was to determine the effects of etanercept, a soluble tumour necrosis factor receptor (sTNFr), on the serum chemokines levels in patients with active RA. Patients were treated with 50 mg of subcutaneous injection of etanercept per week and methotrexate (10-25 mg/week). Serum levels of interleukin-8 (IL-8), RANTES (regulated upon activation, normal T cell expressed and secreted) and monocyte chemoattractant protein-1 (MCP-1) were assessed by ELISA at months 0, 3, 6, 9 and 12, prior to injection. 3-month treatment with etanercept diminished serum concentrations of IL-8, RANTES and MCP-1 (P < 0.05, P < 0.01 and P < 0.001, respectively). Subsequent etanercept administrations prolonged decrease in serum chemokines levels and in the case of IL-8 even intensified the reduction of its concentration in serum. These changes were accompanied by significant decrease of disease activity score (DAS28) (in all cases P < 0.001). Prior to the first etanercept administration, serum concentrations of studied chemokines correlated with markers of RA activity such as the erythrocyte sedimentation rate (ESR) and DAS28. Following next drug injection such associations were less or not significant. Therapy with etanercept and MTX not only caused a clinical improvement but also diminished serum chemokines levels in RA patients. Further treatment with etanercept sustained chemokines suppression.

Coexistence of systemic sclerosis, scleroderma-like syndromes and neoplastic diseases.

Coexistence of rheumatic and neoplastic diseases may take different forms. Rheumatic paraneoplastic syndromes, including systemic sclerosis, scleroderma-like changes and Raynaud's phenomenon are induced by substances secreted by neoplastic cells and immunological disturbances connected are associated with malignancy. They may precede the clinical manifestation of neoplasm, occur simultaneously or after its diagnosis. In turn, chronic course of rheumatic diseases (Sjögren's syndrome, systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis) by immunologic stimulation may promote carcinogenesis. Genetic, environmental factors (viruses, chemical substances, radiation) and alterations of immunological surveillance may be the cause of both rheumatic and paraneoplastic disorders. Anticancer therapy may cause rheumatic diseases and immunosuppressive agents used in patients with rheumatic syndromes may have carcinogenic effect. Patients with long-standing or atypical course of rheumatic disorders, positive family or personal history of neoplastic disease, positive cancer markers, monoclonal antibodies or presence of other paraneoplastic syndromes should be diagnosed as possibly having occult neoplasm. In this paper we reviewed available literature on coexistence of rheumatic processes and malignancies to attract particular attention to practical aspects of this vital issue.

[Coexistence of scleroderma-like syndrome and idiopathic myelofibrosis in a 54-year-old female patient: case report]. / Wspólistnienie zespolu twardzinopodobnego i samoistnego wlóknienia szpiku u 54-letniej pacjentki: opis przypadku.

Systemic sclerosis (SSc) is characterized by immunological disturbances, vascular damage and overproduction of extracellular matrix by stimulated fibroblasts. It has been postulated that immunological reactions involved in the pathogenesis of SSc may promote the development of malignancies. Coexistence of this disease with neoplasmatic processes is relatively frequent. In our report we describe a case a 54-year-old woman with scleroderma-like syndrome, which has preceded the occurrence of idiopathic myelofibrosis by many years. Owing to multiple repeated diagnostic tests we managed to diagnose this disease at the early stage, which enabled effective therapy with remission of blood dyscrasia as well as inhibition of skin lesions and lung fibrosis.

[Secondary lethal catastrophic antiphospholipid syndrome in 24-years old female patient with overlap syndrome (systemic sclerosis and systemic lupus erythematosus)]. / Wtórny katastroficzny zespól antyfosfolipidowy zakonczony zgonem u 24-letniej pacjentki z zespolem nakladania twardziny ukladowej i tocznia rumieniowatego.

In our article we describe the case of 24 years old woman with overlap syndrome under form of systemic sclerosis and systemic lupus erythematosus complicated by secondary antiphospholipid syndrome (APS). The first manifestation of antiphospholipid syndrome was intrauterine fetal death. Afterwards pulmonary embolism occurred. After several weeks in result of catastrophic course of antiphospholipid syndrome coronary artery thrombosis and myocardial infarction occurred with following prominent left ventricle systolic failure and multi organ failure. The patient died about one month after discharge from the hospital.

[Quality of life of patients with ankylosing spondylitis]. / Jakosc zycia pacjentów z zesztywniajacym zapaleniem stawów kregoslupa.

Ankylosing spondylitis is ranked second among "great rheumatic diseases" which lead to considerable disability. The course of ankylosing spondylitis is chronic with variations in intensity of symptoms and is either continuously progressive or alternates with exacerbations and remissions. Difficulties in everyday life are due to limited motoric activity which makes full self-functioning rather impossible. The specificity of ankylosing spondylitis negatively affects the emotional state of patients. Patients are depressed, apathetic, discouraged to undertake treatment and rehabilitation. The aim of the present study was to assess the quality of life of patients with ankylosing spondylitis in four dimensions: physical, psychic, environmental and social; to determine the severity of anxiety and depression associated with the disease; and to analyze the quality of life and health. Diagnostic questionnaires were used in this study. Our study has shown that patients are unsatisfied with the quality of their health. In the course of the disease, physical and psychic symptoms exacerbate. Support and help are especially needed by persons living alone and by residents of villages. It seems that professional care, psychic support, education of the patient and of persons caring for him, and preparation to self-care are an integral part of therapy which may have an important effect in improving the quality of life.

[Defect of glycosylation of immunoglobulin G in rheumatoid arthritis patients]. / Zaburzenia glikozylacji immunoglobuliny G w przebiegu reumatoidalnego zapalenia stawów.

Rheumatoid arthritis (RA) is a multisystem disorder in which immunological abnormalities result in symmetrical joint inflammation, articular erosion, and extra-articular involvement. The etiology of RA is still unknown, but a defect in the glycosylation of IgG may be involved in its immunopathogenesis. Several studies have shown a correlation between the amount of IgG lacking galactose and the activity of RA. IgG galactosylation has been shown to be a useful marker of early RA and an indicator of poor prognosis. Analysis of IgG galactosylation may offer an insight into disease pathogenesis and may also be useful in RA diagnosis.

[Correlations between serum matrix metalloproteinase (MMP-1, MMP-3, MMP-9, MMP-13) concentrations and markers of disease activity in early rheumatoid arthritis]. / Korelacje pomiedzy stezeniem metaloproteinaz (MMP-1, MMP-3, MMP-9 i MMP-13) w surowicy krwi a wskaznikami aktywnosci choroby we wczesnym okresie reumatoidalnego zapalenia stawów.

The purpose of this study was to analyse the correlations between serum concentrations of the matrix metalloproteinases (MMP-1, MMP-3, MMP-9, MMP-13) and clinical markers of disease activity in patients with early rheumatoid arthritis (RA). The study group consisted of 30 RA patients, untreated with disease modifying antirheumatic drugs (DMARDs) or corticosteroids, with disease duration less than 3 years. The analysis of serum concentrations of MMPs was based on a quantitative sandwich ELISA. We observed the positive significant correlations between studied MMPs and clinical markers of disease activity, such as number of swollen joints or erythrocyte sedimentation rate (ESR). Furthermore, we revealed significant correlations between serum MMP-1, MMP-3, MMP-9, MMP-13 concentrations and disease activity score (DAS) (p < 0.01; p < 0.001; p < 0.001; p < 0.05 respectively). We conclude that studied matrix metallo-proteinases might be useful clinical markers of disease activity in early rheumatoid arthritis.

Reduction of soluble adhesion molecules (sICAM-1, sVCAM-1, and sE-selectin) and vascular endothelial growth factor levels in serum of rheumatoid arthritis patients following multiple intravenous infusions of infliximab.

INTRODUCTION: The purpose of this study was to determine the effect of repeated infusions of infliximab, a chimeric anti-tumor necrosis factor (anti-TNF)-alpha antibody, on the levels of soluble adhesion molecules and vascular endothelial growth factor (VEGF) in patients with active rheumatoid arthritis (RA). MATERIALS AND METHODS: The treatment design consisted of 9 infusions of infliximab (3 mg/kg) at weeks 0, 2, 6, and every 8 weeks thereafter. All patients had been receiving methotrexate (MTX; 7.5-20 mg/week). Serum levels of soluble intercellular adhesion molecule (sICAM)-1, vascular cell adhesion molecule (sVCAM)-1, E-selectin (sE-selectin), and VEGF were measured by ELISA at weeks 0, 2, 6, 14, and 38 prior to infusion, and at week 62. RESULTS: A remarkable decrease in serum sICAM-1 (p<0.001), sVCAM-1 (p<0.01), sE-selectin (p<0.01) and VEGF (p<0.001) levels was observed in RA patients after the initial dose of infliximab. The second administration of the drug was followed by an even more significant suppression of serum sICAM-1, sVCAM-1, sE-selectin, and VEGF (p<0.001 in all cases). Further infliximab infusions also significantly reduced serum soluble adhesion molecules and VEGF concentrations, although these were less effective. Infliximab treatment induced a significant decrease in the number of monocytes observed until the end of the study. CONCLUSIONS: Our study, besides a rapid suppression of disease activity, showed that serum soluble adhesion molecules and VEGF concentrations are down-regulated following anti-TNF-alpha antibody therapy combined with MTX. Repeated doses of infliximab sustained the reductions in the soluble adhesion molecules and VEGF concentrations, although they were less effective than the first and second infusions of infliximab.

Effect of repeated infliximab therapy on serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with rheumatoid arthritis.

OBJECTIVE: Matrix metalloproteinases (MMP) are involved in the articular tissue destruction processes in the pathogenesis of rheumatoid arthritis (RA). We investigated the effects of multiple infusions of infliximab, a chimeric anti-tumor necrosis factor-a (anti-TNF-a) antibody, on concentrations of serum MMP and tissue inhibitors of metalloproteinases (TIMP) in patients with active RA. METHODS: Patients with RA were scheduled to receive 9 infusions of infliximab (3 mg/kg) at Weeks 0, 2, 6, and every 8 weeks thereafter. The therapy was combined with methotrexate (MTX) (7.5-20 mg/week). Serum concentrations of interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9), TIMP-1, and TIMP-2 were measured by ELISA prior to infusion at Weeks 0, 2, 6, 14, 38, and 62. RESULTS: The initial infusion of infliximab downregulated serum levels of MMP-1 (p < 0.001), MMP-3 (p < 0.001), MMP-9 (p < 0.001), TIMP-1 (p < 0.01), and TIMP-2 (p < 0.05). The second drug administration caused even more remarkable reduction of measured MMP (p < 0.001 in all cases) but not of TIMP levels. These changes were accompanied by decreased ratios of measured MMP to TIMP. Further infliximab therapy also significantly suppressed serum MMP levels, but was less effective. Before the first infliximab infusion serum concentrations of MMP and TIMP correlated with markers of RA activity such as the Disease Activity Score and C-reactive protein levels. After further drug administrations such associations, although less significant, were also noted. CONCLUSION: Anti-TNF-a antibody therapy combined with MTX resulted in rapid clinical improvement and reduced serum MMP concentrations in patients with RA. Further infusions of infliximab maintained the decrease of MMP, although to a lesser extent than the first and second doses.

[Analysis of the acid glycoprotein heterogeneity in patients with arthritis]. / Analiza heterogennosci kwasnej glikoproteiny u chorych na zapalenie stawów.

The concentration measurement of the acute phase proteins in blood serum has been applied in differential diagnosis of inflammatory arthritis since a long time. However, it appeared that the qualitative changes such as the presence of different glycoforms of the acute phase protein that was a glycoprotein, enabled to differentiate acute inflammatory conditions including the chronic ones, and to determine the dynamics of inflammatory process. This phenomenon is defined as a main heterogeneity, whereas the determination of the proportions of particular glycoforms is known as glycosylation profile. The changes of this profile are well known in the course of acute inflammatory conditions such as: bacterial sepsis, skin burns complicated with bacterial infections or acute pancreatitis. Considerably less observations concern the chronic conditions as: rheumatoid arthritis, systemic lupus erythematosus and degenerative joint disease. The examination encompassed 25 patients with rheumatoid arthritis, 21 with systemic lupus erythematosus, 19 with reactive arthritis and 21 patients with degenerative joint disease whose diagnosis was established on the basis of international diagnostic criteria. In all these patient the changes of C-reactive protein (CRP), acid glycoprotein (AGP) as well as glycosylation profile of the AGP were evaluated. For this purpose the electrophoresis method of two affinity directions with concanavalin A was applied, whereas the concentration of particular acute phase protein was determined by Laurell's immunoelectrophoresis method. The variants of glycoprotein resulted from electrophoresis were calculated with aid of planimetric method, and the results were presented as a coefficient of glycosylation. The characteristic patterns of glycosylation profile in the course of systemic lupus erythematosus, rheumatoid arthritis and reactive arthritis may be useful in differential diagnosis of the above mentioned diseases.