Usefulness of noninvasive diagnostic procedures for assessment of methotrexate hepatotoxicity in patients with rheumatoid arthritis.

Methotrexate (MTX) is recommended as a first-line treatment for rheumatoid arthritis (RA). There are no strict guidelines regarding monitoring for liver damage in RA patients. This study aimed to evaluate noninvasive diagnostic procedures in assessing liver fibrosis in RA patients. Ninety-six RA patients were recruited for this study. The procollagen III N-terminal peptide (PIIINP) serum level was measured in all patients. The Enhanced Liver Fibrosis score (ELF-1) was calculated for 82 patients. Transient elastography (TE) was performed in 91 patients, those examined were divided into two groups: a study and control group, comprising patients with and without risk factors for liver fibrosis, respectively. The TE result correlated only with the body mass index-BMI (p < 0.05); there was no correlation with the cumulative MTX dose (p = 0.33). The TE result was significantly higher in those with risk factors for liver fibrosis than in those without risk factors (TE result > = 7.1 kPa 28/42 vs 13/41, HR = 2.103, Mann-Whitney U test, approximately 0.02). There was a positive correlation between the PIIINP level and body weight (p = 0.028), cumulative MTX dose (p = 0.007), RA activity (p = 0.028) and diabetes mellitus (DM) (p = 0.001). There was a positive correlation between the ELF-1 score and age (p < 0.001), cumulative MTX dose (p = 0.007) and RA activity (p < 0.001). The PIIINP level and ELF-1 score are not organ specific, and readings may vary depending on RA activity. TE is organ specific and can be performed by a skilled ultrasonographer might be useful to assess actual liver condition.

Tofacitinib in the treatment of active rheumatoid arthritis - single-centre experience.

OBJECTIVES: To assess the efficacy and safety profile of tofacitinib taken orally at a dose of 10 mg/day in patients with severe active rheumatoid arthritis (RA). MATERIAL AND METHODS: The retrospective observational study included 10 patients (6 women and 4 men) with RA treated with tofacitinib. All the patients had high disease activity (DAS28 [ESR] > 5.1), despite therapy with two synthetic disease-modifying antirheumatic drugs (DMARDs). Before the initiation of treatment, routine laboratory tests were performed, and disease activity was assessed in all the subjects. RESULTS: The mean age of the patients in the study group was 58.18 years (43-67). The average duration of RA was 9.9 years (2-24). The mean baseline value of DAS28 (ESR) was 6.37. Tofacitinib was used in combination with a conventional DMARD in all study subjects: with methotrexate in the majority of patients, and with leflunomide and an antimalarial drug in three patients. The mean duration of therapy with tofacitinib was 7.57 months (3.9-10.8). A significant decrease in the disease activity was observed (p < 0.05). A reduction in DAS28 (ESR) score was seen already after the first month of therapy, and the trend was maintained during subsequent months of follow-up. The mean value of DAS28 (ESR) after 6 months was 2.78. A slight increase in the serum concentration of HDL cholesterol was observed during treatment. In one patient symptoms of chronic upper respiratory tract infection led to discontinuation of the drug. The observed adverse events were of mild/moderate degree. CONCLUSIONS: The results of our retrospective observational study conducted in the setting of daily clinical practice confirm a good clinical response to tofacitinib. Despite the observed adverse effects, in the light of the available data tofacitinib demonstrates a favourable safety profile. JAK kinase inhibitors - a new class of drugs - will enable a wider population of patients to achieve remission or low disease activity.

Magnetic Noise Prediction and Evaluation in Tunneling Magnetoresistance Sensors.

We propose a simple model for prediction of magnetic noise level in tunneling magnetoresistance (TMR) sensors. The model reproduces experimental magnetic 1/f and white noise components, which are dependent on sensors resistance and field sensitivity. The exact character of this dependence is determined by comparing the results with experimental data using a statistical cross-validation procedure. We show that the model is able to correctly predict magnetic noise level for systems within wide range of resistance, volume and sensitivity, and that it can be used as a robust method for noise evaluation in TMR sensors based on a small number of easily measurable parameters only.

Clinical and immunological characteristics of Polish patients with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with varied clinical manifestations, which creates difficulties and delays in establishing a diagnosis. OBJECTIVES: The aim of this study was to evaluate the prevalence and nature of the clinical symptoms of SLE, both at the onset of the disease and in its further course. An attempt to assess the immunological characteristics of the patients and to analyze autoantibodies variability over time was also made. MATERIAL AND METHODS: This retrospective study included 71 Caucasian patients, 63 women and 8 men, meeting the criteria for diagnosis of SLE according to ACR. RESULTS: The ratio of women to men was approximately 7.9:1. The average age of the onset of SLE was 31.5 years. The average time from the onset of symptoms to diagnosis was 5 years. The most common first manifestation of SLE were joint and muscles symptoms - 71.8%, skin lesions - 69.0%, fever - 57.7%. The main symptoms in the further course of the disease were neurological disorders - 69.0%, joint and muscle changes - 67.7%, and general symptoms - 59.2%. There was an increase in the incidence of renal involvement and neurological symptoms throughout the disease course. The most commonly detected antibodies were anti-dsDNA - 47.9%, anti-Ro/SSA - 40.8%, anti-nucleosomal antibodies - 29.6%, and lupus anticoagulant - 22.5%. A panel of antibodies typically did not change. CONCLUSIONS: There is no typical clinical picture of SLE, the population suffering from this disease is very various. Therefore, early and accurate diagnosis can be a big challenge for any clinician, which justifies the need for this type of study to better characterize the disease.

Understanding stability diagram of perpendicular magnetic tunnel junctions.

Perpendicular magnetic tunnel junctions (MTJ) with a bottom pinned reference layer and a composite free layer (FL) are investigated. Different thicknesses of the FL were tested to obtain an optimal balance between tunneling magnetoresistance (TMR) ratio and perpendicular magnetic anisotropy. After annealing at 400 °C, the TMR ratio for 1.5 nm thick CoFeB sublayer reached 180% at room temperature and 280% at 20 K with an MgO tunnel barrier thickness corresponding to the resistance area product RA = 10 Ohmµm2. The voltage vs. magnetic field stability diagrams measured in pillar-shaped MTJs with 130 nm diameter indicate the competition between spin transfer torque (STT), voltage controlled magnetic anisotropy (VCMA) and temperature effects in the switching process. An extended stability phase diagram model that takes into account all three effects and the effective damping measured independently using broadband ferromagnetic resonance technique enabled the determination of both STT and VCMA coefficients that are responsible for the FL magnetization switching.