Objectives To assess the effects of Rituximab (RTX) on skin and lung fibrosis in patients with systemic sclerosis (SSc) belonging to the European Scleroderma Trial and Research (EUSTAR) cohort and using a nested case-control design. Methods Inclusion criteria were fulfilment of American College of Rheumatology classification criteria for SSc, treatment with RTX and availability of follow-up data. RTX-treated patients were matched with control patients from the EUSTAR database not treated with RTX. Matching parameters for skin/lung fibrosis were the modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), follow-up duration, scleroderma subtype, disease duration and immunosuppressive co-treatment. The primary analysis was mRSS change from baseline to follow-up in the RTX group compared with the control group. Secondary analyses included change of FVC and safety measures. Results 63 patients treated with RTX were included in the analysis. The case-control analysis in patients with severe diffuse SSc showed that mRSS changes were larger in the RTX group versus matched controls (N=25; %24.0%5.2% vs %7.7%4.3%; p=0.03). Moreover, in RTX-treated patients, the mean mRSS was significantly reduced at follow-up compared with baseline (26.6%1.4 vs 20.3%1.8; p=0.0001). In addition, in patients with interstitial lung disease, RTX prevented significantly the further decline of FVC compared with matched controls (N=9; 0.4%4.4% vs %7.7%3.6%; p=0.02). Safety measures showed a good profile consistent with previous studies in autoimmune rheumatic diseases. Conclusions The comparison of RTX treated versus untreated matched-control SSc patients from the EUSTAR cohort demonstrated improvement of skin fibrosis and prevention of worsening lung fibrosis, supporting the therapeutic concept of B cell inhibition in SSc.
COBISS.SI-ID: 32114137
Titanium and titanium alloys are considered to be one of the most applicable materials in medical devices because of their suitable properties, most importantly high corrosion resistance and the specific combination of strength with biocompatibility. In order to improve the biocompatibility of titanium surfaces, the current report initially focuses on specifying the topography of titanium dioxide (TiO2) nanotubes (NTs) by electrochemical anodization. The zeta potential (zeta-potential) of NTs showed a negative value and confirmed the agreement between the measured and theoretically predicted dependence of zeta-potential on salt concentration, whereby the absolute value of zeta-potential diminished with increasing salt concentrations. We investigated binding of various plasma proteins with different sizes and charges using the bicinchoninic acid assay and immunofluorescence microscopy. Results showed effective and comparatively higher protein binding to NTs with 100 nm diameters (compared to 50 or 15 nm). We also showed a dose-dependent effect of serum amyloid A protein binding to NTs. These results and theoretical calculations of total available surface area for binding of proteins indicate that the largest surface area (also considering the NT lengths) is available for 100 nm NTs, with decreasing surface area for 50 and 15 nm NTs. These current investigations will have an impact on increasing the binding ability of biomedical devices in the body leading to increased durability of biomedical devices.
COBISS.SI-ID: 28395303
Objective. To determine the prevalence and clinical association of anti-phosphatidylserine/prothrombin antibodies (aPS/PT) in patients with a history of pregnancy complications relevant to antiphospholipid syndrome (APS). Materials and Methods. Two hundred and eleven patients with a history of (a) three or more consecutive miscarriages before 10th week of gestation (WG) (n = 64), (b) death of a morphologically normal fetus beyond 10thWG (n = 72), (c) premature birth of a morphologically normal neonate before 34th WG due to eclampsia, preeclamsia and placental insufficiency (n = 33), and (d) less than three unexplained consecutive miscarriages before 10th WG (n = 42). Subjects sera were analyzed for lupus anticoagulant (LA), anti-cardiolipin (aCL), anti-beta2-glycoprotein I (anti-beta2GPI), and aPS/PT antibodies. Results. 41/169 (24.3%) of patients were positive for at least one measured aPL. The highest prevalence was found for aPS/PT and aCL (13.0% and 12.4%, resp.) followed by LA (7.7%) and anti-beta2GPI (7.1%). 11/169 with APS-related obstetric manifestations had only aPS/PT. 17.8% of patients were positive for LA or aCL and/or anti-beta2GPI; however when adding the aPS/PT results, an additional 7% of patients could be evaluated for APS. Conclusion. aPS/PT are associated with recurrent early or late abortions and with premature delivery irrespective of other aPL.
COBISS.SI-ID: 31904729
Inflammation in systemic sclerosis (SSc) is a prominent, but incompletely characterized fea- ture in early stages of the disease. The goal of these studies was to determine the circulat- ing levels, clinical correlates and biological effects of the acute phase protein serum amyloid A (SAA), a marker of inflammation, in patients with SSc. Circulating levels of SAA were determined by multiplex assays in serum from 129 SSc patients and 98 healthy con- trols. Correlations between SAA levels and clinical and laboratory features of disease were analyzed. The effects of SAA on human pulmonary fibroblasts were studied ex vivo. Elevat- ed levels of SAA were found in 25% of SSc patients, with the highest levels in those with early-stage disease and diffuse cutaneous involvement. Significant negative correlations of SAA were found with forced vital capacity and diffusion capacity for carbon monoxide. Pa- tients with elevated SAA had greater dyspnea and more frequent interstitial lung disease, and had worse scores on patient-reported outcome measures. Incubation with recombinant SAA induced dose-dependent stimulation of IL-6 and IL-8 in normal lung fibroblasts in cul- ture. Serum levels of the inflammatory marker SAA are elevated in patients with early dif- fuse cutaneous SSc, and correlate with pulmonary involvement. In lung fibroblasts, SAA acts as a direct stimulus for increased cytokine production. These findings suggest that sys- temic inflammation in SSc may be linked to lung involvement and SAA could serve as a po- tential biomarker for this complication.
COBISS.SI-ID: 31899609
This study aimed to investigate the retention of the second-line biologic disease-modifying antirheumatic drugs (bDMARDs) in rheumatoid arthritis patients failing their first tumor necrosis factor alpha inhibitor (TNFi). Data was extracted from the Slovenian registry (BioRx.si) on December 15, 2012. Baseline patient characteristics were compared between second-line TNFi and non-TNFi, and potential confounders were identified by the means of binary logistic regression. Differential drug retention was assessed using the Kaplan-Meier method and crude and inverse probability-weighted Cox proportional hazards regression models (Cox model). Two hundred thirty-eight out of 688 patients who received a TNFi as the first biologic were switched to another biologic: 130 to a second-line TNFi and 108 to either rituximab (31.5 %) or tocilizumab (68.5 %) (non-TNFi). Disease activity at starting second-line bDMARD and stopping the first-line TNFi due to either lack of effectiveness or loss of effectiveness were identified as potential confounders. There appears to be a statistically significant retention advantage of the non-TNFi over the second-line TNFi (log rank test, p%=%0.000). This advantage is retained even after taking into account the possible effect of confounders which was tested using the inverse probability-weighted Cox model [hazard ratio (HR) 4.39; 95 % confidence interval (CI) 2.62%8.01, p%(%0.001]. After the first-line TNFi's failure, a second-line TNFi is more likely to fail earlier than non-TNFi.
COBISS.SI-ID: 32177625