Clinical characteristics of Polish patients with ANCA-associated vasculitides-retrospective analysis of POLVAS registry

Objective Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare small to medium-size vessel systemic diseases. As their clinical picture, organ involvement, and factors influencing outcome may differ between countries and geographical areas, we decided to describe a large cohort of Polish AAV patients coming from several referral centers-members of the Scientific Consortium of the Polish Vasculitis Registry (POLVAS). Methods We conducted a systematic multicenter retrospective study of adult patients diagnosed with AAV between Jan 1990 and Dec 2016 to analyze their clinical picture, organ involvement, and factors influencing outcome. Patients were enrolled to the study by nine centers (14 clinical wards) from seven Voivodeships populated by 22.3 mln inhabitants (58.2% of the Polish population). Results Participating centers included 625 AAV patients into the registry. Their distribution was as follows: 417 patients (66.7%) with GPA, 106 (17.0%) with MPA, and 102 (16.3%) with EGPA. Male-to-female ratios were almost 1:1 for GPA (210/207) and MPA (54/52), but EGPA was twice more frequent among women (34/68). Clinical manifestations and organ involvement were analyzed by clinical phenotype. Their clinical manifestations seem very similar to other European countries, but interestingly, men with GPA appeared to follow a more severe course than the women. Fifty five patients died. In GPA, two variables were significantly associated with death: permanent renal replacement therapy (PRRT) and respiratory involvement (univariate analysis). In multivariate analysis, PRRT (OR = 5.3; 95% confidence interval (CI) = 2.3–12.2), respiratory involvement (OR = 3.2; 95% CI = 1.06–9.7), and, in addition, age > 65 (OR = 2.6; 95% CI = 1.05–6.6) were independently associated with death. In MPA, also three variables were observed to be independent predictors of death: PRRT (OR = 5.7; 95% CI = 1.3–25.5), skin involvement (OR = 4.4; 95% CI = 1.02– 19.6), and age > 65 (OR = 6.3; 95% CI = 1.18–33.7). Conclusions In this first multicenter retrospective study of the Polish AAV patients, we have shown that their demographic characteristics, disease manifestations, and predictors of fatal outcome follow the same pattern as those from other European countries, with men possibly suffering from more severe course of the disease

Does administration of non-steroidal anti-inflammatory drug determine morphological changes in adrenal cortex: ultrastructural studies

Rofecoxib (Vioxx© made by Merck Sharp & Dohme, the USA) is a non-steroidal anti-inflammatory drug which belongs to the group of selective inhibitors of cyclooxygenasis-2, i.e., coxibs. Rofecoxib was first registered in the USA, in May 1999. Since then the drug was received by millions of patients. Drugs of this group were expected to exhibit increased therapeutic action. Additionally, there were expectations concerning possibilities of their application, at least as auxiliary drugs, in neoplastic therpy due to intensifying of apoptosis. In connection with the withdrawal of Vioxx© (rofecoxib) from pharmaceutical market, attempts were made to conduct electron-microscopic evaluation of cortical part of the adrenal gland in preparations obtained from animals under influence of the drug. Every morning animals from the experimental group (15 rats) received rofecoxib (suspension in physiological saline)—non-steroidal anti-inflammatory drug (Vioxx©, Merck Sharp and Dohme, the USA), through an intragastric tube in the dose of 1.25 mg during 8 weeks. In the evaluated material, there was found a greater number of secretory vacuoles and large, containing cholesterol and other lipids as well as generated glucocorticoids, lipid drops in cytoplasm containing prominent endoplasmic reticulum. There were also found cells with cytoplasm of smaller density—especially in apical and basal parts of cells. Mitochondria occasionally demonstrated features of delicate swelling. The observed changes, which occurred on cellular level with application of large doses of the drug, result from mobilization of adaptation mechanisms of the organism

TGFβ + small extracellular vesicles from head and neck squamous cell carcinoma cells reprogram macrophages towards a pro‐angiogenic phenotype

Transforming growth factor β (TGFβ) is a major component of tumor-derived small extracellular vesicles (TEX) in cancer patients. Mechanisms utilized by TGFβ+ TEX to promote tumor growth and pro-tumor activities in the tumor microenvironment (TME) are largely unknown. TEX produced by head and neck squamous cell carcinoma (HNSCC) cell lines carried TGFβ and angiogenesis-promoting proteins. TGFβ+ TEX stimulated macrophage chemotaxis without a notable M1/M2 phenotype shift and reprogrammed primary human macrophages to a pro-angiogenic phenotype characterized by the upregulation of pro-angiogenic factors and functions. In a murine basement membrane extract plug model, TGFβ+ TEX promoted macrophage infiltration and vascularization (p < 0.001), which was blocked by using the TGFβ ligand trap mRER (p < 0.001). TGFβ+ TEX injected into mice undergoing the 4-nitroquinoline-1-oxide (4-NQO)-driven oral carcinogenesis promoted tumor angiogenesis (p < 0.05), infiltration of M2-like macrophages in the TME (p < 0.05) and ultimately tumor progression (p < 0.05). Inhibition of TGFβ signaling in TEX with mRER ameliorated these pro-tumor activities. Silencing of TGFβ emerges as a critical step in suppressing pro-angiogenic functions of TEX in HNSCC

Charge-pumping characterization of FILOX vertical MOSFETs

This paper presents for the first time the results of charge-pumping (CP) measurements of FILOX vertical transistors. The aim of these measurements is to provide information on the density of interface traps at the Si-SiO2 interface fabricated in a non-standard process. Flat-band and threshold voltage, as well as density of interface traps are determined. Good agreement between threshold-voltage values obtained from CP and I-V measurements is observed

An Influence of Silicon Substrate Parameters on a Responsivity of MOSFET-Based Terahertz Detectors

Silicon n-channel MOS transistors are a promising solution for sub-terahertz radiation detection. Their sensitivity is strongly related to the device construction. A type and thickness of the device substrate are key parameters affecting the responsivity, because the silicon substrate is a medium for the radiation propagation and the radiation energy loss, which degrades the detection efficiency. This work is aimed at analysis of the silicon substrate characteristics effect on operation of the MOSFETs as the terahertz radiation sensors. A manufacturing of the MOSFETs on three different substrate types including changing the substrate thickness is described in the paper. Next, the fabricated devices were exposed to THz radiation and their photoresponses were measured. It may be concluded that MOSFETs on silicon-on-insulator wafers with locally thinned substrates demonstrate the highest photoresponse. However, the experiments with the MOSFETs on high resisivity wafers give also promising results

Applying shallow nitrogen implantation from rf plasma for dual gate oxide technology

The goal of this work was to study nitrogen implantation from plasma with the aim of applying it in dual gate oxide technology and to examine the influence of the rf power of plasma and that of oxidation type. The obtained structures were examined by means of ellipsometry, SIMS and electrical characterization methods

The influence of annealing (900?C) of ultra-thin PECVD silicon oxynitride layers

This work reports on changes in the properties of ultra-thin PECVD silicon oxynitride layers after high- temperature treatment. Possible changes in the structure, composition and electrophysical properties were investigated by means of spectroscopic ellipsometry, XPS, SIMS and electrical characterization methods (C-V, I-V and charge- pumping). The XPS measurements show that SiOxNy is the dominant phase in the ultra-thin layer and high-temperature annealing results in further increase of the oxynitride phase up to 70% of the whole layer. Despite comparable thickness, SIMS measurement indicates a densification of the annealed layer, because sputtering time is increased. It suggests complex changes of physical and chemical properties of the investigated layers taking place during high-temperature annealing. The C-V curves of annealed layers exhibit less frequency dispersion, their leakage and charge-pumping currents are lower when compared to those of as-deposited layers, proving improvement in the gate structure trapping properties due to the annealing process

EULAR/eumusc.net standards of care for rheumatoid arthritis : cross-sectional analyses of importance, level of implementation and care gaps experienced by patients and rheumatologists across 35 European countries

Objective As part of European League against Rheumatism (EULAR)/European Musculoskeletal Conditions Surveillance and Information Network, 20 user-focused standards of care (SoCs) for rheumatoid arthritis (RA) addressing 16 domains of care were developed. This study aimed to explore gaps in implementation of these SoCs across Europe. Methods Two cross-sectional surveys on the importance, level of and barriers (patients only) to implementation of each SoC (0-10, 10 highest) were designed to be conducted among patients and rheumatologists in 50 European countries. Care gaps were calculated as the difference between the actual and maximum possible score for implementation (ie, 10) multiplied by the care importance score, resulting in care gaps (0-100, maximal gap). Factors associated with the problematic care gaps (ie, gap≥30 and importance≥6 and implementation<6) and strong barriers (≥6) were further analysed in multilevel logistic regression models. Results Overall, 26 and 31 countries provided data from 1873 patients and 1131 rheumatologists, respectively. 19 out of 20 SoCs were problematic from the perspectives of more than 20% of patients, while this was true for only 10 SoCs for rheumatologists. Rheumatologists in countries with lower gross domestic product and non-European Union countries were more likely to report problematic gaps in 15 of 20 SoCs, while virtually no differences were observed among patients. Lack of relevance of some SoCs (71%) and limited time of professionals (66%) were the most frequent implementation barriers identified by patients. Conclusions Many problematic gaps were reported across several essential aspects of RA care. More efforts need to be devoted to implementation of EULAR SoCs