11. Somatic mutations and the risk of undifferentiated autoinflammatory disease in MDS : an under-recognized but prognostically important complicationAbdulla Watad, Mark Kačar, Nicola Luigi Bragazzi, Qiao Zhou, Miriam Jassam, Jan Taylor, Eve Roman, Alexandra Smith, Richard A. Jones, Howard Amital, 2021, izvirni znanstveni članek Povzetek: Objectives: We theorized that myelodysplastic syndrome (MDS) with somatic mutations and karyotype abnormalities are associated with autoinflammation, and that the presence of autoinflammatory disease affected prognosis in MDS. Methods: One hundred thirty-four MDS patients were assessed for the prevalence of autoinflammatory complications and its link with karyotypes and somaticmutation status. Autoinflammatory complications were described either as well-defined autoinflammatory diseases (AD) or undifferentiated "autoinflammatory disease" (UAD) (defined as CRP over 10.0 mg/L on five consecutive occasions, taken at separate times and not explained by infection). Several patient characteristics including demographic, clinical, laboratory, cytogenetics charts, and outcomes, were compared between different groups. Results: Sixty-two (46.3%) patients had an autoinflammatory complication manifesting as arthralgia (43.5% vs. 23.6%, p = 0.0146), arthritis (30.6% vs. 15.3%, p = 0.0340), skin rash (27.4% vs. 12.5%, p = 0.0301), pleuritis (14.5% vs. 4.2%, p = 0.0371) and unexplained fever (27.4% vs. 0%, p < 0.0001). AD were found in 7.4% of MDS patients (with polymyalgia rheumatic being the most frequently one). Classical autoimmune diseases were found only in 4 MDS patients (3.0%). Transcription factor pathway mutations (RUNX1, BCOR, WTI, TP53) (OR 2.20 [95%CI 1.02-4.75], p = 0.0451) and abnormal karyotypes (OR 2.76 [95%CI 1.22-6.26], p = 0.0153) were associated with autoinflammatory complications. Acute leukaemic transformation was more frequent in MDS patients with autoinflammatory features than those without (27.4% vs. 9.7%, p = 0.0080). Conclusions: Autoinflammatory complications are common inMDS. Somatic mutations of transcription factor pathways and abnormal karyotypes are associated with greater risk of autoinflammatory complications, which are themselves linked to malignant transformation and a worse prognosis.
Ključne besede: myelodysplastic syndromes - genetics, autoinflammation, undifferentiated autoinflammatory disease, molecular characterization, somatic mutations
Objavljeno v DiRROS: 31.03.2021; Ogledov: 1207; Prenosov: 816
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12. Prognostic impact of PD-1 and PD-L1 expression in malignant pleural mesothelioma : an international multicenter studyLuka Brčić, Thomas Klikovits, Zsolt Megyesfalvi, Berta Mosleh, Katharina Sinn, Richard Hritcu, Viktoria Laszlo, Tanja Čufer, Aleš Rozman, Izidor Kern, Katja Mohorčič, 2021, izvirni znanstveni članek Povzetek: Background: Programmed cell death 1/programmed death ligand 1 (PD-1/PD-L1) immune-checkpoint blockade is a promising new therapeutic strategy in cancer. However, expression patterns and prognostic significance of PD-L1 and PD-1 are still controversial in human malignant pleural mesothelioma (MPM). Methods: Formalin-fixed paraffin-embedded (FFPE) tumor samples from 203 MPM patients receiving standard treatment without immunotherapy were collected from 5 European centers. PD-L1 and PD-1 expression of tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs) were measured by immunohistochemistry and correlated with clinical parameters and long-term outcome. Results: High (>10%) PD-L1 TC and PD-1 TILs expressions were found in 18 (8%) and 39 (24%) patients, respectively. PD-L1 was rarely expressed by TILs [>/=1%, n=13 (8%); >10%, n=1]. No significant associations were found between the PD-L1 or PD-1 expression of TCs or TILs and clinicopathological parameters such as stage or histological subtype. Notably, patients with high (>10%) TC-specific PD-L1 expression exhibited significantly worse median overall survival (OS) (6.3 vs. 15.1 months of those with low TC PD-L1 expression; HR: 2.51, P<0.001). In multivariate cox regression analysis adjusted for clinical parameters, high TC PD-L1 expression (>10%) proved to be an independent negative prognostic factor for OS (HR: 2.486, P=0.005). There was no significant correlation between PD-L1 or PD-1 expression of TILs and OS. Conclusions: In this multicenter cohort study, we demonstrate that high (>10%) PD-L1 expression of TCs independently predicts worse OS in MPM. Further studies are warranted to investigate the value of PD-L1/PD-1 expression as a marker for treatment response in MPM patients receiving immunotherapy.
Ključne besede: mesothelioma - anatomy and histology - analysis, 1malignant pleural mesothelioma, programmed death-ligand 1, programmed cell death 1, PD-L1
Objavljeno v DiRROS: 31.03.2021; Ogledov: 1288; Prenosov: 560
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13. Challenges and solutions in early detection, rapid response and communication about potential invasive alien species in forestsMaarten De Groot, Richard O'Hanlon, Erin Bullas-Appleton, György Csóka, Ágnes Csíszár, Massimo Faccoli, Eugenio Gervasini, Natalia Kirichenko, Márton Korda, Aleksander Marinšek, Nikki Robinson, Craig Shuttleworth, Jon Sweeney, Elena Tricarico, Laura Verbrugge, David Williams, Simon Zidar, Jana Kus Veenvliet, 2020, pregledni znanstveni članek Povzetek: Invasive alien species (IAS) are an important threat to forests. One of the best ways to manage potential IAS is through early detection and rapid response (EDRR) strategies. However, when dealing with IAS in forests, EU regulations are divided between phytosanitary regulations and IAS regulations. A version of EDRR for the former has been in place in the EU for more than 15 years while the latter is still in the process of being implemented. During 2019, a workshop was held to gather international experts on different plant health pests and IAS. The purpose of this workshop was to identify the opportunities and difficulties in applying the EDRR system in the EU phytosanitary and IAS legislation to four species for providing suggestions to improve the EDRR system. The model species are well known and come from different trophic levels. These species were the American pokeweed (Phytolacca americana), the grey squirrel (Sciurus carolinensis); and the plant health pests Geosmithia morbida and Emerald ash borer (Agrilus planipennis). We identified the similarities in the challenges of early detection, rapid response and communication of these species. For all species, difficulties in species identification, knowledge gaps on the pathways of spread, a lack of resources and uncertainty over which national government service was the competent authority were identified as the main challenges. Other challenges like public perception for the grey squirrel or methodological problems were species-specific. Regarding the rapid response: public perception, determination of the eradication area, sufficient scientific capacity and the lack of resources were common challenges for all species. Therefore, collaboration between institutes dealing with plant health pests and IAS can lead to better control of both groups of unwanted %organisms in forests.
Ključne besede: early warning system, plant health legislation, EU IAS legislation, alien species, Geosmithia morbida, Emerald ash borer, American pokeweed, Grey squirrel, rapid response system
Objavljeno v DiRROS: 11.12.2020; Ogledov: 1660; Prenosov: 624
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15. Bela knjigaKatalin Bödi, Christian Doczekal, Philipp Novakovits, Richard Zweiler, Gregor Božič, Lilijana Grnjak, Blaž Sunko, Rok Sunko, 2015, strokovna monografija Ključne besede: elektronske knjige
Objavljeno v DiRROS: 12.07.2017; Ogledov: 2852; Prenosov: 697
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16. Smernice za sonaravno vzgajanje in trajnostno gojenje avtohtonih hitrorastočih drevesnih vrst na projektnem območju kot obnovljivega vira za proizvodnjo energijeGregor Božič, Mitja Černela, Christian Doczekal, Mitja Ferlan, Andreja Ferreira, Melita Hrenko, Igor Köveš, Aleksander Marinšek, Matej Rupel, Mitja Skudnik, Rok Sunko, Richard Zweiler, Peter Železnik, Vlado Bratkovič, 2015, strokovna monografija Ključne besede: elektronske knjige
Objavljeno v DiRROS: 12.07.2017; Ogledov: 2868; Prenosov: 779
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17. White bookKatalin Bödi, Christian Doczekal, Philipp Novakovits, Richard Zweiler, Gregor Božič, Lilijana Grnjak, Blaž Sunko, Rok Sunko, 2015, strokovna monografija Ključne besede: elektronske knjige
Objavljeno v DiRROS: 12.07.2017; Ogledov: 2737; Prenosov: 654
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