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122. 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, original scientific article Abstract: 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.
Keywords: mesothelioma - anatomy and histology - analysis, 1malignant pleural mesothelioma, programmed death-ligand 1, programmed cell death 1, PD-L1
Published in DiRROS: 31.03.2021; Views: 1277; Downloads: 548
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123. Deset let Državnega presejalnega programa za raka dojk DoraKatja Jarm, Kristijana Hertl, Mateja Krajc, Cveto Šval, Veronika Kutnar, Mateja Kurir-Borovčić, Maja Primic-Žakelj, Vesna Zadnik, Maksimiljan Kadivec, 2020, original scientific article Abstract: Priporočila za vzpostavitev presejalnih programov za raka dojk je leta 2003 izdala Evropska komisija in države članice Evropske unije pozvala, da jih vzpostavijo do leta 2008. V Sloveniji od leta 2008 deluje Državni program za raka dojk DORA, ki je konec leta 2017 vključeval vse slovenske ženske iz
ciljne skupine. Ženske v starosti od 50 do 69 let so vsaki dve leti pisno vabljene na presejalni pregled z mamografijo, ki omogoča odkritje še netipnih sprememb v dojki. Ob sumljivih spremembah na mamografiji so povabljene na nadaljnjo obravnavo, če je odkrit rak dojke, pa tudi na zdravljenje. Od leta 2018 v okviru programa deluje 21 mamografov v 16 stacionarnih in 3 mobilnih presejalnih
enotah, kjer se opravljajo presejalne mamografije, in 2 presejalno- diagnostična centra za nadaljnjo obravnavo žensk in zdravljenje raka, odkritega v presejanju. Program DORA deluje v skladu z visokimi standardi Evropskih smernic za zagotavljanje kakovosti presejanja za raka dojk in zagotavlja enako obravnavo za vse udeleženke v katerikoli presejalni enoti v Sloveniji. Cilj presejalnega programa je ob vsaj 70-odstotni udeležbi žensk doseči znižanje umrljivosti za rakom dojk v ciljni populaciji za 25–30 %. Letno merjeni kazalniki kakovosti programa kažejo, da je program učinkovit in vodi k omenjenemu cilju. Značilnosti slovenskega organiziranega programa so: centraliziran populacijski program, vabljenje žensk z vnaprej določenim terminom slikanja, dvojno odčitavanje, konsenz konferenca, nadaljnja obravnava je del presejalnega postopka, multidisciplinarni sestanki, presejalni register z enotno aplikacijo za vnašanje vseh presejalnih korakov, od vabila do mamografij in nadaljnje obravnave, nadzor kakovosti dela radioloških inženirjev in radiologov, stalen strokovni nadzor nad izvajalci programa in letno merjenje kazalnikov kakovosti programa.
Keywords: presejalni programi, rak dojk, presejalni register
Published in DiRROS: 18.03.2021; Views: 1419; Downloads: 413
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124. Posodobljena priporočila diagnostike in zdravljenja diferenciranega raka ščitniceAlenka Grošel, Andraž Perhavec, Andrej Doma, Andreja A. Schwarzbartl-Pevec, Andreja Klevišar Ivančič, Andrej Vogrin, Barbara Vidergar-Kralj, Barbara Gazić, Barbara Perić, Blaž Krhin, Cvetka Grašič-Kuhar, Edvard Pirnat, Ivana Žagar, Jerca Blazina, Katica Bajuk-Studen, Katja Zaletel, Margareta Strojan Fležar, Marko Hočevar, Marko Kokalj, Marta Dremelj, Nebojša Glumac, Nikola Bešić, Olga Blatnik, Simona Gaberšček, Snežana Pavlović Djokić, Ulrika Klopčič, Veronika Kloboves-Prevodnik, Zorica Čekić, 2020, dictionary, encyclopaedia, lexicon, manual, atlas, map Keywords: rak ščitnice, diferencirani rak, zdravljenje, smernice
Published in DiRROS: 12.03.2021; Views: 1333; Downloads: 414
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125. Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategiesJean Bousquet, Jean-Paul Cristol, Wienczyslawa Czarlewski, Josep M. Antò i Boquè, Adrian Martineau, Tari Haahtela, Susana C. Fonseca, Guido Iaccarino, Hubert Blain, Alessandro Fiocchi, Nisera Bajrović, Natalija Edelbaher, Maja Jošt, Peter Kopač, Anja Koren, Mitja Košnik, Karmen Kramer Vrščaj, Samo Kreft, Nika Lalek, Bojan Madjar, Tonka Poplas-Susič, Irma Rozman Sinur, Tanja Soklič, Katja Triller Vadnal, Nadja Triller, Jure Urbančič, Mihaela Zidarn, 2020, review article Abstract: There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR[gamma]:Peroxisome proliferator-activated receptor, NF[kappa]B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2[alpha]:Elongation initiation factor 2[alpha]). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
Keywords: Covid-19, SARS-CoV-2, food, insulin resistance, obesity, Nrf2, nutrients, TRPA1
Published in DiRROS: 25.01.2021; Views: 1671; Downloads: 639
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126. Prevalence of and factors associated with healthcare-associated infections in Slovenian acute care hospitals : results of the third national surveyIrena Klavs, Mojca Serdt, Aleš Korošec, Tatjana Lejko-Zupanc, Blaž Pečavar, 2019, original scientific article Abstract: Introduction. In the third Slovenian national healthcare-associated infections (HAIs) prevalence survey, conducted within the European point prevalence survey of HAIs and antimicrobial use in acute care hospitals, we estimated the prevalence of all types of HAIs and identified factors associated with them. Methods. Patients were enrolled into a one-day cross-sectional study in November 2017. Descriptive analyses were performed to describe the characteristics of patients, their exposure to invasive procedures and the prevalence of different types of HAIs. Univariate and multivariate analyses of association of having at least one HAI with possible risk factors were performed to identify risk factors. Results. Among 5,743 patients, 4.4% had at least one HAI and an additional 2.2% were still treated for HAIs on the day of the survey, with a prevalence of HAIs of 6.6%. The prevalence of pneumoniae was the highest (1.8%), followed by surgical site infections (1.5%) and urinary tract infections (1.2%). Prevalence of blood stream infections was 0.3%. In intensive care units (ICUs), the prevalence of patients with at least one HAI was 30.6%. Factors associated with HAIs included central vascular catheter (adjusted odds ratio [aOR] 4.1; 95% confidence intervals [CI]: 3.1–5.4), peripheral vascular catheter (aOR 3.0; 95% CI: 2.3–3.9), urinary catheter (aOR 1.8; 95% CI: 1.4–2.3). Conclusions. The prevalence of HAIs in Slovenian acute care hospitals in 2017 was substantial, especially in ICUs. HAIs prevention and control is an important public health priority. National surveillance of HAIs in ICUs should be developed to support evidence-based prevention and control.
Keywords: healthcare-associated infections, prevalence, survey, risk factors, Slovenia
Published in DiRROS: 16.10.2020; Views: 2397; Downloads: 892
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127. Expression of FGFR1-4 in malignant pleural mesothelioma tissue and corresponding cell lines and its relationship to patient survival and FGFR inhibitor sensitivityGregor Vlačić, Mir Alireza Hoda, Thomas Klikovits, Katharina Sinn, Elisabeth Gschwandtner, Katja Mohorčič, Karin Schelch, Christine Pirker, Barbara Peter-Vörösmarty, Jelena Brankovic, Tanja Čufer, Aleš Rozman, Izidor Kern, 2019, original scientific article Abstract: Malignant pleural mesothelioma (MPM) is a devastating malignancy with limited therapeutic options. Fibroblast growth factor receptors (FGFR) and their ligands were shown to contribute to MPM aggressiveness and it was suggested that subgroups of MPM patients could benefit from FGFR-targeted inhibitors. In the current investigation, we determined the expression of all four FGFRs (FGFR1-FGFR4) by immunohistochemistry in tissue samples from 94 MPM patients. From 13 of these patients, we were able to establish stable cell lines, which were subjected to FGFR1-4 staining, transcript analysis by quantitative RT-PCR, and treatment with the FGFR inhibitor infigratinib. While FGFR1 and FGFR2 were widely expressed in MPM tissue and cell lines, FGFR3 and FGFR4 showed more restricted expression. FGFR1 and FGFR2 showed no correlation with clinicopathologic data or patient survival, but presence of FGFR3 in 42% and of FGFR4 in 7% of patients correlated with shorter overall survival. Immunostaining in cell lines was more homogenous than in the corresponding tissue samples. Neither transcript nor protein expression of FGFR1-4 correlated with response to infigratinib treatment in MPM cell lines. We conclude that FGFR3 and FGFR4, but not FGFR1 or FGFR2, have prognostic significance in MPM and that FGFR expression is not suffcient to predict FGFR inhibitor response in MPM cell lines.
Keywords: malignant pleural mesothelioma, fibroblast growth factor receptors, azbestos, immunotherapy, chemotherapy, genomic analysis, infigratinib
Published in DiRROS: 07.10.2020; Views: 12138; Downloads: 1029
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128. Priporočila za obravnavo bolnikov s pljučnim rakomMartina Vrankar, Nina Boc, Izidor Kern, Aleš Rozman, Karmen Stanič, Tomaž Štupnik, Mojca Unk, Maja Ebert Moltara, Vesna Zadnik, Katja Adamič, Jernej Benedik, Marko Bitenc, Jasna But-Hadžić, Anton Crnjac, Eva Ćirić, Tanja Čufer, Goran Gačevski, Marta Globočnik Kukovica, Kristina Gornik-Kramberger, Maja Ivanetič Pantar, Staša Jelerčič, Veronika Kloboves-Prevodnik, Mile Kovačević, Luka Ležaič, Mateja Marc-Malovrh, Katja Mohorčič, Bogdan Vidmar, Dušanka Vidovič, Gregor Vlačić, Ana Lina Vodušek, Rok Zbačnik, Ivana Žagar, 2020, professional article Keywords: pljučni rak, priporočila
Published in DiRROS: 22.09.2020; Views: 1891; Downloads: 712
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