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1.
Results of screening in early and advanced thoracic malignancies in the EORTC pan-European SPECTAlung platform
Marie Morfouace, Silvia Novello, A. Stevovic, C. Dooms, Urška Janžič, Thierry Berghmans, Rafal Dziadziuszko, T. Gorlia, Enriqueta Felip, Benjamin Besse, 2022, izvirni znanstveni članek

Povzetek: Access to a comprehensive molecular alteration screening is patchy in Europe and quality of the molecular analysis varies. SPECTAlung was created in 2015 as a pan-European screening platform for patients with thoracic malignancies. Here we report the results of almost 4 years of prospective molecular screening of patients with thoracic malignancies, in terms of quality of the program and molecular alterations identified. Patients with thoracic malignancies at any stage of disease were recruited in SPECTAlung, from June 2015 to May 2019, in 7 different countries. Molecular tumour boards were organised monthly to discuss patients' molecular and clinical profile and possible biomarker-driven treatments, including clinical trial options. FFPE material was collected and analysed for 576 patients with diagnosis of pleural, lung, or thymic malignancies. Ultimately, 539 patients were eligible (93.6%) and 528 patients were assessable (91.7%). The turn-around time for report generation and molecular tumour board was 214 days (median). Targetable molecular alterations were observed in almost 20% of cases, but treatment adaptation was low (3% of patients). SPECTAlung showed the feasibility of a pan-European screening platform. One fifth of the patients had a targetable molecular alteration. Some operational issues were discovered and adapted to improve efficiency.
Ključne besede: thoracic neoplasms -- Europe, lung neoplasms -- Europe, diagnostic screening programs -- Europe, malignancies, lung cancer
Objavljeno v DiRROS: 24.06.2022; Ogledov: 81; Prenosov: 55
.pdf Celotno besedilo (4,21 MB)
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COVID-19 pandemic impact on cytopathology practice in the post-lockdown period : an international, multicenter study
Elena Vigliar, Pasquale Pisapia, Filippo Dello Iacovo, Izidor Kern, William C. Faquin, Martha Bishop Pitman, 2022, izvirni znanstveni članek

Povzetek: Background. In a previous worldwide survey, the authors showed a drastic reduction in the number of cytological specimens processed during the coronavirus disease 2019 “lockdown” period along with an increase in malignancy rates. To assess the continued impact of the pandemic on cytological practices around the world, they undertook a second follow-up worldwide survey collecting data from the post-lockdown period (2020). Methods. Participants were asked to provide data regarding their cytopathology activity during the first 12 weeks of their respective national post-lockdown period (2020), which ranged from April 4 to October 31. Differences between the post-lockdown period and the corresponding 2019 period were evaluated, and the authors specifically focused on rates of malignant diagnoses. Results. A total of 29 respondents from 17 countries worldwide joined the survey. Overall, a lower number of cytological specimens (n = 236,352) were processed in comparison with the same period in 2019 (n = 321,466) for a relative reduction of 26.5%. The overall malignancy rate showed a statistically significant increase (12,442 [5.26%] vs 12,882 [4.01%]; P < .001) during the same time period. Similar results were obtained if both malignancy and suspicious for malignancy rates were considered together (15,759 [6.58%] vs 16,011 [4.98%]; P < .001). Conclusions. The data showed a persistent reduction in the cytological specimen volume during the post-lockdown period (2020). However, the relative increase in the cytological workload in the late part of the post-lockdown is a promising finding of a slow return to normality.
Ključne besede: covid-19, neoplasms, early detection of cancer, lung -- pathology -- cytology, diagnostic screening programs, fine-needle biopsy, cytopathology, fine-needle aspiration, malignancy rate
Objavljeno v DiRROS: 07.02.2022; Ogledov: 199; Prenosov: 44
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NSCLC molecular testing in Central and Eastern European countries
Ales Ryška, Peter Berzinec, Luka Brčić, Tanja Čufer, Rafal Dziadziuszko, Maya Gottfried, Ilona Kovalszky, Włodzimierz Olszewski, Buge Oz, Lukas Plank, József Tímár, 2018, izvirni znanstveni članek

Povzetek: Background: The introduction of targeted treatments for subsets of non-small cell lung cancer (NSCLC) has highlighted the importance of accurate molecular diagnosis to determine if an actionable genetic alteration is present. Few data are available for Central and Eastern Europe (CEE) on mutation rates, testing rates, and compliance with testing guidelines. Methods: A questionnaire about molecular testing and NSCLC management was distributed to relevant specialists in nine CEE countries, and pathologists were asked to provide the results of EGFR and ALK testing over a 1-year period. Results: A very high proportion of lung cancer cases are confirmed histologically/cytologically (75-100%), and molecular testing of NSCLC samples has been established in all evaluated CEE countries in 2014. Most countries follow national or international guidelines on which patients to test for EGFR mutations and ALK rearrangements. In most centers at that time, testing was undertaken on request of the clinician rather than on the preferred reflex basis. Immunohistochemistry, followed by fluorescent in situ hybridization confirmation of positive cases, has been widely adopted for ALK testing in the region. Limited reimbursement is a significant barrier to molecular testing in the region and a disincentive to reflex testing. Multidisciplinary tumor boards are established in most of the countries and centers, with 75-100% of cases being discussed at a multidisciplinary tumor board at specialized centers. Conclusions: Molecular testing is established throughout the CEE region, but improved and unbiased reimbursement remains a major challenge for the future. Increasing the number of patients reviewed by multidisciplinary boards outside of major centers and access to targeted therapy based on the result of molecular testing are other major challenges.
Ključne besede: non-small-cell lung carcinoma, molecular diagnostic techniques, EGFR mutations, ALK rearrangements, Central Europe, Eastern Europe
Objavljeno v DiRROS: 30.11.2020; Ogledov: 927; Prenosov: 463
.pdf Celotno besedilo (373,86 KB)
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Non-small cell lung cancer in countries of Central and Southeastern Europe : diagnostic procedures and treatment reimbursement surveyed by the Central European Cooperative Oncology Group
Ales Ryška, Rares Buiga, Albena Fakirova, Izidor Kern, Włodzimierz Olszewski, Lukas Plank, Sven Seiwerth, Erika Toth, Eri Zivka, Christiane Thallinger, Christoph Zielinski, Luka Brčić, 2018, izvirni znanstveni članek

Povzetek: This article analyzes the availability of different diagnostic procedures of non-small cell lung cancer (NSCLC) and the reimbursement landscape of drugs for NSCLC in countries of central and southeastern Europe (CEE). A survey was conducted by the Central European Cooperative Oncology Group. Results of the survey show that both availability and reimbursement of diagnoses of molecular alterations in NSCLC, the detection of which is essential for therapeutic decisions, varies widely between countries of CEE. Not only is "reflex" testing often substituted by analyses performed only "on demand," but reimbursement of such assessments varies widely between unavailability and payments by the health care system or even pharmaceutical companies. It was concluded that a structured access to testing and reimbursement should be the aim in order to provide patients with appropriate therapeutic options. Implications for Practice. This article provides an overview of the limitations in lung cancer treatment in countries of central and southeastern Europe, as well as the reimbursement status of various lung cancer treatment regimens in these countries, which directly impacts treatment options.
Ključne besede: Non-small cell lung carcinoma -- diagnosis -- economics -- Europe, molecular diagnostic techniques, precision medicine, Central Europe, Southeastern Europe, reimbursement
Objavljeno v DiRROS: 09.11.2020; Ogledov: 863; Prenosov: 189
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Recombinant glycoproteins resembling carbohydrate-specific IgE epitopes from plants, venoms and mites
Pia Gattinger, Irene Mittermann, Christian Lupinek, Gerhard Hofer, Walter Keller, Urška Bidovec, Peter Korošec, Christine Koessler, Natalija Novak, Rudolf Valenta, 2019, izvirni znanstveni članek

Povzetek: Background: N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity. Objectives: To engineer recombinant glycoproteins resembling carbohydrate-specific IgE epitopes from venoms, pollen and mites which can discriminate carbohydrate-specific IgE from allergenic, peptide-specific IgE. Methods: One or two N-glycosylation sites were engineered into the N-terminus of the non-allergenic protein horse heart myoglobin (HHM) using synthetic gene technology. HHM 1 and HHM 2 containing one or two N-glycosylation sites were expressed in baculovirus-infected High-FiveTM insect cells and a non-glycosylated version (HHM 0) was obtained by mutating the glycosylation motif. Recombinant HHM proteins were analyzed regarding fold and aggregation by circular dichroism and gel filtration, respectively. IgE reactivity was assessed by ELISA, immunoblotting and quantitative ImmunoCAP measurements. IgE inhibition assays were performed to study cross-reactivity with venom, plant and mite-derived carbohydrate IgE epitopes. Results: HHM-glycovariants were expressed and purified from insect cells as monomeric and folded proteins. The HHM-glycovariants exhibited strictly carbohydrate-specific IgE reactivity, designed to quantify carbohydrate specific IgE and resembled IgE epitopes of pollen, venom and mite-derived carbohydrates. IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2. Conclusion: Defined recombinant HHM-glycoproteins resembling carbohydrate-specific IgE epitopes from plants, venoms and mites were engineered which made it possible to discriminate carbohydrate- from peptide-specific IgE reactivity.
Ključne besede: allergy and immunology, allergens, glycoproteins, molecular diagnostic technique, recombinant glycoproteins, molecular allergology, component-resolved diagnosis
Objavljeno v DiRROS: 16.10.2020; Ogledov: 917; Prenosov: 625
.pdf Celotno besedilo (2,07 MB)
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Outsourcing predictive biomarker testing in non-small cell carcinoma : a personal view of pathologists
Luka Brčić, Izidor Kern, 2020, kratki znanstveni prispevek

Ključne besede: non-small cell lung carcinoma, diagnostic pathology, predictive biomarkers
Objavljeno v DiRROS: 27.07.2020; Ogledov: 1237; Prenosov: 663
.pdf Celotno besedilo (139,69 KB)
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