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Iskalni niz: "polno besedilo" AND "organizacija" (Univerzitetna klinika za pljučne bolezni in alergijo Golnik) .

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51.
Next-generation sequencing of drug resistant Mycobacterium tuberculosis clinical isolates in low-incidence countries
Nataša Toplak, Eva Sodja, Minka Kovač, Simon Koren, Marija Žolnir-Dovč, Biljana Ilievska Poposka, Sara Truden, 2019

Povzetek: Drug resistant tuberculosis (TB), especially multidrug (MDR) and extensively drug-resistant (XDR) TB, is still a serious problem in global TB control. Slovenia and North Macedonia are low-incidence countries with TB incidence rates of 5.4 and 10.4 in 2017, respectively. In both countries, the percentage of drug resistant TB is very low with sporadic cases of MDR-TB. However, global burden of drug-resistant TB continues to increase imposing huge impact on public health systems and strongly stimulating the detection of gene variants related with drug resistance in TB. Next-generation sequencing (NGS) can provide comprehensive analysis of gene variants linked to drug resistance in Mycobacterium tuberculosis. Therefore, the aim of our study was to examine the feasibility of a full-length gene analysis for the drug resistance related genes (inhA, katG, rpoB, embB) using Ion Torrent technology and to compare the NGS results with those obtained from conventional phenotypic drug susceptibility testing (DST) in TB isolates. Between 1996 and 2017, we retrospectively selected 56 TB strains from our National mycobacterial culture collection. Of those, 33 TB isolates from Slovenian patients were isolated from various clinical samples and subjected to phenotypic DST testing in Laboratory for Mycobacteria (University Clinic Golnik, Slovenia). The remaining 23 TB isolates were isolated from Macedonian patients and sent to our laboratory for assistance in phenotypic DST testing. TB strains included were either mono-, poly- or multidrug resistant. For control purposes, we also randomly selected five TB strains susceptible to first-line anti-TB drugs. High concordance between genetic (Ion Torrent technology) and standard phenotypic DST testing for isoniazid, rifampicin and ethambutol was observed, with percent of agreement of 77%, 93.4% and 93.3%, sensitivities of 68.2%, 100% and 100%, and specificities of 100%, 80% and 88.2%, respectively. In conclusion, the genotypic DST using Ion Torrent semiconductor NGS successfully predicted drug resistance with significant shortening of time needed to obtain the resistance profiles from several weeks to just a few days.
Ključne besede: drug resistant tuberculosis, next-generation sequencing, low-incidence countries, phenotypic drug susceptibility testing
DiRROS - Objavljeno: 24.07.2020; Ogledov: 425; Prenosov: 173
URL Celotno besedilo (0,00 KB)

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Comparative analysis of prognostic histopathologic parameters in subtypes of epithelioid pleural mesothelioma
Agnes Bilecz, Paul Stockhammer, Dirk Theegarten, Izidor Kern, Marko Jakopović, Miroslav Samaržija, Thomas Klikovits, Mir Alireza Hoda, Balazs Dome, Felicitas Oberndorfer, 2020

Povzetek: Malignant pleural mesothelioma (MPM) is a rare malignancy with a dismal prognosis. While the epithelioid type is associated with a more favourable outcome, additional factors are needed to further stratify prognosis and to identify patients who can benefit from multimodal treatment. As epithelioid MPM shows remarkable morphological variability, the prognostic role of the five defined morphologies, the impact of the nuclear grading system and the mitosis-necrosis score were investigated in this study. Methods and results: Tumour specimens of 192 patients with epithelioid MPM from five European centres were histologically subtype d. Nuclear grading and mitosis–necrosi s score were determined and correlated with clinicopathological parameters and overall survival (OS). Digital slides of 55 independent cases from The Cancer Genome Atlas (TCGA) database were evaluated for external validation. Histological subtypes were collapsed into three groups based on their overlapping survival curves. The tubulopapillary/microcystic group had a significantly longer OS than the solid/trabecular group (732 days versus 397 days, P = 0.0013). Pleomorphic tumours had the shortest OS (173 days). The solid/trabecular variants showed a significant association with high nuclear grade and mitosis – necrosis score. The mitosis–necrosis score was a robust and independent prognostic factor in our patient cohort. The prognos- tic significance of all three parameters was externally validated in the TCGA cohort. Patients with tubulopapillary or microcystic tumours showed a greater improvement in OS after receiving multimodal therapy than those with solid or trabecular tumours. Conclusions: Histological subtypes of epithelioid MPM have a prognostic impact, and might help to select patients for intensive multimodal treatment approaches.
Ključne besede: epithelioid malignant pleural mesothelioma, histological subtypes
DiRROS - Objavljeno: 08.07.2020; Ogledov: 371; Prenosov: 142
URL Celotno besedilo (0,00 KB)

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Clinical significance of histologic subtyping of malignant pleural mesothelioma
Luka Brčić, Izidor Kern, 2020

Povzetek: Malignant mesothelioma (MM) is uncommon, but very aggressive tumor arising from the mesothelial cells of pleura, pericardium, peritoneum, and tunica vaginalis. Despite multimodality treatments 5-year survival is only 5% after the diagnosis. Histology and TNM staging system are still the best prognostic factors. Furthermore, histologic subtype of MM determines the clinical management of the patients. According to the 2015 WHO classification, MM is divided into diffuse, localized and well differentiated papillary mesothelioma. Major histologic subtypes of diffuse MM, namely epithelioid, biphasic and sarcomatoid, have different prognosis. However, in the last decade it has become evident that more detailed subclassification and histologic/cytological characterization of MM have prognostic and perhaps predictive implications. In this review, major histologic subtypes and cytological features of MM are presented and their relation with prognosis and predictive biomarkers is discussed.
Ključne besede: malignant mesothelioma, epithelioid malignant mesothelioma, biphasic malignant mesothelioma, sarcomatoid malignant mesothelioma
DiRROS - Objavljeno: 22.06.2020; Ogledov: 505; Prenosov: 177
URL Celotno besedilo (0,00 KB)

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