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81.
Genomic insights into the Mycobacterium kansasii complex : an update
Tomasz Jagielski, Paulina Borówka, Zofia Bakuła, Jakub Lach, Błażej Marciniak, Anna Brzostek, Jarosław Dziadek, Mikołaj Dziurzyński, Lian Pennings, Jakobus van Ingen, Marija Žolnir-Dovč, Dominik Strapagiel, 2020, izvirni znanstveni članek

Povzetek: Only very recently, has it been proposed that the hitherto existing Mycobacteriumkansasii subtypes (I–VI) should be elevated, each, to a species rank. Consequently, the former M. kansasii subtypes have been denominated as Mycobacterium kansasii (former type I), Mycobacterium persicum (II), Mycobacterium pseudokansasii (III), Mycobacterium innocens (V), and Mycobacterium attenuatum (VI). The present work extends the recently published findings by using a three-pronged computational strategy, based on the alignment fraction-average nucleotide identity, genome-to-genome distance, and core-genome phylogeny, yet essentially independent and much larger sample, and thus delivers a more refined and complete picture of the M. kansasii complex. Furthermore, five canonical taxonomic markers were used, i.e., 16S rRNA, hsp65, rpoB, and tuf genes, as well as the 16S-23S rRNA intergenic spacer region (ITS). The three major methods produced highly concordant results, corroborating the view that each M. kansasii subtype does represent a distinct species. This work not only consolidates the position of five of the currently erected species, but also provides a description of the sixth one, i.e., Mycobacterium ostraviense sp. nov. to replace the former subtype IV. By showing a close genetic relatedness, amonophyletic origin, and overlapping phenotypes, our findings support the recognition of the M. kansasii complex (MKC), accommodating all M. kansasii-derived species and Mycobacterium gastri. None of the most commonly used taxonomic markers was shown to accurately distinguish all the MKC species. Likewise, no species-specific phenotypic characteristics were found allowing for species differentiation within the complex, except the non-photochromogenicity of M. gastri. To distinguish, most reliably, between the MKC species, and between M. kansasii and M. persicum in particular, whole-genome-based approaches should be applied. In the absence of clear differences in the distribution of the virulence-associated region of difference 1 genes among the M. kansasii-derived species, the pathogenic potential of each of these species can only be speculatively assessed based on their prevalence among the clinically relevant population. Large-scale molecular epidemiological studies are needed to provide a better understanding of the clinical significance and pathobiology of the MKC species. The results of the in vitro drug susceptibility profiling emphasize the priority of rifampicin administration in the treatment of MKC-induced infections, while undermining the use of ethambutol, due to a high resistance to this drug.
Ključne besede: Mycobacteriumkansasii complex, Mycobacteriumostraviense sp. nov., non-tuberculous mycobacteria (NTM), whole genome sequencing, taxonomy
Objavljeno v DiRROS: 31.07.2020; Ogledov: 1846; Prenosov: 1317
.pdf Celotno besedilo (10,22 MB)
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82.
Towards personalization of asthma treatment according to trigger factors
Katarzyna Niespodziana, Kristina Borochova, Petra Pazderova, Thomas Schlederer, Natalia Astafyeva, Tatiana Baranovskaya, Mohamed-Ridha Barbouche, Evgenyi Beltiukov, Angelika Berger, Elena Borzova, Jean Bousquet, Mihaela Zidarn, Rudolf Valenta, 2020, izvirni znanstveni članek

Povzetek: Asthma is a severe and chronic disabling disease affecting more than 300 million people world-wide. While in the past few drugs for treatment of asthma were available, new treatment options are currently emerging which appear to be highly effective in certain subgroups of patients. Accordingly there is a need for biomarkers which allow selection of patients for refined and personalized treatment strategies. Recently, serological chip tests based on micro-arrayed allergen molecules and peptides derived from the most common rhinovirus strains have been developed which may discriminate two of the most common forms of asthma, i.e., allergen- and virus-triggered asthma. In this perspective we argue that classification of asthma patients according to these common trigger factors may open new possibilities for personalized management of asthma.
Ključne besede: allergy and immunology, asthma, signs and symptoms, respiratory, rhinovirus, allergens, microarray analysis, precision medicine, wheeze
Objavljeno v DiRROS: 31.07.2020; Ogledov: 2242; Prenosov: 1082
.pdf Celotno besedilo (292,51 KB)
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83.
Pulmonary pathology and COVID-19 : lessons from autopsy : the experience of European pulmonary pathologists
Fiorella Calabrese, Federica Pezzuto, Francesco Fortarezza, Paul Hofman, Izidor Kern, Angel Panizo, Jan von der Thüsen, Sergei Timofeev, Gregor Gorkiewicz, Francesca Lunardi, 2020, izvirni znanstveni članek

Povzetek: Since its initial recognition in December 2019, Coronavirus disease 19 (COVID-19) has quickly spread to a pandemic infectious disease. The causative agent has been recognized as a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily affecting the respiratory tract. To date, no vaccines are available nor any specific treatment. To limit the number of infections, strict directives have been issued by governments that have been translated into equally rigorous guidelines notably for post-mortem examinations by international and national scientific societies. The recommendations for biosafety control required during specimen collection and handling have strongly limited the practice of autopsies of the COVID-19 patients to a few adequate laboratories. A full pathological examination has always been considered an important tool to better understand the pathophysiology of diseases, especially when the knowledge of an emerging disorder is limited and the impact on the healthcare system is significant. The first evidence of diffuse alveolar damage in the context of an acute respiratory distress syndrome has now been joined by the latest findings that report a more complex scenario in COVID-19, including a vascular involvement and a wide spectrum of associated pathologies. Ancillary tools such as electron microscopy and molecular biology used on autoptic tissue samples from autopsy are also significantly contributing to confirm and/or identify new aspects useful for a deeper knowledge of the pathogenetic mechanisms. This article will review and summarize the pathological findings described in COVID-19 until now, chiefly focusing on the respiratory tract, highlighting the importance of autopsy towards a better knowledge of this disease.
Ključne besede: COVID-19, SARS-CoV-2, autopsy, lung, pandemic
Objavljeno v DiRROS: 31.07.2020; Ogledov: 13253; Prenosov: 1120
.pdf Celotno besedilo (1,55 MB)
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84.
Heat shock protein 27 as a predictor of prognosis in patients admitted to hospital with acute COPD exacerbation
Matthias Zimmermann, Denise Traxler, Christine Bekos, Elisabeth Simader, Thomas Mueller, Alexandra Graf, Mitja Lainščak, Robert Marčun, Mitja Košnik, Matjaž Fležar, Aleš Rozman, Peter Korošec, 2020, izvirni znanstveni članek

Povzetek: Episodes of acute exacerbations are major drivers of hospitalisation and death from COPD. To date, there are no objective biomarkers of disease activity or biomarkers to predict patient outcome. In this study, 211 patients hospitalised for an acute exacerbation of COPD have been included. At the time of admission,routine blood tests have been performed including complete blood count, C-reactive protein, cardiac troponin T and NT-proBNP. Heat shock protein 27 (HSP27) serum concentrations were determined at time of admission, discharge and 180 days after discharge by ELISA. We were able to demonstrate significantly increased HSP27 serum concentrations in COPD patients at time of admission to hospital as compared to HSP27 concentrations obtained 180 days after discharge. In univariable Cox regression analyses, a HSP27 serum concentration >/= 3098 pg/mL determined at admission was a predictor of all-cause mortality at 90 days, 180 days, 1 year and 3 years. In multivariable analyses, an increased HSP27 serum concentration at admission retained its prognostic ability with respect to all-cause mortality for up to 1year follow-up. However, an increased HSP27 serum concentration at admission was not an independent predictor of long-term all-cause mortality at 3 years. Elevated serum HSP27 concentrations significantly predicted short-term mortality in patients admitted to hospital with acute exacerbation of COPD and could help to improve outcomes by identifying high-risk patients.
Ključne besede: COPD, acute exacerbation, disease activity
Objavljeno v DiRROS: 29.07.2020; Ogledov: 1661; Prenosov: 1031
.pdf Celotno besedilo (679,90 KB)
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85.
Coping strategies of patients with advanced lung or colorectal cancer in six European countries : insights from the ACTION study
Lea J. Jabbarian, Ida Joanna Korfage, Branka Červ, Johannes JM van Delden, Luc Deliens, Guido Miccinesi, Sheila Payne, Anna Thit Johnsen, Mariette Verkissen, Andrew Wilcock, Agnes van der Heide, Judith Anna Catharina Rietjens, 2020, pregledni znanstveni članek

Povzetek: Objective: Even when medical treatments are limited, supporting patients' coping strategies could improve their quality of life. Greater understanding of patients' coping strategies, and influencing factors, can aid developing such support. We examined the prevalence of coping strategies and associated variables. Methods: We used sociodemographic and baseline data from the ACTION trial, including measures of Denial, Acceptance and Problem-focused coping (COPE; Brief COPE inventory), of patients with advanced cancer from six European countries. Clinicians provided clinical information. Linear mixed models with clustering at hospital level were used. Results: Data from 675 patients with stage III/ IV lung (342, 51%) or stage IV colorectal (333, 49%) cancer were used; mean age 66 (10 SD) years. Overall, patients scored low on Denial and high on Acceptance and Problem-focused coping. Older age was associated with higher scores on Denial than younger age ([beta] = 0.05; CI[0.023; 0.074]), and patients from Italy ([beta] = 1.57 CI[0.760; 2.388]) and Denmark ([beta] = 1.82 CI[0.881; 2.750]) scored higher on Denial than patients in other countries. Conclusions: Patients with advanced cancer predominantly used Acceptance and Problem-focused coping, and Denial to a lesser extent. Since the studied coping strategies of patients with advanced cancer vary between subpopulations, we recommend taking these factors into account when developing tailored interventions to support patients' coping strategies.
Ključne besede: ACTION study, lung cancer, colorectal cancer, coping strategies
Objavljeno v DiRROS: 29.07.2020; Ogledov: 1648; Prenosov: 1112
.pdf Celotno besedilo (319,54 KB)
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86.
Completeness of tuberculosis (TB) notification : inventory studies and capture-recapture analyses, six European Union countries, 2014 to 2016
Masja Straetemans, Mirjam I Bakker, Sandra Alba, Christina Mergenthaler, Ente Rood, Peter H Andersen, Henrieke Schimmel, Aleksandar Šimunović, Petra Svetina, Carlos Carvalho, 2020, izvirni znanstveni članek

Povzetek: Background. Progress towards the World Health Organization's End TB Strategy is monitored by assessing tuberculosis (TB) incidence, often derived from TB notification, assuming complete case detection and reporting. This assumption is unlikely to hold in many settings, including European Union (EU) countries. Aim. We aimed to assess observed and estimated completeness of TB notification through inventory studies and capture-recapture (CRC) methodology in six EU countries: Croatia, Denmark, Finland, the Netherlands, Portugal, Slovenia. Methods. We performed record linkage, case ascertainment and CRC analyses of data collected retrospectively from at least three national TB-related registers in each country between 2014 and 2016. Results. Observed completeness of TB notification by inventory studies was 73.9% in Croatia, 98.7% in Denmark, 83.6% in Finland, 81.6% in the Netherlands, 85.8% in Portugal and 100% in Slovenia. Subsequent CRC analysis estimated completeness of TB notification to be 98.4% in Denmark, 76.5% in Finland and 77.0% in Portugal. In Croatia, CRC analyses produced implausible results while in the Netherlands and Slovenia, it was methodologically considered not meaningful. Conclusion. Inventory studies and CRC methodology suggest a TB notification completeness between 73.9% and 100% in the six EU countries. Mandatory reporting by clinicians and laboratories, and cross-checking of registers, strongly contributes to accurate notification rates, but hospital episode registers likely contain a considerable proportion of false-positive TB records and are thus less useful. Further strengthening routine surveillance to count TB cases, i.e. incidence, accurately by employing record-linkage of high-quality TB registers should make CRC studies obsolete in EU countries.
Ključne besede: Mycobacterium tuberculosis, tuberculosis, incidence, public health surveillance, registries, reporting, notification, data collection, data analysis
Objavljeno v DiRROS: 27.07.2020; Ogledov: 1454; Prenosov: 1034
.pdf Celotno besedilo (214,77 KB)
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87.
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: 2054; Prenosov: 1061
.pdf Celotno besedilo (139,69 KB)
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88.
Access to novel drugs for non-small cell lung cancer in Central and Southeastern Europe : a Central European Cooperative Oncology Group analysis
Tanja Čufer, Tudor Ciuleanu, Peter Berzinec, Gabriela Galffy, Marko Jakopović, Jacek Jassem, Dragana Jovanovic, Zhasmina MIhaylova, Gyula Ostoros, Christiane Thallinger, Milada Zemanova, Christoph Zielinski, 2020, izvirni znanstveni članek

Povzetek: Background. Treatment of non-small cell lung cancer (NSCLC) improved substantially in the last decades. Novel targeted and immune-oncologic drugs were introduced into routine treatment. Despite accelerated development and subsequent drug registrations by the European Medicinal Agency (EMA), novel drugs for NSCLC are poorly accessible in Central and Eastern European (CEE) countries. Material and Methods. The Central European Cooperative Oncology Group conducted a survey among experts from 10 CEE countries to provide an overview on the availability of novel drugs for NSCLC and time from registration to reimbursement decision in their countries. Results. Although first-generation epidermal growth factor receptor tyrosine kinase inhibitors were reimbursed and available in all countries, for other registered therapies - even for ALK inhibitors and checkpoint inhibitors in first-line - there were apparent gaps in availability and/or reimbursement. There was a trend for better availability of drugs with longer time from EMA marketing authorization. Substantial differences in access to novel drugs among CEE countries were observed. In general, the availability of drugs is not in accordance with the Magnitude of Clinical Benefit Scale (MCBS), as defined by the European Society for Medical Oncology (ESMO). Time spans between drug registrations and national decisions on reimbursement vary greatly, from less than 3 months in one country to more than 1 year in the majority of countries. Conclusion. The access to novel drugs for NSCLC in CEE countries is suboptimal. To enable access to the most effective compounds within the shortest possible time, reimbursement decisions should be faster and ESMO MCBS should be incorporated into decision making.
Ključne besede: non-small cell lung cancer, treatment, novel drugs, Central Europe, Southeastern Europe
Objavljeno v DiRROS: 24.07.2020; Ogledov: 1790; Prenosov: 1050
.pdf Celotno besedilo (341,24 KB)
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89.
Next-generation sequencing of drug resistant Mycobacterium tuberculosis clinical isolates in low-incidence countries
Eva Sodja, Nataša Toplak, Simon Koren, Minka Kovač, Sara Truden, Biljana Ilievska Poposka, Marija Žolnir-Dovč, 2019, izvirni znanstveni članek

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
Objavljeno v DiRROS: 24.07.2020; Ogledov: 1820; Prenosov: 1024
.pdf Celotno besedilo (144,02 KB)
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90.
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