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51.
Subspecies-specific sequence detection for differentiation of Mycobacterium abscessus complex
Alina Minias, Lidia Żukowska, Jakub Lach, Tomasz Jagielski, Dominik Strapagiel, Su-Young Kim, Won-Jung Koh, Heather Adam, Ruth Bittner, Sara Truden, Marija Žolnir-Dovč, Jarosław Dziadek, 2020, original scientific article

Abstract: Mycobacterium abscessus complex (MABC) is a taxonomic group of rapidly growing, nontuberculous mycobacteria that are found as etiologic agents of various types of infections. They are considered as emerging human pathogens. MABC consists of 3 subspecies - M. abscessus subsp. bolletti, M. abscessus subsp. massiliense and M. abscessus subsp. abscessus. Here we present a novel method for subspecies differentiation of M. abscessus named Subspecies-Specific Sequence Detection (SSSD). This method is based on the presence of signature sequences present within the genomes of each subspecies of MABC. We tested this method against a virtual database of 1505 genome sequences of MABC. Further, we detected signature sequences of MABC in 45 microbiological samples through DNA hybridization. SSSD showed high levels of sensitivity and specificity for differentiation of subspecies of MABC, comparable to those obtained by rpoB sequence typing.
Keywords: Mycobacterium abscessus complex, nontuberculous mycobacteria, diagnosis
Published in DiRROS: 23.11.2020; Views: 12347; Downloads: 1236
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52.
Trans-esophageal endobronchial ultrasound-guided needle aspiration (EUS-B-NA) : a road map for the chest physician
António Bugalho, Maria De Santis, A. Szlubowski, Aleš Rozman, R. Eberhardt, 2018, review article

Abstract: The endobronchial ultrasound (EBUS) scope has been increasingly used in the gastrointestinal tract (EUS-B). Scientific data proves its efficacy and safety to provide a complete lung cancer staging, when combined with EBUS-TBNA, and in the diagnosis of para-esophageal lesions. There are multiple barriers to start performing EUS-B but probably the most important ones are related to knowledge and training, so new operators should follow a structured training curriculum. This review aims to reflect the best current knowledge regarding EUS-B and provide a road map to assist those who are incorporating the technique into their clinical practice.
Keywords: diagnosis, lymph nodes, mediastinum, non-small-cell lung carcinoma -- diagnosis, fine-needle biopsy, fine needle aspiration
Published in DiRROS: 20.11.2020; Views: 1874; Downloads: 996
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53.
The clinical relevance of oliguria in the critically ill patient : analysis of a large observational database
Jean Louis Vincent, Andrew Ferguson, Peter Pickkers, Stephan M. Jakob, Ulrich Jaschinski, Ghaleb A. Almekhlafi, Marc Leone, Majid Mokhtari, Luis E. Fontes, Philippe R. Bauer, Yasser Sakr, 2020, original scientific article

Abstract: Background: Urine output is widely used as one of the criteria for the diagnosis and staging of acute renal failure, but few studies have specifically assessed the role of oliguria as a marker of acute renal failure or outcomes in general intensive care unit (ICU) patients. Using a large multinational database, we therefore evaluated the occurrence of oliguria (defined as a urine output < 0.5 ml/kg/h) in acutely ill patients and its association with the need for renal replacement therapy (RRT) and outcome. Methods: International observational study. All adult (> 16 years) patients in the ICON audit who had a urine output measurement on the day of admission were included. To investigate the association between oliguria and mortality, we used a multilevel analysis. Results: Of the 8292 patients included, 2050 (24.7%) were oliguric during the first 24 h of admission. Patients with oliguria on admission who had at least one additional 24-h urine output recorded during their ICU stay (n = 1349) were divided into three groups: transient-oliguria resolved within 48 h after the admission day (n = 390 [28.9%]), prolonged-oliguria resolved > 48 h after the admission day (n = 141 [10.5%]), and permanent-oliguria persisting for the whole ICU stay or again present at the end of the ICU stay (n = 818 [60.6%]). ICU and hospital mortality rates were higher in patients with oliguria than in those without, except for patients with transient oliguria who had significantly lower mortality rates than non-oliguric patients. In multilevel analysis, the need for RRT was associated with a significantly higher risk of death (OR = 1.51 [95% CI 1.19%1.91], p = 0.001), but the presence of oliguria on admission was not (OR = 1.14 [95% CI 0.97%1.34], p = 0.103). Conclusions: Oliguria is common in ICU patients and may have a relatively benign nature if only transient. The duration of oliguria and need for RRT are associated with worse outcome.
Keywords: critical care, critical illness, urine, oliguria, kidney, renal insufficiency, kidney diseases, acute kidney failure, mortality, urine output, renal replacement therapy
Published in DiRROS: 18.11.2020; Views: 1891; Downloads: 1213
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54.
Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer : final analysis of the GioTag study
Maximilian J Hochmair, Alessandro Morabito, Desiree Hao, Cheng-Ta Yang, Ross A Soo, James C-H Yang, Rasim Gucalp, Balazs Halmos, Angela Märten, Tanja Čufer, 2020, original scientific article

Abstract: Aim: Final overall survival (OS) and time on treatment analysis of patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) who received sequential afatinib and osimertinib. Patients & methods: Patients (n = 203) had T790M-positive disease following first-line afatinib and started osimertinib treatment >/=10 months before data entry. Primary outcome was time on treatment; OS analysis was exploratory. Results: Median time on treatment with afatinib and osimertinib was 27.7 months (90% CI: 26.7-29.9). Median OS was 37.6 months (90% CI: 35.5-41.3); median OS was 41.6 and 44.8 months in Del19-positive patients and Asian patients, respectively. Conclusion: In real-world clinical practice, sequential afatinib and osimertinib was associated with encouraging outcomes in patients with EGFR mutation-positive NSCLC, especially in Del19-positive patients and Asian patients.
Keywords: non-small cell lung carcinoma -- therapy, drug therapy, afatinib, osimertinib, GioTag study
Published in DiRROS: 18.11.2020; Views: 1763; Downloads: 1426
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55.
Functional complement analysis can predict genetic testing results and long-term outcome in patients with complement deficiencies
Štefan Blazina, Maruša Debeljak, Mitja Košnik, Saša Simčič, Sanja Stopinšek, Gašper Markelj, Nataša Toplak, Peter Kopač, Breda Zakotnik, Marko Pokorn, Tadej Avčin, 2018, original scientific article

Abstract: Background: Prevalence of complement deficiencies (CDs) is markedly higher in Slovenian primary immunodeficiency (PID) registry in comparison to other national and international PID registries. Objective: The purposes of our study were to confirm CD and define complete and partial CD in registered patients in Slovenia, to evaluate frequency of clinical manifestations, and to assess the risk for characteristic infections separately for subjects with complete and partial CD. Methods: CD was confirmed with genetic analyses in patients with C2 deficiency, C8 deficiency, and hereditary angioedema or with repeated functional complement studies and measurement of complement components in other CD. Results of genetic studies (homozygous subjects vs. heterozygous carriers) and complement functional studies were analyzed to define complete (complement below the level of heterozygous carriers) and partial CD (complement above the level of homozygous patients). Presence of characteristic infections was assessed separately for complete and partial CD. Results: Genetic analyses confirmed markedly higher prevalence of CD in Slovenian PID registry (26% of all PID) than in other national and international PID registries (0.5–6% of all PID). Complement functional studies and complement component concentrations reliably distinguished between homozygous and heterozygous CD carriers. Subjects with partial CD had higher risk for characteristic infections than previously reported. Conclusion: Results of our study imply under-recognition of CD worldwide. Complement functional studies and complement component concentrations reliably predicted risk for characteristic infections in patients with complete or partial CD. Vaccination against encapsulated bacteria should be advocated also for subjects with partial CD and not limited to complete CD.
Keywords: complement deficiency, primary immunodeficiency, laboratory analysis, genetic analysis, clinical manifestations
Published in DiRROS: 12.11.2020; Views: 1670; Downloads: 691
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56.
Continuous glucose monitoring use and glucose variability in pre-school children with type 1 diabetes
Klemen Dovč, Kevin Cargnelutti, Anže Šturm, Julij Šelb, Nataša Bratina, Tadej Battelino, 2018, original scientific article

Abstract: Aims. The objective of this nationwide population-based cohort study was to evaluate the correlation between continuous glucose monitoring (CGM) use and glucose variability in pre-schoolers with type 1 diabetes. Methods. We analysed data from the Slovenian National Registry. The primary endpoint was the difference in glucose variability between periods, during which participants were using CGM and periods, during which CGM was not used, over 5 years. Results. A total of 40 children <8 years old were followed for an estimated observational period of 116 patient/years. Mean age at CGM initiation was 3.5 (±1.7) years. Both standard deviation of mean glucose [3.6 mmol/L (3.2–3.9) with CGM and 4.3 mmol/L (3.8–4.7) without CGM, p < 0.001] and coefficient of variation [44.0% (40.4–47.0) with CGM and 46.1% (42.3–49.4) without CGM, p = 0.021] were lower during the periods, when CGM was used. Frequent CGM use (>5 days/week) was associated with a 0.4% [4.4 mmol/mol] reduction in glycated haemoglobin level (7.6% compared to 7.2%, p = 0.047). Conclusions. Our results indicate that the use of CGM was associated with reduced glucose variability during a 5 year follow-up period among pre-schoolers with type 1 diabetes.
Keywords: continuous glucose monitoring, type 1 diabetes, children, insulin therapy
Published in DiRROS: 12.11.2020; Views: 1535; Downloads: 965
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57.
Achieving thoracic oncology data collection in Europe : a precursor study in 35 countries
Anna Rich, David R. Baldwin, Inmaculada Alfageme, Paul Beckett, Thierry Berghmans, Stephen Brincat, Otto Burghuber, Alexandru Corlateanu, Tanja Čufer, Ronald Damhuis, 2018, original scientific article

Abstract: Background: A minority of European countries have participated in international comparisons with high level data on lung cancer. However, the nature and extent of data collection across the continent is simply unknown, and without accurate data collection it is not possible to compare practice and set benchmarks to which lung cancer services can aspire. Methods: Using an established network of lung cancer specialists in 37 European countries, a survey was distributed in December 2014. The results relate to current practice in each country at the time, early 2015. The results were compiled and then verified with co-authors over the following months. Results: Thirty-five completed surveys were received which describe a range of current practice for lung cancer data collection. Thirty countries have data collection at the national level, but this is not so in Albania, Bosnia- Herzegovina, Italy, Spain and Switzerland. Data collection varied from paper records with no survival analysis, to well-established electronic databases with links to census data and survival analyses. Conclusion: Using a network of committed clinicians, we have gathered validated comparative data reporting an observed difference in data collection mechanisms across Europe. We have identified the need to develop a welldesigned dataset, whilst acknowledging what is feasible within each country, and aspiring to collect high quality data for clinical research.
Keywords: lung neoplasms -- epidemiology -- Europe, lung cancer, studies
Published in DiRROS: 12.11.2020; Views: 1452; Downloads: 655
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58.
Tuberculosis among patients treated with TNF inhibitors for rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis in slovenia : a cohort study
Žiga Rotar, Petra Svetina, Matija Tomšič, Alojzija Hočevar, Sonja Praprotnik, 2020, original scientific article

Abstract: Objectives: This study aimed to assess the risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) treated with any of the commercially available tumour necrosis factor inhibitors (TNFis) in Slovenia. Design: This is a cohort, registry (biorx.si) cross-linked with the Slovenian National TB Registry. Setting: National, involving all Slovenian rheumatology centres (six secondary and two secondary/tertiary). Participants: 2429 patients with RA, AS or PsA exposed to at least one TNFi participated in the study. Primary and secondary outcome measures: The primary outcome measures were age-adjusted and sex-adjusted TB incidence rates (IRs) and the standardised incidence ratios (SIRs) compared with the general population exploring different TNFi exposure windows. The secondary outcome measures were a detailed characterisation of the national latent tuberculosis infection (LTBI) screening and TB chemoprophylaxis protocol implementation. Results: Among the 2429 patients exposed to at least one TNFi for a total of 10 445 (49% RA, 33% AS and 18% PsA) person-years (PY), 99% completed LTBI screening and 6% required TB chemoprophylaxis. Six RA (three adalimumab, three certolizumab), two PsA (two golimumab) and zero AS patients developed TB. Five out of eight had miliary TB, three out of eight had pulmonary TB and two patients died. The age-standardised and sex-standardised TB IR (95% CI) per 100 000 PYs/SIRs (95% CI) compared with the general Slovenian population for the current TNFi exposure were 52 (0 to 110)/6.7 (0.6 to 80), 47 (0 to 110)/6.1 (0.3 to 105), 45 (0 to 109)/5.8 (0.3 to 112) overall, in RA and PsA, respectively. Conclusions: The TB IR in the Slovenian patients with RA, AS and PsA treated with TNFi was comparable with TB IRs in TB non-endemic countries with less than a tenth of the patients requiring TB chemoprophylaxis.
Keywords: epidemiology, rheumatology, tuberculosis
Published in DiRROS: 12.11.2020; Views: 1382; Downloads: 644
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59.
Sequential treatment with afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer : an observational study
Maximilian J Hochmair, Alessandro Morabito, Desiree Hao, Cheng-Ta Yang, Ross A Soo, James C-H Yang, Rasim Gucalp, Balazs Halmos, Lara Wang, Amanda Golembesky, Angela Märten, Tanja Čufer, 2018, original scientific article

Abstract: Aim: To assess outcomes in patients with EGFR mutation-positive (Del19, L858R) non-small-cell lung cancer receiving sequential afatinib and osimertinib in a real-world clinical setting. Materials & methods: In this retrospective, observational, multicenter study, patients (n = 204) had T790M-positive disease following first-line afatinib and started osimertinib treatment [>/=]10 months prior to data entry. Primary outcome was time on treatment. Results: Overall median time on treatment was 27.6 months (90% CI: 25.9-31.3), 30.3 months (90% CI: 27.6-44.5) in Del19-positive patients and 46.7 months (90% CI: 26.8-not reached) in Asians. The 2-year overall survival was 78.9%. Conclusion: In real-world clinical practice, sequential afatinib and osimertinib facilitates prolonged, chemotherapy-free treatment in patients with T790M acquired resistance, and is a potentially attractive strategy, especially for Del19-positive tumors.
Keywords: lung neoplasms -- therapy, non-small-cell lung cancer, afatinib, osimertinib, epidermal growth factor receptor, EGFR, observational study
Published in DiRROS: 09.11.2020; Views: 1726; Downloads: 1039
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60.
Epitope mapping of major ragweed allergen Amb a 1
Abida Zahirović, Borut Štrukelj, Peter Korošec, Mojca Lunder, 2019, original scientific article

Abstract: Ragweed is a prominent cause of seasonal allergies. Thus far, information on IgE-binding sites of major allergen in ragweed pollen, Amb a 1, is very limited. A powerful experimental method to gain insights on the allergen epitopes is the selection of peptides from biological libraries that bind to anti-allergen antibodies. In this work, we aimed to map IgE epitopes of Amb a 1 using epitope-mimicking short peptides % mimotopes that were affinity-selected from phage-displayed random peptide libraries. The peptides weakly aligned with the Amb a 1 primary sequence, thus suggesting that the epitopes are conformational. When the peptides were mapped onto the surface of Amb a 1 homology model, the EpiSearch analysis predicted the location of four potential epitopic sites on surface patches centred at residues K104, S110, H214, and W312. The peptides matching to the predicted epitopes bound selectively to the IgE from pool of ragweed-allergic patients% sera and therefore represent mimetics of Amb a 1 IgE epitopes. The knowledge of IgE epitopes is a prerequisite for the rational design of molecular-based approaches to diagnosis and immunotherapy of allergic diseases.
Keywords: allergens, ragweed allergy, Amb a 1, epitope mapping, phage display, mimotopes
Published in DiRROS: 09.11.2020; Views: 1527; Downloads: 1041
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