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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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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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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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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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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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