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- Köster, Jan, et al.
(författare)
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Genomic and transcriptomic features of dermatofibrosarcoma protuberans : Unusual chromosomal origin of the COL1A1-PDGFB fusion gene and synergistic effects of amplified regions in tumor development
- 2020
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Ingår i: Cancer Genetics. - : ELSEVIER SCIENCE INC. - 2210-7762 .- 2210-7770. ; 241, s. 34-41
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Tidskriftsartikel (refereegranskat)abstract
- The dermatofibrosarcoma protuberans family of tumors (DPFT) comprises cutaneous soft tissue neoplasms associated with aberrant PDGFBR signaling, typically through a COL1A1-PDGFB fusion. The aim of the present study was to obtain a better understanding of the chromosomal origin of this fusion and to assess the spectrum of secondary mutations at the chromosome and nucleotide levels. We thus investigated 42 tumor samples from 35 patients using chromosome banding, fluorescence in situ hybridization, single nucleotide polymorphism arrays, and/or massively parallel sequencing (gene panel, whole exome and transcriptome sequencing) methods. We confirmed the age-associated differences in the origin of the COL1A1-PDGFB fusion and could show that it in most cases must arise after DNA synthesis, i.e., in the S or G2 phase of the cell cycle. Whereas there was a non-random pattern of secondary chromosomal rearrangements, single nucleotide variants seem to have little impact on tumor progression. No clear genomic differences between low-grade and high-grade DPFT were found, but the number of chromosomes and chromosomal imbalances as well as the frequency of 9p deletions all tended to be greater among the latter. Gene expression profiling of tumors with COL1A1-PDGFB fusions associated with unbalanced translocations or ring chromosomes identified several transcriptionally up-regulated genes in the amplified regions of chromosomes 17 and 22, including TBX2, PRKCA, MSI2, SOX9, SOX10, and PRAME.
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| 2. |
- Sjöström, Björn, et al.
(författare)
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Characteristics and definitive outcomes of COVID-19 patients admitted to a secondary hospital intensive care unit in Sweden
- 2021
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Ingår i: Health Science Reports. - : John Wiley & Sons. - 2398-8835. ; 4:4
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Most published reports of COVID-19 Intensive Care Unit (ICU) patients are from large tertiary hospitals and often present short-term or incomplete outcome data. There are reports indicating that ICUs with fewer beds are associated with higher mortality. This study aimed to investigate the definitive outcome and patient characteristics of the complete first wave of COVID-19 patients admitted to ICU in a secondary hospital.Methods: In this prospective observational study, all patients with respiratory failure and a positive SARS-CoV-2 test admitted to Västerås Hospital ICU between 24 March and July 22, 2020 were included. The primary outcome was defined as 90-day mortality. Secondary outcomes included ICU length of stay, hospital length of stay, number of days with invasive ventilation, need for vasopressors/inotropes, and use of renal replacement therapy.Results: Fifty-three patients were included. Median age (range) was 59 (33-76) and 74% were men. Obesity and hypertension were the most common comorbidities and 45% of the patients were born outside Europe. Ninety-day mortality was 30%. Median ICU length of stay (interquartile range) was 14 (5-24) days and the duration of invasive mechanical ventilation 16 (12-26) days. No patients received dialysis at 90-day follow-up.Conclusion: In this cohort of COVID-19 patients treated in a secondary hospital ICU, mortality rates were low compared to early studies from China, Italy, and the United States, but similar to other government-funded hospitals in Scandinavia. A preparatory reorganization enabled an increase in ICU capacity, hence avoiding an overwhelmed intensive care organization.
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| 3. |
- Viklund, Emilia, et al.
(författare)
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Current smoking alters phospholipid- and surfactant protein A levels in small airway lining fluid: An explorative study on exhaled breath
- 2021
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 16:6
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Tidskriftsartikel (refereegranskat)abstract
- Small airways are difficult to access. Exhaled droplets, also referred to as particles, provide a sample of small airway lining fluid and may reflect inflammatory responses. We aimed to explore the effect of smoking on the composition and number of exhaled particles in a smoker-enriched study population. We collected and chemically analyzed exhaled particles from 102 subjects (29 never smokers, 36 former smokers and 37 current smokers) aged 39 to 83 years (median 63). A breathing maneuver maximized the number exhaled particles, which were quantified with a particle counter. The contents of surfactant protein A and albumin in exhaled particles was quantified with immunoassays and the contents of the phospholipids dipalmitoyl- and palmitoyl-oleoyl- phosphatidylcholine with mass spectrometry. Subjects also performed spirometry and nitrogen single breath washout. Associations between smoking status and the distribution of contents in exhaled particles and particle number concentration were tested with quantile regression, after adjusting for potential confounders. Current smokers, compared to never smokers, had higher number exhaled particles and more surfactant protein A in the particles. The magnitude of the effects of current smoking varied along the distribution of each PEx-variable. Among subjects with normal lung function, phospholipid levels were elevated in current smokers, in comparison to no effect of smoking on these lipids at abnormal lung function. Smoking increased exhaled number of particles and the contents of lipids and surfactant protein A in the particles. These findings might reflect early inflammatory responses to smoking in small airway lining fluid, also when lung function is within normal limits.
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