The QuantiFERON-TB-Gold Test (QFT) is more specific than the Mantoux skin-test to discriminate between Mycobacterium tuberculosis (MTB) and non-tuberculous mycobacterial (NTM) infections. Here we ...study the performance of the QFT in patients with NTM disease.
From 2005 to 2011, nationwide patient data on positive NTM cultures (n = 925) were combined with nationwide data on QFT results (n = 16,133), both retrieved from the International Reference Laboratory of Mycobacteriology, Denmark. A total of 112 patients with NTM infections had a QFT performed, 53 patients had definite NTM disease, 10 had possible disease and 49 had NTM colonization.
QFT was positive in 8% (4/53) of patients with definite disease, 40% (4/10) with possible disease and 31% (15/49) with colonization. Positivity rate was lowest among patients with definite disease infected with NTM without the RD1 region 4% (2/50). None of the 15 children with MAC lymphadenitis had a positive QFT.
This study is one of the largest assessing IGRAs in patients with NTM disease in a TB low-incidence setting. Our study showed that the QFT holds potential to discriminate between NTM and MTB infections. We found no positive IGRA test results among children with NTM not sharing the RD1-region of MTB resulting in a 100% specificity and we suggest that a QFT in a child presenting with cervical lymphadenitis may be helpful in distinguishing NTM from TB lymphadenitis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There is limited knowledge about non-tuberculous mycobacteria (NTM) infections in migrants. We aimed to assess the incidence and clinical significance of NTM among migrants in Denmark.
Nationwide ...register-based cohort study of migrants with a positive NTM culture in Denmark from 1991 through 2021, stratified by patient demographics, disease localisation, species, and clinical significance.
433 migrants had a positive NTM culture, resulting in an overall incidence rate (IR) of 3.7 (95%CI 3.3–4.0) per 100,000 migrants. Overall NTM IRs for definite disease were 1.0 (95%CI 0.9–1.2), possible disease 1.0 (95%CI 0.8–1.2), and isolation 1.7 (95%CI 1.4–1.9) per 100,000 migrants. Migrants had considerably higher age- and sex-adjusted NTM IRs of positive cultures (incidence rate ratio IRR = 2.1, 95%CI 1.9–2.3, p < 0.001), possible disease (IRR = 2.4, 95%CI 2.0–3.0, p < 0.001), and isolation (IRR = 4.6, 95%CI 3.9–5.4, p < 0.001) compared to Danish-born, but not of definite disease (IRR = 1.1, 95%CI 0.9–1.3, p = 0.562). IRs of migrants with positive NTM cultures did not increase over time (−0.8 %/year, p = 0.133).
Migrants have a higher, but stable, burden of NTM compared with Danish-born. The higher rates likely reflect that more specimens are examined for Mycobacterium tuberculosis. Microbiologically classified definite NTM disease is not substantially more common among migrants.
•Migrants in Denmark have a higher burden of NTM infection than Danish-born.•Definite NTM disease (microbiologically defined) is not more common among migrants.•Migrants with NTM are younger compared with Danish-born.•Positive NTM cultures have not increased over time for migrants in Denmark.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
False negative and indeterminate Interferon Gamma Release Assay (IGRA) results are a well documented problem. Cigarette smoking is known to increase the risk of tuberculosis (TB) and to impair ...Interferon-gamma (IFN-γ) responses to antigenic challenge, but the impact of smoking on IGRA performance is not known. The aim of this study was to evaluate the effect of smoking on IGRA performance in TB patients in a low and high TB prevalence setting respectively.
Patients with confirmed TB from Denmark (DK, n = 34; 20 smokers) and Tanzania (TZ, n = 172; 23 smokers) were tested with the QuantiFERON-TB Gold In tube (QFT). Median IFN-γ level in smokers and non smokers were compared and smoking was analysed as a risk factor for false negative and indeterminate QFT results.
Smokers from both DK and TZ had lower IFN-γ antigen responses (median 0.9 vs. 4.2 IU/ml, p = 0.04 and 0.4 vs. 1.6, p < 0.01), less positive (50 vs. 86%, p = 0.03 and 48 vs. 75%, p < 0.01) and more false negative (45 vs. 0%, p < 0.01 and 26 vs. 11%, p = 0.04) QFT results. In Tanzanian patients, logistic regression analysis adjusted for sex, age, HIV and alcohol consumption showed an association of smoking with false negative (OR 17.1, CI: 3.0-99.1, p < 0.01) and indeterminate QFT results (OR 5.1, CI: 1.2-21.3, p = 0.02).
Cigarette smoking was associated with false negative and indeterminate IGRA results in both a high and a low TB endemic setting independent of HIV status.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The ability of interferon-γ release assays to predict the development of TB has been investigated in many studies, but few cases develop TB during follow-up limiting the generalisation of results.
We ...assessed QuantiFERON-TB Gold In-Tube test (QFT) results from 15 980 Danish individuals and data on all TB cases in Denmark from 2005 to 2012 and determined the predictive value of the QFT for coprevalent TB (0-90 days after testing) and incident TB (>90 days).
Coprevalent TB was diagnosed in 10.7% (183/1703) and 0.3% (38/13 463) cases with a positive and negative QFT, respectively. For the QFT-positive cases, coprevalent TB was more frequent among persons <35 years compared with those >35 years (19.3% vs 7.2%, p<0.001). The cohort was followed-up for 52 807 person-years, median follow-up time was 3.36 years. For incident TB, the positive and negative predictive values (PPV and NPV) were 1.32% and 99.85%, respectively. Incidence rates (IR) for incident TB among QFT-positives and QFT-negatives were 383 per 10(5) and 45 per 10(5) person-years, respectively. Among cases with a positive QFT, IR for incident TB was associated with time interval since QFT (<2 years, p<0.001), but not with age (<35 years, p=0.087).
We confirmed a high NPV of the QFT and found positive QFT associated with a higher risk of subsequent incident TB. Overall, the PPV for incident cases was 1.32%, and development of incident TB was associated with time interval after the QFT, but not with age.
In recent decades, an increasing incidence of pulmonary infections with non-tuberculous mycobacteria has been reported, primarily affecting patients with structural lung diseases and/or ...immunosuppression. In Denmark, approximately 100 new cases of infection with non-tuberculous mycobacteria occur yearly, most commonly with Mycobac-terium avium complex. Diagnosis is based on clinical, radiological and microbiological criteria. Treatment is difficult, and outcomes are often poor. Antibiotic treatment should be performed by specialists with reference to international guidelines.
The whole-genome duplication 80 million years ago of the common ancestor of salmonids (salmonid-specific fourth vertebrate whole-genome duplication, Ss4R) provides unique opportunities to learn about ...the evolutionary fate of a duplicated vertebrate genome in 70 extant lineages. Here we present a high-quality genome assembly for Atlantic salmon (Salmo salar), and show that large genomic reorganizations, coinciding with bursts of transposon-mediated repeat expansions, were crucial for the post-Ss4R rediploidization process. Comparisons of duplicate gene expression patterns across a wide range of tissues with orthologous genes from a pre-Ss4R outgroup unexpectedly demonstrate far more instances of neofunctionalization than subfunctionalization. Surprisingly, we find that genes that were retained as duplicates after the teleost-specific whole-genome duplication 320 million years ago were not more likely to be retained after the Ss4R, and that the duplicate retention was not influenced to a great extent by the nature of the predicted protein interactions of the gene products. Finally, we demonstrate that the Atlantic salmon assembly can serve as a reference sequence for the study of other salmonids for a range of purposes.
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IJS, KISLJ, NUK, SBMB, UL, UM, UPUK
Shear stress has an established effect on mature endothelial cells, but less is known about how shear stress regulates endothelial progenitor cells (EPCs). In vitro expanded EPCs isolated from adult ...human blood represent a novel tool in regenerative vessel therapy. However, in vitro culturing may generate cells with unfavourable properties. The aim of the present study was therefore to assess whether shear stress may influence the inflammatory and thrombotic phenotype of in vitro expanded EPCs. In late outgrowth EPCs, 6 hours of shear stress (6.0 dynes/cm2) significantly reduced the mRNA levels of IL-8, COX2, and tissue factor (TF) compared to static controls. This was associated with a reduced TF activity. In contrast, mRNA expression of NOS3 was significantly increased following 6 and 24 hours of shear stress. In accordance with this, NOS3 protein expression was increased following 24 hours of shear stress. Overall stimulation with the proinflammatory mediator, TNFα, for the final 2 hours increased the mRNA expression of IL-6, IL-8, MCP-1, ICAM1, and TF. However exposure to 6 hours of shear stress significantly suppressed the inductory potential of TNFα to increase the mRNA levels of IL-6, IL-8, COX2, and TF. Additionally, TNFα increased TF activity approximately 10 times, an effect that was also significantly reduced by exposure to 6 and 24 hours of shear stress. The effect of shear on the gene levels of TF and NOS3 were not blocked by the NOS inhibitor L-NAME. These observations suggest that EPCs are capable of functionally responding to shear stress.
Oppdateringer av nasjonal traumeplan Gaarder, Christine; Geisner, Thomas; Hermansen, Stig Eggen ...
Tidsskrift for Den norske lægeforening,
2019
Journal Article
Updating the national trauma plan Gaarder, Christine; Geisner, Thomas; Hermansen, Stig Eggen ...
Tidsskrift for den Norske Lægeforening,
2019-Nov-19, 20191119, Volume:
139, Issue:
17
Journal Article
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