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- Tscherne, A, et al.
(author)
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Adaptation of Brucella melitensis Antimicrobial Susceptibility Testing to the ISO 20776 Standard and Validation of the Method
- 2022
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In: Microorganisms. - : MDPI AG. - 2076-2607. ; 10:7
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Journal article (peer-reviewed)abstract
- Brucellosis, mainly caused by Brucella (B.) melitensis, is associated with a risk of chronification and relapses. Antimicrobial susceptibility testing (AST) standards for B. melitensis are not available, and the agent is not yet listed in the EUCAST breakpoint tables. CLSI recommendations for B. melitensis exist, but they do not fulfill the requirements of the ISO 20776 standard regarding the culture medium and the incubation conditions. Under the third EU Health Programme, laboratories specializing in the diagnostics of highly pathogenic bacteria in their respective countries formed a working group within a Joint Action aiming to develop a suitable method for the AST of B. melitensis. Under the supervision of EUCAST representatives, this working group adapted the CLSI M45 document to the ISO 20776 standard after testing and validation. These adaptations included the comparison of various culture media, culture conditions and AST methods. A Standard Operation Procedure was derived and an interlaboratory validation was performed in order to evaluate the method. The results showed pros and cons for both of the two methods but also indicate that it is not necessary to abandon Mueller–Hinton without additives for the AST of B. melitensis.
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- Holmqvist, Marie E., et al.
(author)
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Risk of Venous Thromboembolism in Patients With Rheumatoid Arthritis and Association With Disease Duration and Hospitalization
- 2012
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In: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 308:13, s. 1350-1356
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Journal article (peer-reviewed)abstract
- Context Recent reports suggest that rheumatoid arthritis (RA) may be a risk factor for venous thromboembolism (VTE), particularly in conjunction with hospitalization. Using hospitalization data to identify RA and VTE may identify patients when they are at elevated risk for other reasons, obscuring the incompletely understood underlying association between RA and VTE and leading to inappropriate institution or timing of interventions. Objective To estimate risks for VTE in patients with RA, including the relation of these risks to disease duration and hospitalization. Design, Setting, and Patients Prospective, population-based cohort study of 1 prevalent RA cohort (n = 37 856), 1 incident RA cohort (n = 7904), and matched general population comparison cohorts, all from Sweden, with follow-up from 1997 through 2010. Main Outcome Measure First-time VTE. Results Patients with prevalent RA were at greater risk of VTE than the general population (rate, 5.9 [95% CI, 5.1-6.6] vs 2.8 [95% CI, 2.6-3.1] per 1000 person-years (adjusted hazard ratio [HR], 2.0 [95% CI, 1.9-2.2]; P < .001). By the time of RA symptom onset, there was no statistically significant association between a history of VTE and RA (odds ratio, 1.2 [95% CI, 1.0-1.4]; P = .08; 150 events in the RA cohort vs 587 in the comparison cohort). Counting from RA diagnosis, an increased rate in the RA cohort vs the comparison cohort (3.8 [95% CI, 2.5-5.2] vs 2.4 [95% CI, 1.9-2.9] per 1000 person-years; HR, 1.6 [95% CI, 1.1-2.5]; P = .02) was detected within the first year and did not increase further during the first decade. Although rates for VTE following hospitalization were higher, the 1-year rate of VTE per 1000 person-years was not higher in the RA cohort than in the comparison cohort after hospital discharge (11.8 [95% CI, 8.6-15.1] vs 13.1 [11.3-14.8]; HR, 1.0 [95% CI, 0.7-1.4]; P = .90). The rates of VTE increased with age but were largely similar across sex and rheumatoid factor status, as were the HRs for VTE across age, sex, and rheumatoid factor status. Conclusions Compared with the general population, Swedish patients with RA had an elevated risk for VTE that was stable over the first 10 years after diagnosis. Although hospitalization was a risk factor for VTE the first year after discharge, the excess risk was not greater in patients with RA than in the general population.
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- Mantel, H. T. J., et al.
(author)
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Strict Selection Alone of Patients Undergoing Liver Transplantation for Hilar Cholangiocarcinoma Is Associated with Improved Survival
- 2016
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:6
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Journal article (peer-reviewed)abstract
- Liver transplantation for hilar cholangiocarcinoma (hCCA) has regained attention since the Mayo Clinic reported their favorable results with the use of a neo-adjuvant chemoradiation protocol. However, debate remains whether the success of the protocol should be attributed to the neo-adjuvant therapy or to the strict selection criteria that are being applied. The aim of this study was to investigate the value of patient selection alone on the outcome of liver transplantation for hCCA. In this retrospective study, patients that were transplanted for hCCA between 1990 and 2010 in Europe were identified using the European Liver Transplant Registry (ELTR). Twenty-one centers reported 173 patients (69%) of a total of 249 patients in the ELTR. Twenty-six patients were wrongly coded, resulting in a study group of 147 patients. We identified 28 patients (19%) who met the strict selection criteria of the Mayo Clinic protocol, but had not undergone neo-adjuvant chemoradiation therapy. Five-year survival in this subgroup was 59%, which is comparable to patients with pretreatment pathological confirmed hCCA that were transplanted after completion of the chemoradiation protocol at the Mayo Clinic. In conclusion, although the results should be cautiously interpreted, this study suggests that with strict selection alone, improved survival after transplantation can be achieved, approaching the Mayo Clinic experience.
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- Muller, I, et al.
(author)
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IDENTIFICATION OF DIFFERENTIALLY EXPRESSED GENES IN EARLY RHEUMATOID ARTHRITIS PATIENTS RESPONDING TO TOCILIZUMAB
- 2021
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In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 12-12
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Conference paper (other academic/artistic)abstract
- Tocilizumab (TCZ) is a monoclonal antibody that binds to the interleukin 6 receptor (IL-6R), inhibiting IL-6R signal transduction to downstream inflammatory mediators. TCZ has shown to be effective as monotherapy in early rheumatoid arthritis (RA) patients (1). However, approximately one third of patients inadequately respond to therapy and the biological mechanisms underlying lack of efficacy for TCZ remain elusive (1). Here we report gene expression differences, in both whole blood and peripheral blood mononuclear cells (PBMC) RNA samples between early RA patients, categorized by clinical TCZ response (reaching DAS28 < 3.2 at 6 months). These findings could lead to identification of predictive biomarkers for TCZ response and improve RA treatment strategies.Objectives:To identify potential baseline gene expression markers for TCZ response in early RA patients using an RNA-sequencing approach.Methods:Two cohorts of RA patients were included and blood was collected at baseline, before initiating TCZ treatment (8 mg/kg every 4 weeks, intravenously). DAS28-ESR scores were calculated at baseline and clinical response to TCZ was defined as DAS28 < 3.2 at 6 months of treatment. In the first cohort (n=21 patients, previously treated with DMARDs), RNA-sequencing (RNA-seq) was performed on baseline whole blood PAXgene RNA (Illumina TruSeq mRNA Stranded) and differential gene expression (DGE) profiles were measured between responders (n=14) and non-responders (n=7). For external replication, in a second cohort (n=95 therapy-naïve patients receiving TCZ monotherapy), RNA-seq was conducted on baseline PBMC RNA (SMARTer Stranded Total RNA-Seq Kit, Takara Bio) from the 2-year, multicenter, double-blind, placebo-controlled, randomized U-Act-Early trial (ClinicalTrials.gov identifier: NCT01034137) and DGE was analyzed between 84 responders and 11 non-responders.Results:Whole blood DGE analysis showed two significantly higher expressed genes in TCZ non-responders (False Discovery Rate, FDR < 0.05): urotensin 2 (UTS2) and caveolin-1 (CAV1). Subsequent analysis of U-Act-Early PBMC DGE showed nine differentially expressed genes (FDR < 0.05) of which expression in clinical TCZ non-responders was significantly higher for eight genes (MTCOP12, ZNF774, UTS2, SLC4A1, FECH, IFIT1B, AHSP, and SPTB) and significantly lower for one gene (TND2P28M). Both analyses were corrected for baseline DAS28-ESR, age and gender. Expression of UTS2, with a proposed function in regulatory T-cells (2), was significantly higher in TCZ non-responders in both cohorts. Furthermore, gene ontology enrichment analysis revealed no distinct gene ontology or IL-6 related pathway(s) that were significantly different between TCZ-responders and non-responders.Conclusion:Several genes are differentially expressed at baseline between responders and non-responders to TCZ therapy at 6 months. Most notably, UTS2 expression is significantly higher in TCZ non-responders in both whole blood as well as PBMC cohorts. UTS2 could be a promising target for further analyses as a potential predictive biomarker for TCZ response in RA patients in combination with clinical parameters (3).References:[1]Bijlsma JWJ, Welsing PMJ, Woodworth TG, et al. Early rheumatoid arthritis treated with tocilizumab, methotrexate, or their combination (U-Act-Early): a multicentre, randomised, double-blind, double-dummy, strategy trial. Lancet. 2016;388(10042):343-55.[2]Bhairavabhotla R, Kim YC, Glass DD, et al. Transcriptome profiling of human FoxP3+ regulatory T cells. Human Immunology. 2016;77(2):201-13.[3]Gosselt HR, Verhoeven MMA, Bulatovic-Calasan M, et al. Complex machine-learning algorithms and multivariable logistic regression on par in the prediction of insufficient clinical response to methotrexate in rheumatoid arthritis. Journal of Personalized Medicine. 2021;11(1).Disclosure of Interests:None declared
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