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- Circiumaru, A, et al.
(författare)
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SPECIFIC ACPA REACTIVITIES AND INFLAMMATORY BIOMARKERS ALONG WITH ULTRASOUND TENOSYNOVITIS ARE ASSOCIATED WITH ARTHRITIS ONSET IN A POPULATION AT RISK FOR RHEUMATOID ARTHRITIS
- 2020
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 1247-1247
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Anti-citrullinated protein antibodies (ACPA) are characteristic markers for rheumatoid arthritis (RA), developing years before disease onset. Early clinical and biological biomarkers could provide useful information on the onset of RA in predisposed individuals.Objectives:The aim of the study was to investigate whether ACPA along with inflammatory markers and musculoskeletal ultrasound changes could predict arthritis development in individuals at risk for RA.Methods:ACPA-positive individuals with musculoskeletal complaints were referred from primary care to a rheumatology clinic, recruited in the Risk-RA research program and followed-up for up to 3 years, between April 2014 and October 2019. All individuals lacked arthritis both at clinical examination by a trained rheumatologist and ultrasound assessment of hands and feet and any other symptomatic joints (according to EULAR-OMERACT definition). Blood samples were collected at inclusion and were analyzed for 15 ACPA fine specificities (by custom made peptide array), 92 inflammation-associated protein biomarkers (by multiplex immunoassay with Olink extension technology) and HLA-SE (DR low resolution kit). Statistical analysis used univariate and multivariate models with backwards selection and cox regression.Results:268 individuals with a median age of 48 (36-58) were recruited, out of which 212 (79%) were females. 75 (28%) developed arthritis within 11 months of follow-up while the median follow-up for those not developing arthritis was 21 months (14-28). Increased ACPA levels, shorter symptom duration and RF positivity were the main differences between individuals developing arthritis and those who did not. In univariate models, the presence of HLA-SE, specific ACPA reactivities, certain inflammatory markers and ultrasound-detected tenosynovitis were associated with arthritis development. In multivariate analysis the presence of anti-cit-fillagrin (HR 2.1 (95% CI 1.2-3.7, p 0.01), IL6 levels (HR 1.4 (95% CI 1.2-1.7, p 0.0001) and tenosynovitis (HR 2.9 (95% CI 1.7-5.0, p 0.0001) remained significant predictors for arthritis onset.Conclusion:Certain ACPA reactivities together with inflammatory markers and ultrasound-detected tenosynovitis predict arthritis development in predisposed individuals for developing RA.Disclosure of Interests:None declared
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- Kisten, Y, et al.
(författare)
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TENOSYNOVITIS, SYNOVIAL HYPERTROPHY AND FEET BURSITIS ARE USEFUL ULTRASOUND BIOMARKERS FOR PREDICTING ARTHRITIS DEVELOPMENT IN A POPULATION AT-RISK FOR RHEUMATOID ARTHRITIS
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 87-87
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Musculoskeletal ultrasound (MSUS) evaluation of individuals at risk for developing rheumatoid arthritis (RA) having Anti-Citrullinated Protein Antibody (ACPA) positivity and musculoskeletal complaints, may play an important role in the very early detection of RA.Objectives:We aimed to identify which ultrasound markers could predict arthritis development.Methods:Individuals with musculoskeletal complaints with a positive anti-CCP2 test were referred to the rheumatology department for a detailed clinical (68 joint count) and MSUS examination of the hands, feet and any symptomatic joints. Only those without clinical and/or MSUS detected arthritis were included in the RISK RA prospective cohort and followed-up over 3 years/ or until arthritis onset. Using EULAR-OMERACT guidelines1, MSUS markers for synovial hypertrophy (SH) and hyperemia (Doppler activity) were documented for each visit. Finger and wrist tendons were screened for any signs of tenosynovitis (TS), and between metatarsal joints for bursitis. Association of MSUS biomarkers with arthritis development was tested (comparing proportions) using Chi-Squared or Fisher’s exact tests.Results:288 individuals were included from January 2014 to October 2019 (79% female, 35% RF positive, median age 48 years: IQR: 36-58). Within a median of 38 months (IQR: 1-72) since recruitment, 84 individuals (28%) developed an arthritis diagnosis.Prior to obtaining any diagnosis (at inclusion and/or follow-up visit), 95 of the 288 individuals (33%) had at least one type of MSUS anatomical modification present (around the tendons, joint synovium and/or within bursal cavities), and 56% (53/95) of these individuals eventually developed arthritis. Of the remaining 193 that did not present with any obvious MSUS changes, 16% progressed towards arthritis development.The presence of tenosynovitis was detected in 64 of 288 individuals scanned prior to diagnosis and were more frequent in those developing arthritis (44%, 37/84) as compared to those with TS not developing arthritis (13%, 27/204), p<0.0001. The extensor carpi ulnaris wrist tendons were mostly involved. Sonographic changes within the synovium were noted in 11% (32/288) of all individuals, mostly affecting the metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints. There was a higher incidence of synovial hypertrophy detected in those developing arthritis (22%, 18/24), as compared to those that remained arthritis free (7%, 14/204), p<0.0001. The MCP joints with synovial hypertrophy were more prone to arthritis development as compared to the MTP’s. Furthermore, we observed a higher frequency of bursitis between the MTP joints in individuals developing arthritis, as compared to individuals having a bursitis who did not develop arthritis (13%, 11/84 versus 7%, 14/204, p=0.009).Conclusion:Ultrasound biomarkers such as tenosynovitis of the extensor carpi ulnaris, synovial hypertrophy of the MCP joints and feet bursitis have good potential to predict arthritis development in a population at-risk for rheumatoid arthritis.References:[1]Maria-Antonietta D’Agostino et al. RMD Open 2017;3:e 000428Acknowledgements:All study participants and patients, including researchers that are part of the multidisciplinary laboratory, clinical and academic teams of the RISK RA study group, as well as all assisting this research in one form or the other are greatly acknowledged.Disclosure of Interests:None declared
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- Chatzidionysiou, K, et al.
(författare)
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Tocilizumab decreases T cells but not macrophages in the synovium of patients with rheumatoid arthritis while it increases the levels of serum interleukin-6 and RANKL
- 2021
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Ingår i: RMD open. - : BMJ. - 2056-5933. ; 7:2
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Tidskriftsartikel (refereegranskat)abstract
- Our knowledge about the effect of tocilizumab (TCZ) on the synovium in rheumatoid arthritis (RA) is limited. The aim of this study was to investigate the effect of TCZ on citrullination and on inflammation in the synovial tissue and in the peripheral blood.Methods15 patients with RA underwent synovial biopsy before and 8 weeks after TCZ initiation. Clinical evaluation was performed at baseline and at 8 weeks. Using immunohistochemistry, we evaluated the expression of CD68, CD3, CD20, osteoprotegerin (OPG) and receptor activator for nuclear factor-κB ligand (RANKL) before and after treatment with TCZ. We also analysed the expression of protein arginine deiminase (PAD)-2 and PAD-4 enzymes in the synovial tissue and protein citrullination patterns with the help of anticitrullinated protein antibody (ACPA) clones 1325:04C03 and 1325:01B09. Serum levels of interleukin-6 (IL-6), IL-8, RANKL, OPG and C-terminal crosslinked telopeptide type II collagen were measured by ELISA. Paired-wise Wilcoxon signed-rank test was used to compare median values before and after treatment.ResultsDisease activity in patients was reduced from baseline to 8 weeks. Although PAD-2 and PAD-4 expressions remained unchanged after TCZ treatment, the binding of one ACPA clone decreased in the synovial tissue. TCZ did not affect the number of CD68+ macrophages or CD20+ B cells but induced significant decrease in the number of CD3+ T cells. RANKL and OPG expression remained unchanged in the synovial tissue. A significant increase in the levels of IL-6 and RANKL was observed in the serum. This increase was statistically significant in patients who responded to TCZ (achieving Clinical Disease Activity Index low disease activity or remission) but not in non-responders.ConclusionsTCZ reduced synovial T-cell counts but not macrophages. A significant increase of serum IL-6 was observed in responders.
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- Bonow, Johan M., et al.
(författare)
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A multi-disciplinary study of Phanerozoic landscape development in West Greenland
- 2007
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Ingår i: Geological Survey of Denmark and Greenland Bulletin: Review of Survey activities 2006. - 1604-8156. ; :13, s. 33-36
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Tidskriftsartikel (refereegranskat)abstract
- The western margin of the Greenland craton has been muchless stable in the Phanerozoic than previously thought. Thisnew insight has come from close integration of independentdata sets: geomorphological analysis of large-scale landscapes,apatite fission track analysis (AFTA), onshore and offshorestratigraphy and analysis of onshore fault and fracture sys -tems. Each data set records specific and unique parts of theevent chronology and is equally important to establish a con-sistent model. A key area for understanding the Mesozoic-Cenozoic landscape evolution and into the present is theuplifted part of the Nuussuaq Basin, where remnants of pla-nation surfaces cut across the Cretaceous to Eocene sedimen-tary and volcanic rocks. Our integrated analysis concludedthat the West Greenland mountains were formed by lateNeogene tectonic uplift (Fig. 1) and also provided newinsight into early Phanerozoic development. To understandour model, we present the different methods and the resultsthat can be deduced from them.
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| 21. |
- Christerson, Linus, et al.
(författare)
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Typing of Lymphogranuloma Venereum Chlamydia trachomatis Strains
- 2010
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Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 16:11, s. 1777-1779
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Tidskriftsartikel (refereegranskat)abstract
- We analyzed by multilocus sequence typing 77 lymphogranuloma venereum Chlamydia trachomatis strains from men who have sex with men in Europe and the United States. Specimens from an outbreak in 2003 in Europe were monoclonal. In contrast, several strains were in the United States in the 1980s, including a variant from Europe.
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- Møller, Henrik, et al.
(författare)
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Colorectal cancer survival in socioeconomic groups in England : Variation is mainly in the short term after diagnosis
- 2012
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 48:1, s. 46-53
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to examine differences in cancer survival between socioeconomic groups in England, with particular attention to survival in the short term of follow-up. PATIENTS AND METHODS: Individuals diagnosed with colorectal cancer between 1996 and 2004 in England were identified from cancer registry records. Five-year cumulative relative survival and excess death rates were computed. RESULTS: For colon cancer there was a very high excess death rate in the first month of follow-up, and the excess death rate was highest in the socioeconomically deprived groups. In subsequent periods, excess mortality rates were much lower and there was less socioeconomic variation. The pattern of variation in excess death rates was generally similar in rectal cancer but the socioeconomic difference in death rates persisted several years longer. If the excess death rates in the entire colorectal cancer patient population were the same as those observed in the most affluent socioeconomic quintile, the annual reduction would be 360 deaths in colon cancer and 336 deaths in rectal cancer patients. These deaths occurred almost entirely in the first month and the first year after diagnosis. CONCLUSION: Recent developments in the national cancer control agenda have included an increasing emphasis on outcome measures, with short-term cancer survival an operational measure of variation and progress in cancer control. In providing clues to the nature of the survival differences between socioeconomic groups, the results presented here give strong support for this strategy.
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- Turcinov, S, et al.
(författare)
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ULTRASOUND GUIDED BIOPSIES OF RA JOINTS AT TIME OF CLINICAL DIAGNOSIS CONTAIN PROFOUND T CELL CLONALITIES
- 2020
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 1321-1321
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Rheumatoid arthritis (RA) is a disease characterized by synovial joint inflammation, mainly affecting small joints. Histological findings in synovial biopsies ranges from inflammatory infiltration including ectopic lymphoid structures, to a cell sparse fibroid phenotype. T cells in affected joints are non-naïve and have by flow cytometry approaches been shown to have a wide TCR-beta chain gene usage. New technologies allow for analyses of paired TCR sequences and their antigen-specificities.Objectives:To study the alpha/beta-T cell receptor repertoire in single sorted T cells from synovial biopsies at time of RA-diagnosis.Meth ods:Synovial biopsies were taken, primarily using an ultrasound guided technique, from seventeen patients (12 ACPA+, 5 ACPA-) with rheumatoid arthritis. Fresh biopsies were enzymatically digested, followed by mild mechanical treatment, prior to flow cytometry cell sorting. Single cell index sorting of T cells was made into 384-well plates with PCR-buffer followed by a nested PCR and deep sequencing of the TCR amplicons. TCR-receptor sequences showing clonal expansion from four ACPA+ HLA-DRB1*0401 patients were further cloned into SKW3 cells for studies of their reactivity byin vitrostimulation with peptides of viral and citrullinated origin from the literature. A positive response, as measured by CD69-up regulation or IL-2 production, was used to define specificity.Results:Fourteen of the assessed joints were small (1 MTP, 4 MCP and 8 wrists), whereas the remaining three were large joints (2 knees and 1 ankle), table 1. Individual T cells could be isolated from all of these biopsies, with a variating CD4:CD8 ratio. Based on the flow cytometry phenotyping we could identify CD4 T cells of both Treg and T peripheral helper phenotype already at this early time point. Productive alpha/beta-TCR sequences could be retrieved from 16 out of 17 patients and clonal expansion (>1 copy/TCR) was seen in all but one of these patients, with clone sizes ranging between 2 – 34 copies of each TCR.Table 1.Patient characteristics.PatientsGender(F/M)HLA-SE allelesJointsJoint swelling prior to biopsy (months)Stiffness specific joint (median VAS)Pain specific joint (median VAS)ACPA+ (n = 12)9/3*0401, *0404, *0408, *01 and *101 MTP, 4 MCP, 6 wrists, 1 knee4 (1-12)a46 (0-84)45 (22-99)ACPA- (n = 5)3/2*04011 MCP, 2 wrists, 1 ankle, 1 knee5 (0.25-7)59 (15-73)47 (33-81)SKW3 cell lines(patients n = 4)4/0*0401/0404 n=2*0401 n=21 MTP, 3 wrists2 (1-6)50.5 (42-84)50 (40-99)aData not available for one patient. One patient with prior RA-diagnosis, but after 9 months of treatment remission lasting for 20 years.Artificial T cell lines were generated from the expanded clones of HLA-DRB1*04:01 RA subjects. Ourin vitrostimulation protocol identified virus specific CD4 T cells in all samples. So far, no citrulline reactivity has been found. HCMV, followed by HHV were the most commonly found viral reactivities, whereas others were found only in one donor (e.g. JCV, EBV). The majority of clones are thus “orphans”, to which we are still seeking the driving antigen.Conclusion:Clonally expanded T cells are found in the synovium of early RA patients and include virus-specific CD4+ T cells. Our data show that the local T cell repertoire is broad already at the time of RA diagnosisDisclosure of Interests:Sara Turcinov: None declared, Erik af Klint Paid instructor for: Abbvie (courses and lectures), An De Bondt Employee of: Janssen., Muhammad Sohel Mia: None declared, Anca Catrina: None declared, Frederik Stevenaert Employee of: Janssen, Vivianne Malmström Grant/research support from: VM has had research grants from Janssen Pharmaceutica
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- Amour, Maryam A., et al.
(författare)
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Determinants of COVID-19 Vaccine Uptake and Hesitancy among Healthcare Workers in Tanzania : A Mixed-Methods Study
- 2023
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Ingår i: COVID. - : MDPI. - 2673-8112. ; 3:5, s. 777-791
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Tidskriftsartikel (refereegranskat)abstract
- The novel Coronavirus disease 2019 (COVID-19) presents a major threat to public health but can be prevented by safe and effective COVID-19 vaccines. Vaccine acceptance among healthcare workers (HCWs) is essential to promote uptake. This study, aimed to determine the COVID-19 vaccination uptake and hesitancy and its associated factors among HCWs in Tanzania. We employed a convergent-parallel mixed-methods design among 1368 HCWs across health facilities in seven geographical zones in Tanzania in 2021. We collected quantitative data by using an interviewer-administered questionnaire and qualitative data, using in-depth interviews and focus group discussions. Participants in the quantitative aspect were conveniently selected whereas those in the qualitative aspect were purposively selected based on their role in patient care, management, and vaccine provision. Stata software version 16.1 was used in the analysis of quantitative data and thematic analysis for the qualitative data. Multiple logistic regression was used to assess the determinants of COVID-19 vaccine uptake. The median age of 1368 HCWs was 33, and the interquartile range was 28-43 years; 65.6% were aged 30+ years, and 60.1% were females. Over half (53.4%) of all HCWs received the COVID-19 vaccine, 33.6% completely refused, and 13% chose to wait. HCWs aged 40+ years, from lower-level facilities (district hospitals and health centers), who worked 6+ years, and with perceived high/very high risk of COVID-19 infection had significantly higher odds of vaccine uptake. The qualitative data revealed misinformation and inadequate knowledge about COVID-19 vaccine safety and efficacy as the key barriers to uptake. Nearly half of all HCWs in Tanzania are still unvaccinated against COVID-19. The predominance of contextual influence on COVID-19 vaccine uptake calls for interventions to focus on addressing contextual determinants, focusing on younger HCWs' population, short working duration, those working at different facility levels, and providing adequate vaccine knowledge.
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| 44. |
- Basten, B., et al.
(författare)
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Modular language implementation in Rascal - experience report
- 2015
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Ingår i: Science of Computer Programming. - : Elsevier BV. - 0167-6423. ; 114, s. 7-19
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Tidskriftsartikel (refereegranskat)abstract
- All software evolves, and programming languages and programming language tools are no exception. And just like in ordinary software construction, modular implementations can help ease the process of changing a language implementation and its dependent tools. However, the syntactic and semantic dependencies between language features make this a challenging problem. In this paper we detail how programming languages can be implemented in a modular fashion using the RASCAL meta-programming language. RASCAL supports extensible definition of concrete syntax, abstract syntax and operations on concrete and abstract syntax trees like matching, traversal and transformation. As a result, new language features can be added without having to change existing code. As a case study, we detail our solution of the LDTA'11 Tool Challenge: a modular implementation of OBERON-0, a relatively simple imperative programming language. The approach we sketch can be applied equally well to the implementation of domain-specific languages.
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| 45. |
- Boeth, Heide, et al.
(författare)
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Association between changes in molecular biomarkers of cartilage matrix turnover and changes in knee articular cartilage : a longitudinal pilot study
- 2019
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Ingår i: Journal of Experimental Orthopaedics. - : Springer Science and Business Media LLC. - 2197-1153. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: An early detection of Osteoarthritis is urgently needed and still not possible until today. The aim of the study was to assess whether molecular biomarkers of cartilage turnover are associated with longitudinal change in knee cartilage thickness during a 2 year period in individuals with increased risk of developing knee osteoarthritis. A secondary aim was to assess whether prior knee injury or subjective patient-reported outcomes at baseline (BL) were associated with articular cartilage changes. Nineteen volleyball players (mean age 46.5 ± 4.9 years, 47% male) with a 30-year history of regular high impact training were recruited. The serum biomarkers Cpropeptide of type II procollagen (CPII), cartilage oligomeric matrix protein (COMP), collagenase generated carboxy-terminal neoepitope of type II collagen (sC2C), cartilage intermediate layer protein 2 (CILP-2), and the urine biomarkers C-telopeptide of type II collagen (CTX-II) and collagenase-generated peptide(s) of type II collagen (C2C-HUSA) were assessed at BL and at 2 year follow up (FU). Femorotibial cartilage thinning, thickening and absolute thickness change between BL and FU was evaluated from magnetic resonance imaging. Subjective clinical status at BL was evaluated by the International Knee Documentation Committee Subjective Knee Form and the Short-Form 36 Physical Component Score. Results: CILP-2 was significantly higher at FU and linearly associated with the absolute cartilage thickness change during the experimental period. Prior injury was a predictor of increased absolute cartilage thickness change. Conclusion: Measuring the change in the cartilage biomarker CILP-2 might be a valid and sensitive method to detect early development of knee osteoarthritis as CILP-2 appears to be related to cartilage thickness loss in certain individuals with increased risk of developing knee osteoarthritis. Prior knee injury may be predictive of increased articular cartilage thickness change.
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