| 1. |
- Hamfjord, J., et al.
(författare)
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Total circulating cell-free DNA as a prognostic biomarker in metastatic colorectal cancer before first-line oxaliplatin-based chemotherapy
- 2019
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Ingår i: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 30:7, s. 1088-1095
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Tidskriftsartikel (refereegranskat)abstract
- Background Metastatic colorectal cancer (mCRC) is a heterogeneous disease where prognosis is dependent both on tumor biology and host factors. Total circulating cell-free DNA (cfDNA) has shown to harbor prognostic information in mCRC, although less is known about the biological correlates of cfDNA levels in this patient group. The primary objective was to evaluate the prognostic value of pretreatment cfDNA in patients receiving the first-line oxaliplatin-based chemotherapy for mCRC, by using a predefined upper limit of normal (ULN) from a cohort of presumed healthy individuals. The secondary objective was to model cfDNA levels as a function of predefined tumor and host factors. Patients and methods This was a retrospective post hoc study based on a prospective multicenter phase III trial, the NORDIC-VII study. DNA was purified from 547 plasma samples and cfDNA quantified by a droplet digital PCR assay (B2M, PPIA) with controls for lymphocyte contamination. Main clinical end point was overall survival (OS). Results cfDNA was quantified in 493 patients, 54 were excluded mainly due to lymphocyte contamination. Median cfDNA level was 7673 alleles/ml (1050-1645000) for B2M and 5959 alleles/ml (555-854167) for PPIA. High cfDNA levels were associated with impaired outcome; median OS of 16.6months for levels above ULN and 25.9months for levels below ULN (hazard ratio = 1.83, 95% confidence interval 1.51-2.21, P<0.001). The result was confirmed in multivariate OS analysis adjusting for established clinicopathological characteristics. A linear regression model predicted cfDNA levels from sum of longest tumor diameters by RECIST, the presence of liver metastases and systemic inflammatory response as measured by interleukin 6 (F(6, 357) = 62.7, P<0.001). Conclusion cfDNA holds promise as a minimally invasive and clinically relevant prognostic biomarker in mCRC before initiating first-line oxaliplatin-based chemotherapy and may be a complex entity associated with tumor burden, liver metastases and systemic inflammatory response. Trial registration ClinicalTrials.gov, NCT00145314.
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| 4. |
- Roselli, Carolina, et al.
(författare)
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Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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| 5. |
- Duvetorp, Albert, et al.
(författare)
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Quality of life and contact with healthcare systems among patients with psoriasis and psoriatic arthritis: results from the NORdic PAtient survey of Psoriasis and Psoriatic arthritis (NORPAPP)
- 2019
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Ingår i: Archives of Dermatological Research. - : SPRINGER. - 0340-3696 .- 1432-069X. ; 311:5, s. 351-360
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasis (skin psoriasis, PsO) is a chronic inflammatory condition. In about one-third of cases, the joints are affected (psoriatic arthritis, PsA). Both conditions, especially PsA, profoundly impact patients health-related quality of life (HRQoL). To describe the impact of psoriasis on HRQoL and patients contact with the healthcare system in Sweden, Denmark, and Norway, the NORdic PAtient survey of Psoriasis and Psoriatic arthritis (NORPAPP) asked 22,050 adults randomly selected in Sweden, Denmark and Norway if they had psoriasis. 1264 individuals who reported physician-diagnosed PsO/PsA were invited to the full survey; 1221 responded (74.6% diagnosed with PsO alone; 25.4% with PsA +/- PsO). Respondents with PsA most frequently consulted a rheumatologist; however, 14.3% had never seen a rheumatologist. Respondents with PsO alone most frequently consulted a general practitioner and 10.7% had never seen a dermatologist (although those with severe symptoms visited dermatologists more often). Negative impacts on HRQoL were reported by 38.1% of respondents with PsO [mostly limitations on clothing (22.6%), sleep disorders (16%), and depression/anxiety (16%)] and by 73% of respondents with PsA [mostly limitations on clothing (41.8%), sports/leisure (44.0%), or daily routine (45.1%) and sleeping disorders]. Absence from work/education was more common with PsA +/- PsO (51.9%) than PsO alone (15.1%). In this survey in Sweden, Denmark, and Norway, the impact of psoriasis on the respondents HRQoL was profound and was greater for PsA than for PsO, as was sickness absence. Sleeping disorders and depression were common and should not be overlooked.
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| 6. |
- Tarpgaard, Line S., et al.
(författare)
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Intact and cleaved plasma soluble urokinase receptor in patients with metastatic colorectal cancer treated with oxaliplatin with or without cetuximab
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 137:10, s. 2470-2477
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Tidskriftsartikel (refereegranskat)abstract
- Circulating forms of the urokinase plasminogen activator receptor (uPAR) are associated with prognosis in patients with colorectal cancer. Preclinical studies have shown that uPAR can influence the state of phosphorylation and signalling activity of the epidermal growth factor receptor (EGFR) in a ligand-independent manner. The purpose of the study was to evaluate whether plasma soluble intact and cleaved uPAR(I-III) + (II-III) levels could identify a subpopulation of patients with metastatic colorectal cancer (mCRC) where treatment with cetuximab would have a beneficial effect. Plasma samples were available from 453 patients treated in the NORDIC VII study. Patients were randomized between FLOX and FLOX + cetuximab. The levels of uPAR(I-III) 1(II-III) were determined by time-resolved fluorescence immunoassay. We demonstrated that higher baseline plasma uPAR(I-III) 1(II-III) levels were significantly associated with shorter progression-free survival (PFS) (HR51.30, 1.14-1.48, p=0.0001) and overall survival (OS) (HR51.75, 1.52-2.02, p < 0.0001). Multivariate Cox analysis showed that plasma uPAR(I-III) 1(II-III) was an independent biomarker of short OS (HR51.45, 1.20-1.75, p=0.0001). There were no significant interactions between plasma uPAR(I-III) 1(II-III) levels, KRAS mutational status and treatment either PFS (p=0.43) or OS (p=0.095). However, further explorative analyses indicated that patients with low levels of circulating suPAR and a KRAS wild-type tumor have improved effect from treatment with FLOX+cetuximab as compared to patients with KRAS wild-type and high levels of suPAR. These results thus support the preclinical findings and should be further tested in an independent clinical data set.
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| 7. |
- Tveit, K. S., et al.
(författare)
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Treatment use and satisfaction among patients with psoriasis and psoriatic arthritis: results from the NORdic PAtient survey of Psoriasis and Psoriatic arthritis (NORPAPP)
- 2019
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Ingår i: Journal of the European Academy of Dermatology and Venereology. - : WILEY. - 0926-9959 .- 1468-3083. ; 33:2, s. 340-354
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Tidskriftsartikel (refereegranskat)abstract
- Background There are scarce data in Scandinavia about treatment satisfaction among patients with psoriasis (PsO) and/or psoriatic arthritis (PsA). The number of patients receiving systemic treatment is unknown. Objective To describe patients experience of treatments for PsO/PsA in Sweden, Denmark and Norway, addressing communication with physicians, satisfaction with treatment and concerns regarding treatment options. Methods The NORdic PAtient survey of Psoriasis and Psoriatic arthritis (NORPAPP) asked 22 050 adults (randomly selected from the YouGov panels in Sweden, Denmark and Norway) whether they had PsO/PsA. A total of 1264 individuals who reported physician-diagnosed PsO/PsA were invited to participate in the full survey; 96.6% responded positively. Results Systemic treatment use was reported by 14.6% (biologic: 8.1%) of respondents with PsO only and by 58.5% (biologic: 31.8%) of respondents with PsA. Biologic treatments were more frequently reported by respondents considering their disease severe (26.8% vs 6.7% non-severe) and those who were members of patient organizations (40.7% vs 6.9% non-members). Discussing systemic treatments with their physician was reported significantly more frequently by respondents with PsA, those perceiving their disease as severe (although 35.2% had never discussed systemic treatment with their physician) and those reporting being a member of a patient organization (P amp;lt; 0.05). Many respondents reported health risk concerns and dissatisfaction with their treatment. Of special interest was that respondents aged 45-75 years reported less experience with biologics (8.1%) than those aged 18-44 years (21.5%). The older respondents also reported more uncertainty regarding long-term health risks related to systemic treatments (most [66.7-72.9%] responded do not know when asked about the risk of systemic options). Conclusion It appears likely that substantial numbers of Scandinavians suffering from severe PsO/PsA are not receiving optimal treatment from a patient perspective, particularly older patients. Also, one-third of respondents with severe symptoms had never discussed systemic treatment with a physician.
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| 8. |
- Buttazzoni, Christian, et al.
(författare)
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Does a childhood fracture predict low bone mass in young adulthood? - A 27-year prospective controlled study.
- 2013
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 28:2, s. 351-359
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A fracture in childhood is associated with low bone mineral density (BMD), but it is debated whether a fracture at growth also predicts low BMD in young adulthood. PURPOSE: To gender-specifically evaluate whether children with a fracture are at increased risk of low BMD in young adulthood. METHODS: Distal forearm BMD (g/cm(2) ) was measured with single photon absorptiometry (SPA) in 47 boys and 26 girls (mean age 10 years, range 3-16) with an index fracture and in 41 boys and 43 girls (mean age 10 years, range 4-16) with no fracture. BMD was re-measured mean 27 years later with the same SPA apparatus and with dual energy absorptiometry (DXA), quantitative ultrasound (QUS) and peripheral computed tomography (pQCT). Individual Z-scores were calculated using the control cohort as reference population. Data are presented as means with 95% confidence intervals (95% CI) within brackets and correlation with Pearson's correlation coefficient RESULTS: Boys with an index fracture had at fracture event a distal forearm BMD Z-score of -0.4 (-0.7, -0.1) and at follow-up -0.4 (-0.7, -0.1). Corresponding values in girls were -0.2 (-0.5, 0.1) and -0.3 (-0.7, 0.1). The deficit in absolute bone mass was driven by men with index fractures in childhood due to low rather than moderate or high energy. There were no changes in BMD Z-score during the follow-up period. The BMD deficit at follow-up was in boys with an index fracture verified with all advocated techniques CONCLUSIONS: A childhood fracture in men was associated with low BMD and smaller bone size in young adulthood while the deficit in women did not reach statistical significance. © 2012 American Society for Bone and Mineral Research.
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| 9. |
- Dueland, Svein, et al.
(författare)
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Chemotherapy or Liver Transplantation for Nonresectable Liver Metastases From Colorectal Cancer?
- 2015
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Ingår i: Annals of Surgery. - 0003-4932 .- 1528-1140. ; 261:5, s. 956-960
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The primary objective was to compare overall survival (OS) in patients with colorectal cancer (CRC) with nonresectable liver-only metastases treated by liver transplantation or chemotherapy. Background: CRC is the third most common cancer worldwide. About 50% of patients will develop metastatic disease primarily to the liver and the lung. The majority of patients with liver metastases receive palliative chemotherapy, with a median OS of trial patients of about 2 years, and less than 10% are alive at 5 years. Methods: Patients with nonresectable liver-only CRC metastases underwent liver transplantation in the SECA study (n = 21). Disease-free survival (DFS) and OS of patients included in the SECA study were compared with progression-free survival (PFS) and OS in a similar cohort of CRC patients with liver-only disease included in a first-line chemotherapy study, the NORDIC VII study (n = 47). PFS/DFS and OS were estimated by the Kaplan-Meier method. Results: DFS/PFS in both groups were 8 to 10 months. However, a dramatic difference in OS was observed. The 5-year OS rate was 56% in patients undergoing liver transplantation compared with 9% in patients starting first-line chemotherapy. The reason for the large difference in OS despite similar DFS/PFS is likely different metastatic patterns at relapse/progression. Relapse in the liver transplantation group was often detected as small, slowly growing lung metastases, whereas progression of nonresectable liver metastases was observed in the chemotherapy group. Conclusions: Compared with chemotherapy, liver transplantation resulted in a marked increased OS in CRC patients with nonresectable liver-only metastases.
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| 10. |
- Freedman, Ben, et al.
(författare)
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Screening for Atrial Fibrillation A Report of the AF-SCREEN International Collaboration
- 2017
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Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 135:19, s. 1851-
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed in September 2015 to promote discussion and research about AF screening as a strategy to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs. During 2016, 60 expert members of AF-SCREEN, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare sections of a draft document. In August 2016, 51 members met in Rome to discuss the draft document and consider the key points arising from it using a Delphi process. These key points emphasize that screen-detected AF found at a single timepoint or by intermittent ECG recordings over 2 weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. With regard to the methods of mass screening, handheld ECG devices have the advantage of providing a verifiable ECG trace that guidelines require for AF diagnosis and would therefore be preferred as screening tools. Certain patient groups, such as those with recent embolic stroke of uncertain source (ESUS), require more intensive monitoring for AF. Settings for screening include various venues in both the community and the clinic, but they must be linked to a pathway for appropriate diagnosis and management for screening to be effective. It is recognized that health resources vary widely between countries and health systems, so the setting for AF screening should be both country-and health system-specific. Based on current knowledge, this white paper provides a strong case for AF screening now while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.
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