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| 2. |
- Bombarda, F., et al.
(author)
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Runaway electron beam control
- 2019
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In: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
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Journal article (peer-reviewed)
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| 3. |
- Aamodt, K., et al.
(author)
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The ALICE experiment at the CERN LHC
- 2008
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In: Journal of Instrumentation. - 1748-0221. ; 3:S08002
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Research review (peer-reviewed)abstract
- ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries, Its overall dimensions are 16 x 16 x 26 m(3) with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008.
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| 4. |
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- 2018
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:1
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Research review (peer-reviewed)
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| 5. |
- Krasilnikov, A., et al.
(author)
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Evidence of 9 Be + p nuclear reactions during 2ω CH and hydrogen minority ICRH in JET-ILW hydrogen and deuterium plasmas
- 2018
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:2
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Journal article (peer-reviewed)abstract
- The intensity of 9Be + p nuclear fusion reactions was experimentally studied during second harmonic (2ω CH) ion-cyclotron resonance heating (ICRH) and further analyzed during fundamental hydrogen minority ICRH of JET-ILW hydrogen and deuterium plasmas. In relatively low-density plasmas with a high ICRH power, a population of fast H+ ions was created and measured by neutral particle analyzers. Primary and secondary nuclear reaction products, due to 9Be + p interaction, were observed with fast ion loss detectors, γ-ray spectrometers and neutron flux monitors and spectrometers. The possibility of using 9Be(p, d)2α and 9Be(p, α)6Li nuclear reactions to create a population of fast alpha particles and study their behaviour in non-active stage of ITER operation is discussed in the paper.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
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Overview of the JET results
- 2015
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In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 55:10
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Journal article (peer-reviewed)
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| 12. |
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| 28. |
- Adcox, K, et al.
(author)
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PHENIX detector overview
- 2003
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In: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - 0167-5087. ; 499:2-3, s. 469-479
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Journal article (peer-reviewed)abstract
- The PHENIX detector is designed to perform a broad study of A-A, p-A, and p-p collisions to investigate nuclear matter under extreme conditions. A wide variety of probes, sensitive to all timescales, are used to study systematic variations with species and energy as well as to measure the spin structure of the nucleon. Designing for the needs of the heavy-ion and polarized-proton programs has produced a detector with unparalleled capabilities. PHENIX measures electron and muon pairs, photons, and hadrons with excellent energy and momentum resolution. The detector consists of a large number of subsystems that are discussed in other papers in this volume. The overall design parameters of the detector are presented. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 29. |
- Jones, Gregory T., et al.
(author)
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Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci
- 2017
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In: Circulation Research. - 0009-7330 .- 1524-4571. ; 120:2, s. 341-
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Journal article (peer-reviewed)abstract
- Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
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| 30. |
- Helgadottir, Anna, et al.
(author)
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The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm
- 2008
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:2, s. 217-224
-
Journal article (peer-reviewed)abstract
- Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD)(1-4) and type 2 diabetes (T2D)(5-7), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.
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| 31. |
- Claassen, Y. H. M., et al.
(author)
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International comparison of treatment strategy and survival in metastatic gastric cancer
- 2019
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In: BJS Open. - : JOHN WILEY & SONS LTD. - 2474-9842. ; 3:1, s. 56-61
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Journal article (peer-reviewed)abstract
- BackgroundIn the randomized Asian REGATTA trial, no survival benefit was shown for additional gastrectomy over chemotherapy alone in patients with advanced gastric cancer with a single incurable factor, thereby discouraging surgery for these patients. The purpose of this study was to evaluate treatment strategies for patients with metastatic gastric cancer in daily practice in five European countries, along with relative survival in each country. MethodsNationwide population-based data from Belgium, Denmark, the Netherlands, Norway and Sweden were combined. Patients with primary metastatic gastric cancer diagnosed between 2006 and 2014 were included. The proportion of gastric resections performed and the administration of chemotherapy (irrespective of surgery) within each country were determined. Relative survival according to country was calculated. ResultsOverall, 15 057 patients with gastric cancer were included. The proportion of gastric resections varied from 81 per cent in the Netherlands and Denmark to 183 per cent in Belgium. Administration of chemotherapy was 392 per cent in the Netherlands, compared with 632 per cent in Belgium. The 6-month relative survival rate was between 390 (95 per cent c.i. 378 to 402) per cent in the Netherlands and 541 (521 to 569) per cent in Belgium. ConclusionThere is variation in the use of gastrectomy and chemotherapy in patients with metastatic gastric cancer, and subsequent differences in survival.
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| 32. |
- Claassen, Y. H.M., et al.
(author)
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North European comparison of treatment strategy and survival in older patients with resectable gastric cancer : A EURECCA upper gastrointestinal group analysis
- 2018
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In: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983. ; 44:12, s. 1982-1989
-
Journal article (peer-reviewed)abstract
- Background: As older gastric cancer patients are often excluded from randomized clinical trials, the most appropriate treatment strategy for these patients remains unclear. The current study aimed to gain more insight in treatment strategies and relative survival of older patients with resectable gastric cancer across Europe. Methods: Population-based cohorts from Belgium, Denmark, The Netherlands, Norway, and Sweden were combined. Patients ≥70 years with resectable gastric cancer (cT1-4a, cN0-2, cM0), diagnosed between 2004 and 2014 were included. Resection rates, administration of chemotherapy (irrespective of surgery), and relative survival within a country according to stage were determined. Results: Overall, 6698 patients were included. The percentage of operated patients was highest in Belgium and lowest in Sweden for both stage II (74% versus 56%) and stage III disease (57% versus 25%). For stage III, chemotherapy administration was highest in Belgium (44%) and lowest in Sweden (2%). Three year relative survival for stage I, II, and III disease in Belgium was 67.8% (95% CI:62.8–72.6), 41.2% (95% CI:37.3–45.2), 17.8% (95% CI:12.5–24.0), compared with 56.7% (95% CI:51.5–61.7), 31.3% (95% CI:27.6–35.2), 8.2% (95% CI:4.4–13.4) in Sweden. There were no significant differences in treatment strategies of patients with stage I disease. Conclusion: Substantial treatment differences are observed across North European countries for patients with stages II and III resectable gastric cancer aged 70 years or older. In the present comparison, treatment strategies with a higher proportion of patients undergoing surgery seemed to be associated with higher survival rates for patients with stages II or III disease.
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| 33. |
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| 34. |
- Li, Chen, et al.
(author)
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Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length
- 2020
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In: American Journal of Human Genetics. - : CELL PRESS. - 0002-9297 .- 1537-6605. ; 106:3, s. 389-404
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Journal article (peer-reviewed)abstract
- Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
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| 35. |
- Brunkwall, J., et al.
(author)
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Endovascular Repair of Acute Uncomplicated Aortic Type B Dissection Promotes Aortic Remodelling: 1 Year Results of the ADSORB Trial
- 2014
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In: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1532-2165 .- 1078-5884. ; 48:3, s. 285-291
-
Journal article (peer-reviewed)abstract
- Objectives: Uncomplicated acute type B aortic dissection (AD) treated conservatively has a 10% 30-day mortality and up to 25% need intervention within 4 years. In complicated AD, stent grafts have been encouraging. The aim of the present prospective randomised trial was to compare best medical treatment (BMT) with BMT and Gore TAG stent graft in patients with uncomplicated AD. The primary endpoint was a combination of incomplete/no false lumen thrombosis, aortic dilatation, or aortic rupture at 1 year. Methods: The AD history had to be less than 14 days, and exclusion criteria were rupture, impending rupture, malperfusion. Of the 61 patients randomised, 80% were DeBakey type IIIB. Results: Thirty-one patients were randomised to the BMT group and 30 to the BMT+TAG group. Mean age was 63 years for both groups. The left subclavian artery was completely covered in 47% and in part in 17% of the cases. During the first 30 days, no deaths occurred in either group, but there were three crossovers from the BMT to the BMT TAG group, all due to progression of disease within 1 week. There were two withdrawals from the BMT+TAG group. At the 1-year follow up there had been another two failures in the BMT group: one malperfusion and one aneurysm formation (p = .056 for all). One death occurred in the BMT TAG group. For the overall endpoint BMT+TAG was significantly different from BMT only (p < .001). Incomplete false lumen thrombosis, was found in 13 (43%) of the TAG+BMT group and 30 (97%) of the BMT group (p < .001). The false lumen reduced in size in the BMT+TAG group (p < .001) whereas in the BMT group it increased. The true lumen increased in the BMT TAG (p < .001) whereas in the BMT group it remained unchanged. The overall transverse diameter was the same at the beginning and after 1 year in the BMT group (42.1 mm), but in the BMT+TAG it decreased (38.8 mm; p = .062). Conclusions: Uncomplicated AD can be safely treated with the Gore TAG device. Remodelling with thrombosis of the false lumen and reduction of its diameter is induced by the stent graft, but long term results are needed. (C) 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
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| 36. |
- Huang, L, et al.
(author)
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Largely varying patterns and trends of primary cancer-directed resection for gastric carcinoma with synchronous distant metastasis in Europe and the US: a population-based study calling for further standardization of care
- 2021
-
In: Therapeutic advances in medical oncology. - : SAGE Publications. - 1758-8340 .- 1758-8359. ; 13, s. 17588359211027837-
-
Journal article (peer-reviewed)abstract
- The role of resection remains debated in cases of metastatic gastric carcinoma (mGC). Some mGCs are technically resectable. At the population level, the real-world application of resection for mGC remains largely unclear in most Western countries. This large, population-based international investigation aimed to reveal the resection patterns and trends for mGC and the treatment-associated factors in Europe and the US. Methods: Data on cases with microscopically-confirmed primary invasive stomach carcinoma with distant metastasis were obtained from the nationwide cancer registries of the Netherlands, Belgium, Norway, Sweden, Estonia, and Slovenia and the US Surveillance, Epidemiology, and End Results-18 database. We calculated age-standardized rates of primary cancer-directed resection and assessed resection trends using linear regression. We investigated associations of treatment with patient and cancer factors using multivariable-adjusted log-binomial regression. Results: Among 133,321 patients with gastric cancer, overall, 40,215 cases with mGC diagnosed between 2003–2017 were investigated. Age-standardized resection rates significantly declined over time in the US, Belgium, Sweden, and Norway (by 5–14%). Resection rates greatly differed from 5% to 16% in 2013–2014. Cases with older ages, cardia tumors, or tumors involving adjacent structures were significantly less often operated across most countries. Sex was not significantly associated with resection. Across countries the association patterns and strengths differed largely. With multivariable adjustment, resection rates decreased significantly in all countries except Slovenia and Estonia (prevalence ratio per year = 0.90–0.98), and the decreasing trends were consistently observed in various stratifications by age and location. Conclusion: In Europe and the US, resection patterns and trends largely varied across countries for mGCs, which were mostly less often resected in the early 21st century. Various resection-associated factors were shown, with greatly varying association patterns and strengths. Our report could aid to identify discrepancies in clinical practice and highlight the great need for further clarifying the role of resection in mGCs to enhance standardization of care.
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| 37. |
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| 38. |
- Avci, M., et al.
(author)
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The use of endoanchors in repair EVAR cases to improve proximal endograft fixation
- 2012
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In: Journal of Cardiovascular Surgery. - 0021-9509. ; 53:4, s. 419-426
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Journal article (peer-reviewed)abstract
- Aim. The aim of this paper was to evaluate short-term outcome of the use of endoanchors to secure the primary migrated endograft and additional extender cuffs to the aortic wall in patients with previous failed endovascular aortic aneurysm repair. Methods. Consecutive patients who needed proximal repair of a primary failed endograft due to migration (with or without type IA endoleaks) were treated with endoanchors, with or without additional extender cuffs. Data of this group were prospectively gathered in vascular referral centers that were early adopters of the endoanchor technique. Preprocedural and periprocedural data were prospectively gathered and retrospectively analyzed. Follow-up after endoanchor placement consisted of regular hospital visits, with computed tomography or duplex scanning at 1, 6, and 12 months. Results. From July 2010 to May 2011, 11 patients (8 men), mean age 77 years (range, 59-88 years), were treated with endoanchors for a failed primary endograft (2 Excluder endografts, 1 AneuRx endograft, and 8 Talent endografts) due to distal migration of the main body, with or without type IA endoleak. Revision consisted of using endoanchors to secure the body of the primary endograft to the aortic wall to avoid persistent migration. Most patients had additional proximal extender cuffs with suprarenal fixation, which were secured with endoanchors to the aortic wall and in some patients also to the primary endograft. A median of 6 endoanchors were implanted. All endoanchors were positioned correctly but one. One endoanchor dislodged but was successfully retrieved using an endovascular snare. During a mean follow-up of 10 months (range, 3-18 months) no endoanchor-related complications or renewed migration of the endografts occurred. Two patients underwent repeat intervention due to persistent type IA endoleak during follow-up. Conclusion. The use of endoanchors to secure migrated endografts to the aortic wall is safe and feasible and might help to overcome persistent migration of primary failed endografts. In combination with the use of sole extender cuffs the majority of proximal EVAR failures can be solved.
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| 39. |
- Bachoo, P., et al.
(author)
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Early outcome of endovascular aneurysm repair in challenging aortic neck morphology based on experience from the GREAT C3 registry
- 2013
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In: Journal of Cardiovascular Surgery. - 0021-9509 .- 1827-191X. ; 54:5, s. 573-580
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Journal article (peer-reviewed)abstract
- Aim. The aim of this paper was to evaluate early outcome of the GORE (R) EXCLUDER (R) AAA Endoprosthesis featuring C3 Delivery System in subjects with aortic neck anatomy outside IFU. Methods. Individual patient data prospectively collected over a 2 year period from the Global Registry for Endovascular Aortic Treatment (GREAT). For each subject a minimum data set was collected containing demographic, pre/intra- and postoperative variables. Main outcome measures were successful exclusion of the AAA and occurrence of any major endoleak at 1 month. In this study, outside IFU was defined as aortic neck length less than 15 mm and/or aortic neck angle greater than 60 degrees. Results. A total of 400 subjects, (86.6% male, mean age 73.9 years). Primary pathology was AAA in 94.2% with 98.2% undergoing EVAR as a primary procedure. Sixty-eight subjects underwent EVAR outside IFU (neck length <15 nun N.=32, neck angle >60 degrees N.=47 and neck length <15 nun and angle >60 degrees N.=11). The graft was successfully deployed within 5 nun of its intended location in 63 (94%) cases utilising a total of 33 repositioning episodes. Eight aortic cuffs were used, 5 to treat a type 1 endoleak. At 30 days we recorded 2 type 2 endoleaks both successfully treated and 1 type 1b also successfully treated. There were 2 deaths, one in each group. Conclusion. GORE (R) EXCLUDER (R) AAA Endoprosthesis featuring C3 Delivery System allows re-positioning to be performed safely in cases outside IFU. Repositioning is an effective operative manoeuvre and facilitates EVAR in challenging anatomy. Longer follow-up is required to evaluate the durability of these results at 30 days.
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| 40. |
- Darrow, Sabrina M., et al.
(author)
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The Association Between Psychiatric Disorders and Telomere Length : A Meta-Analysis Involving 14,827 Persons
- 2016
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In: Psychosomatic Medicine. - 0033-3174. ; 78:7, s. 776-787
-
Research review (peer-reviewed)abstract
- OBJECTIVE: This study examined the relationship between leukocyte telomere length (LTL), a marker of cell aging, and psychiatric disorders in adults compared with controls using meta-analytic methods. METHODS: Data were abstracted from studies examining the relationship between LTL and adult psychiatric disorders. In addition to an overall estimate of effect size, subgroup analyses and meta-regression were performed to examine whether covariates (including psychiatric diagnoses) moderated the estimate. RESULTS: A significant overall effect size showing LTL shortening was found across all psychiatric disorders (Hedge g = −0.50, p <.001). Subgroup analyses did not demonstrate significant differences in effect size based on individual covariates (psychiatric disorder, sex, age, or assay method). The meta-regression indicated that although type of disorder and, likely, age moderate the overall effect size, the heterogeneity between studies could not be explained by a model that included these variables as well as sex and assay method. Although not significantly different, posttraumatic stress disorder, anxiety disorders, and depressive disorders had comparatively larger effect sizes (−1.27, −0.53, and −0.55), and psychotic and bipolar disorders had comparatively smaller ones (−0.23 and −0.26). CONCLUSIONS: We observed a robust effect size of LTL shortening for psychiatric disorders as a whole compared with controls. The results were less straightforward regarding relative differences in the strength of this association by specific disorder. Future studies should focus on mechanisms explaining accelerated cell aging with psychiatric illness, defining directions (if any) of causality and elucidating possible differences in this association between disorders.
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| 41. |
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| 42. |
- Mastracci, T M, et al.
(author)
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Effect of Branch Stent Choice on Branch-related Outcomes in Complex Aortic Repair.
- 2016
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In: European journal of vascular and endovascular surgery. - : Elsevier BV. - 1532-2165 .- 1078-5884.
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The use of branched stent grafts for the treatment of thoracoabdominal aneurysms [TAAA] is increasing, but mating stent graft choice has not been studied. This study combined experience of five high volume centres to assess a preferred mating stent. METHODS: Data from five centres were retrospectively combined. Patients were included if they underwent stent graft for treatment of TAAA that used only branches to mate with visceral and renal vessels. All patients with fenestrations in their device were excluded. Perioperative details, reintervention, occlusion, and death were recorded. Outcome of occlusion or reintervention, as well as a composite outcome of any death, occlusion, or reintervention was planned using a per-patient, and per-branch analysis. RESULTS: In 235 included patients, there were 940 vessels available for placement of mating stent. The average age of included patients was 70 years (SD 7.9), and 179 of the 235 were male. Medical comorbidities included diabetes in 29/234 (12.4%), current smoker in 81/233 (34.8%), and COPD in 77/234 (32.9%). The primary stent deployed was self-expanding in 556 branches, balloon expandable in 231 branches, and was unknown in 92 branches. After a mean of 20.7 months (SD 25) follow-up, there have been 44 incidents of occlusion or reintervention, of which 40 culprit stents are known. Where the stent placed is known, the event rate in renal branches (35/437, 8%) is higher than that of visceral branches (8/443, 1.8%). There is no difference in occlusion or reintervention between self-expanding and balloon expandable stents (HR 0.95, p = .91) but there is a statistically significant difference between renal and visceral artery occlusions (HR 3.51, p = 0.001). CONCLUSION: There appears to be no difference in occlusion or reintervention rate for branch vessels mated with balloon expandable compared with self-expanding stents. Renal events appear to outnumber visceral events in this population.
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| 43. |
- 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
-
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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| 44. |
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| 45. |
- Verhoeven, E. L. G., et al.
(author)
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Real-world Performance of the New C3 Gore Excluder Stent-Graft : 1-year Results from the European C3 Module of the Global Registry for Endovascular Aortic Treatment (GREAT)
- 2014
-
In: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 48:2, s. 131-137
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Journal article (peer-reviewed)abstract
- Objectives: The European C3 module of the Global Registry for Endovascular Aortic Treatment (GREAT) provides "real-world" outcomes for the new C3 Gore Excluder stent-graft, and evaluates the new deployment mechanism. This report presents the 1-year results from 400 patients enrolled in this registry. Methods: Between August 2010 and December 2012, 400 patients (86.8% male, mean age 73.9 +/- 7.8 years) from 13 European sites were enrolled in this registry. Patient demographics, treatment indication, case planning, operative details including repositioning and technical results, and clinical outcome were analyzed. Results: Technical success was achieved in 396/400 (99%) patients. Two patients needed intraoperative open conversion, one for iliac rupture, the second because the stent-graft was pulled down during a cross-over catheterization in an angulated anatomy. Two patients required an unplanned chimney renal stent to treat partial coverage of the left renal artery because of upward displacement of the stent-graft. Graft repositioning occurred in 192/399 (48.1%) patients, most frequently for level readjustment with regard to the renal arteries, and less commonly for contralateral gate reorientation. Final intended position of the stent-graft below the renal arteries was achieved in 96.2% of patients. Thirty-day mortality was two (0.5%) patients. Early reintervention (<= 30 days) was required in two (0.5%) patients. Mean follow-up duration was 15.9 +/- 8.8 months (range 0-37 months). Late reintervention (>30 days) was required in 26 (6.5%) patients. Estimated freedom from reintervention at 1 year was 95.2% (95% CI 92.3-97%), and at 2 years 91.5% (95% CI 86.8-94.5%). Estimated patient survival at 1 year was 96% (95% CI 93.3-97.6%) and at 2 years 90.6% (95% CI 85.6-93.9%). Conclusions: Early real-world experience shows that the new C3 delivery system offers advantages in terms of device repositioning resulting in high deployment accuracy. Longer follow-up is required to confirm that this high deployment accuracy results in improved long-term durability.
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