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- Bravo, L, et al.
(author)
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- 2021
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- Tabiri, S, et al.
(author)
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- 2021
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- Khatri, C, et al.
(author)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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In: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Journal article (peer-reviewed)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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- Momozawa, Y, et al.
(author)
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IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
- 2018
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2427-
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Journal article (peer-reviewed)abstract
- GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach.
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- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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- Schael, S, et al.
(author)
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Precision electroweak measurements on the Z resonance
- 2006
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In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Research review (peer-reviewed)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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- Niemi, MEK, et al.
(author)
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- 2021
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- Tan, BYQ, et al.
(author)
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Left ventricular systolic dysfunction is associated with poor functional outcomes after endovascular thrombectomy
- 2021
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In: Journal of neurointerventional surgery. - : BMJ. - 1759-8486 .- 1759-8478. ; 13:6, s. 515-
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Journal article (peer-reviewed)abstract
- Endovascular thrombectomy (ET) has transformed acute ischemic stroke (AIS) therapy in patients with large vessel occlusion (LVO). Left ventricular systolic dysfunction (LVSD) decreases global cerebral blood flow and predisposes to hypoperfusion. We evaluated the relationship between LVSD, as measured by LV ejection fraction (LVEF), and clinical outcomes in patients with anterior cerebral circulation LVO who underwent ET.MethodsThis multicenter retrospective cohort study examined anterior circulation LVO AIS patients from six international stroke centers. LVSD was measured by assessment of the echocardiographic LVEF using Simpson’s biplane method of discs according to international guidelines. LVSD was defined as LVEF <50%. The primary outcome was defined as a good functional outcome using a modified Rankin Scale (mRS) of 0–2 at 3 months.ResultsWe included 440 AIS patients with LVO who underwent ET. On multivariate analyses, pre-existing diabetes mellitus (OR 2.05, 95% CI 1.24 to 3.39;p=0.005), unsuccessful reperfusion (Treatment in Cerebral Infarction (TICI) grade 0-2a) status (OR 4.21, 95% CI 2.04 to 8.66; p<0.001) and LVSD (OR 2.08, 95% CI 1.18 to 3.68; p=0.011) were independent predictors of poor functional outcomes at 3 months. On ordinal (shift) analyses, LVSD was associated with an unfavorable shift in the mRS outcomes (OR 2.32, 95% CI 1.52 to 3.53; p<0.001) after adjusting for age and ischemic heart disease.ConclusionAnterior circulation LVO AIS patients with LVSD have poorer outcomes after ET, suggesting the need to consider cardiac factors for ET, the degree of monitoring and prognostication post-procedure.
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- Teo, YN, et al.
(author)
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Combined balloon guide catheter, aspiration catheter, and stent retriever technique versus balloon guide catheter and stent retriever alone technique: a systematic review and meta-analysis
- 2023
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In: Journal of neurointerventional surgery. - : BMJ. - 1759-8486 .- 1759-8478. ; 15:2, s. 127-
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Journal article (peer-reviewed)abstract
- The use of a combination of balloon guide catheter (BGC), aspiration catheter, and stent retriever in acute ischemic stroke thrombectomy has not been shown to be better than a stent retriever and BGC alone, but this may be due to a lack of power in these studies. We therefore performed a meta-analysis on this subject.MethodsA systematic literature search was performed on PubMed, Scopus, Embase/Ovid, and the Cochrane Library from inception to October 20, 2021. Our primary outcomes were the rate of successful final reperfusion (Treatment in Cerebral Ischemia (TICI) 2c–3) and first pass effect (FPE, defined as TICI 2c–3 in a single pass). Secondary outcomes were 3 month functional independence (modified Rankin Scale score of 0–2), mortality, procedural complications, embolic complications, and symptomatic intracranial hemorrhage (SICH). A meta-analysis was performed using RevMan 5,4, and heterogeneity was assessed using the I2test.ResultsOf 1629 studies identified, five articles with 2091 patients were included. For the primary outcomes, FPE (44.9% vs 45.4%, OR 1.04 (95% CI 0.90 to 1.22), I2=57%) or final successful reperfusion (64.5% vs 68.6%, OR 0.98 (95% CI 0.81% to 1.20%), I2=85%) was similar between the combination technique and stent retriever only groups. However, the combination technique had significantly less rescue treatment (18.8% vs 26.9%; OR 0.70 (95% CI 0.54 to 0.91), I2=0%). This did not translate into significant differences in secondary outcomes in functional outcomes, mortality, emboli, complications, or SICH.ConclusionThere was no significant difference in successful reperfusion and FPE between the combined techniques and the stent retriever and BGC alone groups. Neither was there any difference in functional outcomes, complications, or mortality.
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