| 1. |
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| 2. |
- Power, M. J., et al.
(författare)
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Changes in fire regimes since the Last Glacial Maximum : an assessment based on a global synthesis and analysis of charcoal data
- 2008
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Ingår i: Climate Dynamics. - : Springer Science and Business Media LLC. - 0930-7575 .- 1432-0894. ; 30:7-8, s. 887-907
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Tidskriftsartikel (refereegranskat)abstract
- Fire activity has varied globally and continuously since the last glacial maximum (LGM) in response to long-term changes in global climate and shorter-term regional changes in climate, vegetation, and human land use. We have synthesized sedimentary charcoal records of biomass burning since the LGM and present global maps showing changes in fire activity for time slices during the past 21,000 years (as differences in charcoal accumulation values compared to pre-industrial). There is strong broad-scale coherence in fire activity after the LGM, but spatial heterogeneity in the signals increases thereafter. In North America, Europe and southern South America, charcoal records indicate less-than-present fire activity during the deglacial period, from 21,000 to ∼11,000 cal yr BP. In contrast, the tropical latitudes of South America and Africa show greater-than-present fire activity from ∼19,000 to ∼17,000 cal yr BP and most sites from Indochina and Australia show greater-than-present fire activity from 16,000 to ∼13,000 cal yr BP. Many sites indicate greater-than-present or near-present activity during the Holocene with the exception of eastern North America and eastern Asia from 8,000 to ∼3,000 cal yr BP, Indonesia and Australia from 11,000 to 4,000 cal yr BP, and southern South America from 6,000 to 3,000 cal yr BP where fire activity was less than present. Regional coherence in the patterns of change in fire activity was evident throughout the post-glacial period. These complex patterns can largely be explained in terms of large-scale climate controls modulated by local changes in vegetation and fuel load.
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| 3. |
- Tin, A, et al.
(författare)
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Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7173-
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Tidskriftsartikel (refereegranskat)abstract
- Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E–7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits.
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| 4. |
- Schlosser, P, et al.
(författare)
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Meta-analyses identify DNA methylation associated with kidney function and damage
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7174-
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.
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| 5. |
- Ikram, M. Arfan, et al.
(författare)
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Common variants at 6q22 and 17q21 are associated with intracranial volume
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 539-544
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Tidskriftsartikel (refereegranskat)abstract
- During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 x 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 x 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 x 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 x 10(-3) for 6q22 and 1.2 x 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.
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| 6. |
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| 7. |
- Taal, H. Rob, et al.
(författare)
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Common variants at 12q15 and 12q24 are associated with infant head circumference
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 532-538
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Tidskriftsartikel (refereegranskat)abstract
- To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
- Reipert, B M, et al.
(författare)
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The prospective Hemophilia Inhibitor PUP Study reveals distinct antibody signatures prior to FVIII inhibitor development
- 2020
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 4:22, s. 5785-5796
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Tidskriftsartikel (refereegranskat)abstract
- Preventing factor VIII (FVIII) inhibitors following replacement therapies with FVIII products in patients with hemophilia A remains an unmet medical need. Better understanding of the early events of evolving FVIII inhibitors is essential for risk identification and the design of novel strategies to prevent inhibitor development. The Hemophilia Inhibitor Previously Untreated Patients (PUPs) Study (HIPS; www.clinicaltrials.gov #NCT01652027) is the first prospective cohort study to evaluate comprehensive changes in the immune system during the first 50 exposure days (EDs) to FVIII in patients with severe hemophilia A. HIPS participants were enrolled prior to their first exposure to FVIII or blood products ("true PUPs") and were evaluated for different immunological and clinical parameters at specified time points during their first 50 EDs to a single source of recombinant FVIII. Longitudinal antibody data resulting from this study indicate that there are 4 subgroups of patients expressing distinct signatures of FVIII-binding antibodies. Subgroup 1 did not develop any detectable FVIII-binding immunoglobulin G (IgG) antibodies. Subgroup 2 developed nonneutralizing, FVIII-binding IgG1 antibodies, but other FVIII-binding IgG subclasses were not observed. Subgroup 3 developed transient FVIII inhibitors associated with FVIII-binding IgG1 antibodies, similar to subgroup 2. Subgroup 4 developed persistent FVIII inhibitors associated with an initial development of high-affinity, FVIII-binding IgG1 antibodies, followed by IgG3 and IgG4 antibodies. Appearance of FVIII-binding IgG3 was always associated with persistent FVIII inhibitors and the subsequent development of FVIII-binding IgG4. Some of the antibody signatures identified in HIPS could serve as candidates for early biomarkers of FVIII inhibitor development.
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| 12. |
- Wood, David A., et al.
(författare)
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Timing of Staged Nonculprit Artery Revascularization in Patients With ST-Segment Elevation Myocardial Infarction COMPLETE Trial
- 2019
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Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 74:22, s. 2713-2723
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The COMPLETE (Complete vs Culprit-only Revascularization to Treat Multi-vessel Disease After Early PCI for STEMI) trial demonstrated that staged nonculprit lesion percutaneous coronary intervention (PCI) reduced major cardiovascular (CV) events in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (CAD). OBJECTIVES The purpose of this study was to determine the effect of nonculprit-lesion PCI timing on major CV outcomes and also the time course of the benefit of complete revascularization. METHODS Following culprit-lesion PCI, 4,041 patients with STEMI and multivessel CAD were randomized to staged nonculprit-lesion PCI or culprit-lesion only PCI. Randomization was stratified according to investigator-planned timing of nonculprit-lesion PCI: during or after the index hospitalization. The first coprimary outcome was the composite of CV death or myocardial infarction (MI). In pre-specified analyses, hazard ratios (HRs) were calculated for each time stratum. Landmark analyses of the entire population were performed within 45 days and after 45 days. RESULTS For nonculprit-lesion PCI planned during the index hospitalization (actual time: median 1 day), CV death or MI was reduced with complete revascularization compared with culprit-lesion only PCI (HR: 0.77; 95% confidence interval [CI]: 0.59 to 1.00). For nonculprit lesion PCI planned to occur after hospital discharge (actual time: median 23 days), CV death or MI was also reduced with complete revascularization (HR: 0.69; 95% CI: 0.49 to 0.97; interaction p = 0.62). Landmark analyses demonstrated an HR of 0.86 (95% CI: 0.59 to 1.24) during the first 45 days and 0.69 (95% CI: 0.54 to 0.89) from 45 days to the end of follow-up for intended nonculprit lesion PCI versus culprit lesion only PCI. CONCLUSIONS Among STEMI patients with multivessel disease, the benefit of complete revascularization over culprit-lesion only PCI was consistent irrespective of the investigator-determined timing of nonculprit-lesion intervention. The benefit of complete revascularization on hard clinical outcomes emerged mainly over the long term. (C) 2019 by the American College of Cardiology Foundation.
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| 13. |
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| 14. |
- Chilunga, FP, et al.
(författare)
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DNA methylation as the link between migration and the major noncommunicable diseases: the RODAM study
- 2021
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 13:099, s. 653-666
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Tidskriftsartikel (refereegranskat)abstract
- Aim: We assessed epigenome-wide DNA methylation (DNAm) differences between migrant and non-migrant Ghanaians. Materials & methods: We used the Illumina Infinium® HumanMethylation450 BeadChip to profile DNAm of 712 Ghanaians in whole blood. We used linear models to detect differentially methylated positions (DMPs) associated with migration. We performed multiple post hoc analyses to validate our findings. Results: We identified 13 DMPs associated with migration (delta-beta values: 0.2–4.5%). Seven DMPs in CPLX2, EIF4E3, MEF2D, TLX3, ST8SIA1, ANG and CHRM3 were independent of extrinsic genomic influences in public databases. Two DMPs in NLRC5 were associated with duration of stay in Europe among migrants. All DMPs were biologically linked to migration-related factors. Conclusion: Our findings provide the first insights into DNAm differences between migrants and non-migrants.
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| 15. |
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| 16. |
- Chilunga, FP, et al.
(författare)
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Genome-wide DNA methylation analysis on C-reactive protein among Ghanaians suggests molecular links to the emerging risk of cardiovascular diseases
- 2021
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Ingår i: NPJ genomic medicine. - : Springer Science and Business Media LLC. - 2056-7944. ; 6:1, s. 46-
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Tidskriftsartikel (refereegranskat)abstract
- Molecular mechanisms at the intersection of inflammation and cardiovascular diseases (CVD) among Africans are still unknown. We performed an epigenome-wide association study to identify loci associated with serum C-reactive protein (marker of inflammation) among Ghanaians and further assessed whether differentially methylated positions (DMPs) were linked to CVD in previous reports, or to estimated CVD risk in the same population. We used the Illumina Infinium® HumanMethylation450 BeadChip to obtain DNAm profiles of blood samples in 589 Ghanaians from the RODAM study (without acute infections, not taking anti-inflammatory medications, CRP levels < 40 mg/L). We then used linear models to identify DMPs associated with CRP concentrations. Post-hoc, we evaluated associations of identified DMPs with elevated CVD risk estimated via ASCVD risk score. We also performed subset analyses at CRP levels ≤10 mg/L and replication analyses on candidate probes. Finally, we assessed for biological relevance of our findings in public databases. We subsequently identified 14 novel DMPs associated with CRP. In post-hoc evaluations, we found that DMPs in PC, BTG4 and PADI1 showed trends of associations with estimated CVD risk, we identified a separate DMP in MORC2 that was associated with CRP levels ≤10 mg/L, and we successfully replicated 65 (24%) of previously reported DMPs. All DMPs with gene annotations (13) were biologically linked to inflammation or CVD traits. We have identified epigenetic loci that may play a role in the intersection between inflammation and CVD among Ghanaians. Further studies among other Africans are needed to confirm our findings.
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| 17. |
- Danquah, Ina, et al.
(författare)
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Subgroups of adult-onset diabetes : a data-driven cluster analysis in a Ghanaian population
- 2023
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Adult-onset diabetes mellitus (here: aDM) is not a uniform disease entity. In European populations, five diabetes subgroups have been identified by cluster analysis using simple clinical variables; these may elucidate diabetes aetiology and disease prognosis. We aimed at reproducing these subgroups among Ghanaians with aDM, and establishing their importance for diabetic complications in different health system contexts. We used data of 541 Ghanaians with aDM (age: 25–70 years; male sex: 44%) from the multi-center, cross-sectional Research on Obesity and Diabetes among African Migrants (RODAM) Study. Adult-onset DM was defined as fasting plasma glucose (FPG) ≥ 7.0 mmol/L, documented use of glucose-lowering medication or self-reported diabetes, and age of onset ≥ 18 years. We derived subgroups by cluster analysis using (i) a previously published set of variables: age at diabetes onset, HbA1c, body mass index, HOMA-beta, HOMA-IR, positivity of glutamic acid decarboxylase autoantibodies (GAD65Ab), and (ii) Ghana-specific variables: age at onset, waist circumference, FPG, and fasting insulin. For each subgroup, we calculated the clinical, treatment-related and morphometric characteristics, and the proportions of objectively measured and self-reported diabetic complications. We reproduced the five subgroups: cluster 1 (obesity-related, 73%) and cluster 5 (insulin-resistant, 5%) with no dominant diabetic complication patterns; cluster 2 (age-related, 10%) characterized by the highest proportions of coronary artery disease (CAD, 18%) and stroke (13%); cluster 3 (autoimmune-related, 5%) showing the highest proportions of kidney dysfunction (40%) and peripheral artery disease (PAD, 14%); and cluster 4 (insulin-deficient, 7%) characterized by the highest proportion of retinopathy (14%). The second approach yielded four subgroups: obesity- and age-related (68%) characterized by the highest proportion of CAD (9%); body fat-related and insulin-resistant (18%) showing the highest proportions of PAD (6%) and stroke (5%); malnutrition-related (8%) exhibiting the lowest mean waist circumference and the highest proportion of retinopathy (20%); and ketosis-prone (6%) with the highest proportion of kidney dysfunction (30%) and urinary ketones (6%). With the same set of clinical variables, the previously published aDM subgroups can largely be reproduced by cluster analysis in this Ghanaian population. This method may generate in-depth understanding of the aetiology and prognosis of aDM, particularly when choosing variables that are clinically relevant for the target population.
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| 18. |
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| 19. |
- Jolly, Sanjit S., et al.
(författare)
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Thrombus Aspiration in ST Elevation Myocardial Infarction : An Individual Patient Meta-analysis
- 2017
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Ingår i: Circulation. - 0009-7322. ; 135, s. 143-152
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND—: Thrombus aspiration during percutaneous coronary intervention (PCI) for the treatment of ST elevation myocardial infarction (STEMI) has been widely used; however, recent trials have questioned its value and safety. In this meta-analysis, we, the trial investigators, aimed to pool the individual patient data from these trials to determine the benefits and risks of thrombus aspiration during PCI in patients with STEMI. METHODS—: Included were large (N≥1000) randomized controlled trials comparing manual thrombectomy vs. PCI alone in patients with STEMI. Individual patient data was provided by the leadership of each trial. The pre-specified primary efficacy outcome was cardiovascular (CV) mortality within 30 days and the primary safety outcome was stroke or transient ischemic attack (TIA) within 30 days. RESULTS—: The 3 eligible randomized trials (TAPAS, TASTE and TOTAL) enrolled 19,047 patients, of whom 18,306 underwent PCI and were included in the primary analysis. CV death at 30 days occurred in 221 (2.4%) of 9155 patients randomized to thrombus aspiration and 262 (2.9%) of 9151 randomized to PCI alone (hazard ratio (HR) 0.84; 95% CI 0.70-1.01, p=0.06). Stroke or TIA occurred in 66 (0.8%) randomized to thrombus aspiration and 46 (0.5%) randomized to PCI alone (odds ratio [OR] 1.43 95% CI 0.98-2.1, p=0.06). There were no significant differences in recurrent myocardial infarction, stent thrombosis, heart failure or target vessel revascularization. In the subgroup with high thrombus burden (TIMI thrombus grade ≥3) thrombus aspiration was associated with less CV death (170 [2.5%] vs. 205 [3.1%] HR 0.80; 95% CI 0.65-0.98, p =0.03), and with more stroke or TIA (55 [0.9%] vs. 34 [0.5%] OR 1.56; 95% CI 1.02-2.42, p=0.04). However, the interaction p-values were 0.32 and 0.34, respectively. CONCLUSIONS—: Routine thrombus aspiration during STEMI PCI did not improve clinical outcomes. In the high thrombus burden subgroup the trends toward reduced CV death and increased stroke or TIA provide a rationale for future trials of improved thrombus aspiration technologies in this high-risk subgroup. CLINICAL TRIAL REGISTRATION—: ClinicalTrials.gov identifier NCT02552407, PROSPERO CRD42015025936
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| 20. |
- Jolly, Sanjit S., et al.
(författare)
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Thrombus Aspiration in ST-Segment-Elevation Myocardial Infarction An Individual Patient Meta-Analysis : Thrombectomy Trialists Collaboration
- 2017
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 135:2, s. 143-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Thrombus aspiration during percutaneous coronary intervention (PCI) for the treatment of ST-segment-elevation myocardial infarction (STEMI) has been widely used; however, recent trials have questioned its value and safety. In this meta-analysis, we, the trial investigators, aimed to pool the individual patient data from these trials to determine the benefits and risks of thrombus aspiration during PCI in patients with ST-segment-elevation myocardial infarction. METHODS: Included were large (n >= 1000), randomized, controlled trials comparing manual thrombectomy and PCI alone in patients with ST-segment-elevation myocardial infarction. Individual patient data were provided by the leadership of each trial. The prespecified primary efficacy outcome was cardiovascular mortality within 30 days, and the primary safety outcome was stroke or transient ischemic attack within 30 days. RESULTS: The 3 eligible randomized trials (TAPAS [Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction], TASTE [Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia], and TOTAL [Trial of Routine Aspiration Thrombectomy With PCI Versus PCI Alone in Patients With STEMI]) enrolled 19 047 patients, of whom 18 306 underwent PCI and were included in the primary analysis. Cardiovascular death at 30 days occurred in 221 of 9155 patients (2.4%) randomized to thrombus aspiration and 262 of 9151 (2.9%) randomized to PCI alone (hazard ratio, 0.84; 95% confidence interval, 0.70-1.01; P=0.06). Stroke or transient ischemic attack occurred in 66 (0.8%) randomized to thrombus aspiration and 46 (0.5%) randomized to PCI alone (odds ratio, 1.43; 95% confidence interval, 0.98-2.10; P=0.06). There were no significant differences in recurrent myocardial infarction, stent thrombosis, heart failure, or target vessel revascularization. In the subgroup with high thrombus burden (TIMI [Thrombolysis in Myocardial Infarction] thrombus grade >= 3), thrombus aspiration was associated with fewer cardiovascular deaths (170 [2.5%] versus 205 [3.1%]; hazard ratio, 0.80; 95% confidence interval, 0.65-0.98; P=0.03) and with more strokes or transient ischemic attacks (55 [0.9%] versus 34 [0.5%]; odds ratio, 1.56; 95% confidence interval, 1.02-2.42, P=0.04). However, the interaction P values were 0.32 and 0.34, respectively. CONCLUSIONS: Routine thrombus aspiration during PCI for ST-segment-elevation myocardial infarction did not improve clinical outcomes. In the high thrombus burden group, the trends toward reduced cardiovascular death and increased stroke or transient ischemic attack provide a rationale for future trials of improved thrombus aspiration technologies in this high-risk subgroup.
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| 21. |
- Mahmoud, Karim D., et al.
(författare)
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Clinical impact of direct stenting and interaction with thrombus aspiration in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention : Thrombectomy Trialists Collaboration
- 2018
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 39:26, s. 2472-2479
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Preliminary studies suggest that direct stenting (DS) during percutaneous coronary intervention (PCI) may reduce microvascular obstruction and improve clinical outcome. Thrombus aspiration may facilitate DS. We assessed the impact of DS on clinical outcome and myocardial reperfusion and its interaction with thrombus aspiration among ST-segment elevation myocardial infarction (STEMI) patients undergoing PCI.Methods and results: Patient-level data from the three largest randomized trials on routine manual thrombus aspiration vs. PCI only were merged. A 1:1 propensity matched population was created to compare DS and conventional stenting. Synergy between DS and thrombus aspiration was assessed with interaction P-values in the final models. In the unmatched population (n= 17329), 32% underwent DS and 68% underwent conventional stenting. Direct stenting rates were higher in patients randomized to thrombus aspiration as compared with PCI only (41% vs. 22%; P < 0.001). Patients undergoing DS required less contrast (162 mL vs. 172 mL; P < 0.001) and had shorter fluoroscopy time (11.1 min vs. 13.3 min; P < 0.001). After propensity matching (n = 10944), no significant differences were seen between DS and conventional stenting with respect to 30-day cardiovascular death [1.7% vs. 1.9%; hazard ratio 0.88, 95% confidence interval (CI) 0.55-1.41; P=0.60; P-interaction = 0.96) and 30-day stroke or transient ischaemic attack (0.6% vs. 0.4%; odds ratio 1.02; 95% CI 0.14-7.54; P= 0.99; P-interaction = 0.81). One-year results were similar. No significant differences were seen in electrocardiographic and angiographic myocardial reperfusion measures.Conclusion: Direct stenting rates were higher in patients randomized to thrombus aspiration. Clinical outcomes and myocardial reperfusion measures did not differ significantly between DS and conventional stenting and there was no interaction with thrombus aspiration.
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| 22. |
- Viborg Lindskrog, Sia, et al.
(författare)
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An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n=834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations are significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration is associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirms the higher infiltration of class 2b tumors and demonstrates an association between higher immune cell infiltration and lower recurrence rates. Finally, the independent prognostic value of the transcriptomic classes is documented in 1228 validation samples using a single sample classification tool. The classifier provides a framework for biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials.
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