| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Bravo, L, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 7. |
- Tabiri, S, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 8. |
- Campbell, PJ, et al.
(författare)
-
Pan-cancer analysis of whole genomes
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
- Bulluck, H, et al.
(författare)
-
Independent Predictors of Cardiac Mortality and Hospitalization for Heart Failure in a Multi-Ethnic Asian ST-segment Elevation Myocardial Infarction Population Treated by Primary Percutaneous Coronary Intervention
- 2019
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10072-
-
Tidskriftsartikel (refereegranskat)abstract
- We aimed to identify independent predictors of cardiac mortality and hospitalization for heart failure (HHF) from a real-world, multi-ethnic Asian registry [the Singapore Myocardial Infarction Registry] of ST-segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention. 11,546 eligible STEMI patients between 2008 and 2015 were identified. In-hospital, 30-day and 1-year cardiac mortality and 1-year HHF rates were 6.4%, 6.8%, 8.3% and 5.2%, respectively. From the derivation cohort (70% of patients), age, Killip class and cardiac arrest, creatinine, hemoglobin and troponin on admission and left ventricular ejection fraction (LVEF) during hospitalization were predictors of in-hospital, 30-day and 1-year cardiac mortality. Previous ischemic heart disease (IHD) was a predictor of in-hospital and 30-day cardiac mortality only, whereas diabetes was a predictor of 1-year cardiac mortality only. Age, previous IHD and diabetes, Killip class, creatinine, hemoglobin and troponin on admission, symptom-to-balloon-time and LVEF were predictors of 1-year HHF. The c-statistics were 0.921, 0.901, 0.881, 0.869, respectively. Applying these models to the validation cohort (30% of patients) showed good fit and discrimination (c-statistic 0.922, 0.913, 0.903 and 0.855 respectively; misclassification rate 14.0%, 14.7%, 16.2% and 24.0% respectively). These predictors could be incorporated into specific risk scores to stratify reperfused STEMI patients by their risk level for targeted intervention.
|
|
| 12. |
- Khatri, C, et al.
(författare)
-
Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
-
Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
-
Tidskriftsartikel (refereegranskat)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
|
|
| 13. |
|
|
| 14. |
- Sim, HW, et al.
(författare)
-
Beta-blockers and renin-angiotensin system inhibitors in acute myocardial infarction managed with inhospital coronary revascularization
- 2020
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 15184-
-
Tidskriftsartikel (refereegranskat)abstract
- Pivotal trials of beta-blockers (BB) and angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) in acute myocardial infarction (AMI) were largely conducted prior to the widespread adoption of early revascularization. A total of 15,073 patients with AMI who underwent inhospital coronary revascularization from January 2007 to December 2013 were analyzed. At 12 months, BB was significantly associated with a lower incidence of major adverse cardiovascular events (MACE, adjusted HR 0.80, 95% CI 0.70–0.93) and all-cause mortality (adjusted HR 0.69, 95% CI 0.55–0.88), while ACEI/ARB was significantly associated with lower all-cause mortality (adjusted HR 0.80, 95% CI 0.66–0.98) and heart failure (HF) hospitalization (adjusted HR 0.80, 95% CI 0.68–0.95). Combined BB and ACEI/ARB use was associated with the lowest incidence of MACE (adjusted HR 0.70, 95% CI 0.57–0.86), all-cause mortality (adjusted HR 0.55, 95% CI 0.40–0.77) and HF hospitalization (adjusted HR 0.64, 95% CI 0.48–0.86). This were consistent for left ventricular ejection fraction < 50% or ≥ 50%. In conclusion, in AMI managed with revascularization, both BB and ACEI/ARB were associated with a lower incidence of 12-month all-cause mortality. Combined BB and ACEI/ARB was associated with the lowest incidence of all-cause mortality and HF hospitalization.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
- Feng, HL, et al.
(författare)
-
Associations of timing of physical activity with all-cause and cause-specific mortality in a prospective cohort study
- 2023
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 930-
-
Tidskriftsartikel (refereegranskat)abstract
- There is a growing interest in the role of timing of daily behaviors in improving health. However, little is known about the optimal timing of physical activity to maximize health benefits. We perform a cohort study of 92,139 UK Biobank participants with valid accelerometer data and all-cause and cause-specific mortality outcomes, comprising over 7 years of median follow-up (638,825 person-years). Moderate-to-vigorous intensity physical activity (MVPA) at any time of day is associated with lower risks for all-cause, cardiovascular disease, and cancer mortality. In addition, compared with morning group (>50% of daily MVPA during 05:00-11:00), midday-afternoon (11:00-17:00) and mixed MVPA timing groups, but not evening group (17:00-24:00), have lower risks of all-cause and cardiovascular disease mortality. These protective associations are more pronounced among the elderly, males, less physically active participants, or those with preexisting cardiovascular diseases. Here, we show that MVPA timing may have the potential to improve public health.
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
- Kvedaraite, E, et al.
(författare)
-
Notch-dependent cooperativity between myeloid lineages promotes Langerhans cell histiocytosis pathology
- 2022
-
Ingår i: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 7:78, s. eadd3330-
-
Tidskriftsartikel (refereegranskat)abstract
- Langerhans cell histiocytosis (LCH) is a potentially fatal neoplasm characterized by the aberrant differentiation of mononuclear phagocytes, driven by mitogen-activated protein kinase (MAPK) pathway activation. LCH cells may trigger destructive pathology yet remain in a precarious state finely balanced between apoptosis and survival, supported by a unique inflammatory milieu. The interactions that maintain this state are not well known and may offer targets for intervention. Here, we used single-cell RNA-seq and protein analysis to dissect LCH lesions, assessing LCH cell heterogeneity and comparing LCH cells with normal mononuclear phagocytes within lesions. We found LCH discriminatory signatures pointing to senescence and escape from tumor immune surveillance. We also uncovered two major lineages of LCH with DC2- and DC3/monocyte-like phenotypes and validated them in multiple pathological tissue sites by high-content imaging. Receptor-ligand analyses and lineage tracing in vitro revealed Notch-dependent cooperativity between DC2 and DC3/monocyte lineages during expression of the pathognomonic LCH program. Our results present a convergent dual origin model of LCH with MAPK pathway activation occurring before fate commitment to DC2 and DC3/monocyte lineages and Notch-dependent cooperativity between lineages driving the development of LCH cells.
|
|
| 39. |
- Lee, KS, et al.
(författare)
-
Bridging thrombolysis improves survival rates at 90 days compared with direct mechanical thrombectomy alone in acute ischemic stroke due to basilar artery occlusion: a systematic review and meta-analysis of 1096 patients
- 2023
-
Ingår i: Journal of neurointerventional surgery. - : BMJ. - 1759-8486 .- 1759-8478. ; 15:10, s. 1039-1045
-
Tidskriftsartikel (refereegranskat)abstract
- Mechanical thrombectomy (MT) is an effective treatment for patients with acute ischemic stroke (AIS) from basilar artery occlusion (BAO).ObjectiveTo compare the clinical outcomes of MT, with and without bridging intravenous thrombolysis (IVT), in acute BAO through a systematic review and meta-analysis of the current literature.MethodsSystematic searches of Medline, EMBASE, and Cochrane Central were undertaken on August 1, 2022. Good functional outcome defined as 90-day modified Rankin Scale score 0–2 was the primary outcome measure. Secondary outcome measures were 90-day mortality, successful post-thrombectomy recanalization (modified Thrombolysis in Cerebral Infarction score ≥2b), symptomatic intracranial hemorrhage (sICH), and subarachnoid hemorrhage (SAH).ResultsThree studies reporting 1096 patients with BAO AIS were included in the meta-analysis. No significant differences in good functional outcome were detected between the two groups (RR=1.28 (95% CI 0.86 to 1.92); p=0.117). However, specifically patients with large artery atherosclerosis (LAA) benefited from bridging IVT (OR=2.52 (95% CI 1.51 to 4.22); p<0.001) with better functional outcomes. There was a significantly lower 90-day mortality rate for patients who underwent bridging IVT compared with MT alone (RR=0.70 (95% CI 0.62 to 0.80); p=0.008). No significant differences were detected in rates of post-treatment recanalization (RR=1.01 (95% CI 0.35 to 2.91); p=0.954), sICH (RR=0.96 (95% CI 0.66 to 1.42); p=0.724), and SAH (RR=0.93 (95% CI 0.31 to 2.83); p=0.563).ConclusionsIn patients with AIS due to BAO, bridging IVT was associated with lower mortality rates at 90 days, compared with direct MT. There were no improved functional outcomes or increased sICH or SAH between both arms, However, patients with LAA benefited from bridging IVT, with better functional outcomes.
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
|
|
| 44. |
- Myint, MZ, et al.
(författare)
-
Internal cerebral vein asymmetry is an independent predictor of poor functional outcome in endovascular thrombectomy
- 2022
-
Ingår i: Journal of neurointerventional surgery. - : BMJ. - 1759-8486 .- 1759-8478. ; 14:7, s. 683-687
-
Tidskriftsartikel (refereegranskat)abstract
- Endovascular thrombectomy (EVT) in large vessel occlusion (LVO) in anterior circulation acute ischaemic stroke (AIS) results in good functional outcomes in only approximately 60% of the patients. Internal cerebral veins (ICVs) are easily visible, with a consistent midline location, and are linked to stroke outcomes. We hypothesize that ICV asymmetry on multiphasic CT angiogram (mCTA) can be an adjunctive predictor for poor functional outcomes.MethodsWe studied consecutive AIS patients from 2017 to 2019 with anterior circulation LVO treated with EVT regardless of intravenous thrombolysis. Asymmetrical ICV was defined as the presence of hypodensity (less opacification) on the ipsilateral occlusion side as compared with the contralateral side. The primary outcome was modified Rankin Score (mRS) score at 3 months. Secondary outcomes were good recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3), symptomatic hemorrhage, and mortality.ResultsA total of 185 patients were included with a median age of 70 years (IQR 59–77); 87 patients (47%) were female. 82 patients (44.3%) achieved good functional outcomes (mRS 0–2) at 3 months. On multivariate analysis, National Institutes of Health Stroke Scale (NIHSS) (OR 1.076, 95% CI 1.015 to 1.140; p<0.013), poor collateral score (OR 0.285, 95% CI 0.162 to 0.501; p<0.001), asymmetrical ICV on the peak venous phase (OR 2.47, 95% CI 1.115 to 5.471; p<0.026), and late venous phase of the mCTA (OR 2.642, 95% CI 1.161 to 6.016; p<0.021) were independent risks factors of poor outcomes.ConclusionICV asymmetry is a novel radiological sign which is independently associated with poor functional outcomes in EVT, even after correction for collateral circulation. Further studies are needed to validate this finding.
|
|
| 45. |
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
|
|
| 49. |
|
|
| 50. |
|
|
