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- Bellenguez, C, et al.
(författare)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Tidskriftsartikel (refereegranskat)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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- Cooray, C, et al.
(författare)
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Safety and early outcomes after intravenous thrombolysis in acute ischemic stroke patients with prestroke disability
- 2021
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Ingår i: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949. ; 16:6, s. 710-718
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Tidskriftsartikel (refereegranskat)abstract
- There are limited data on intravenous thrombolysis treatment in ischemic stroke patients with prestroke disability.AimWe aimed to evaluate safety and outcomes of intravenous thrombolysis treatment in stroke patients with prestroke disability.MethodsWe analyzed 88,094 patients treated with intravenous thrombolysis, recorded in the Safe Implementation of Treatments in Stroke (SITS) International Thrombolysis Register between January 2003 and December 2017, with available NIHSS data at stroke-onset and after 24 h. Of them, 4566 patients (5.2%) had prestroke disability, defined as a modified Rankin Scale score of 3–5. Safety outcome measures included Symptomatic Intracerebral Hemorrhage, any type of parenchymal hematoma on 24 h imaging scans irrespective of clinical symptoms, and death within seven days. Early outcome measures were 24-h NIHSS improvement (≥4 from baseline to 24 h).ResultsPatients with prestroke disability were older, had more severe strokes, and more comorbidities than patients without prestroke disability. When comparing patients with prestroke disability with patients without prestroke disability, there was however no significant increase in adjusted odds for symptomatic intracerebral hemorrhage (adjusted odds ratio 0.83 (95% CI 0.60–1.15) (absolute difference in proportion 1.17% vs. 1.27%)) or for parenchymal hemorrhage (adjusted odds ratio 0.96 (0.83–1.11) (7.51% vs. 6.34%)). The prestroke disability group had a significantly lower-adjusted odds ratio for a 24-h NIHSS improvement (adjusted odds ratio 0.79 (0.73–0.85) (45.95% vs. 48.45%)) and a higher adjusted odds ratio for seven-day mortality (aOR 1.40 (1.21–1.61) (10.40% vs. 4.93%)).ConclusionsIntravenous thrombolysis in acute ischemic stroke patients with prestroke disability was not associated with an increased risk of symptomatic intracerebral hemorrhage or parenchymal hemorrhage. Prestroke disability was however associated with a higher risk of early mortality compared to patients without prestroke disability.
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- Tsivgoulis, G, et al.
(författare)
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Association of Baseline Hyperglycemia With Outcomes of Patients With and Without Diabetes With Acute Ischemic Stroke Treated With Intravenous Thrombolysis: A Propensity Score-Matched Analysis From the SITS-ISTR Registry
- 2019
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 68:9, s. 1861-1869
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Tidskriftsartikel (refereegranskat)abstract
- Available data from observational studies on the association of admission hyperglycemia (aHG) with outcomes of patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT) are contradictory, especially when stratified by diabetes mellitus (DM) history. We assessed the association of aHG (≥144 mg/dL) with outcomes stratified by DM history using propensity score–matched (PSM) data from the SITS-ISTR. The primary safety outcome was symptomatic intracranial hemorrhage (SICH); 3-month functional independence (FI) (modified Rankin Scale [mRS] scores 0–2) represented the primary efficacy outcome. Patients with and without aHG did not differ in baseline characteristics both in the non-DM (n = 12,318) and DM (n = 6,572) PSM subgroups. In the non-DM group, patients with aHG had lower 3-month FI rates (53.3% vs. 57.9%, P < 0.001), higher 3-month mortality rates (19.2% vs. 16.0%, P < 0.001), and similar symptomatic intracerebral hemorrhage (SICH) rates (1.7% vs. 1.8%, P = 0.563) compared with patients without aHG. Similarly, in the DM group, patients with aHG had lower rates of 3-month favorable functional outcome (mRS scores 0–1, 34.1% vs. 39.3%, P < 0.001) and FI (48.2% vs. 52.5%, P < 0.001), higher 3-month mortality rates (23.7% vs. 19.9%, P < 0.001), and similar SICH rates (2.2% vs. 2.7%, P = 0.224) compared with patients without aHG. In conclusion, aHG was associated with unfavorable 3-month clinical outcomes in patients with and without DM and AIS treated with IVT.
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