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| 2. |
- Carrera, Caty, et al.
(författare)
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Validation of a clinical-genetics score to predict hemorrhagic transformations after rtPA.
- 2019
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Ingår i: Neurology. - 1526-632X. ; 93:9
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Tidskriftsartikel (refereegranskat)abstract
- To validate the Genot-PA score, a clinical-genetic logistic regression score that stratifies the thrombolytic therapy safety, in a new cohort of patients with stroke.We enrolled 1,482 recombinant tissue plasminogen activator (rtPA)-treated patients with stroke in Spain and Finland from 2003 to 2016. Cohorts were analyzed on the basis of ethnicity and therapy: Spanish patients treated with IV rtPA within 4.5 hours of onset (cohort A and B) or rtPA in combination with mechanical thrombectomy within 6 hours of onset (cohort C) and Finnish participants treated with IV rtPA within 4.5 hours of onset (cohort D). The Genot-PA score was calculated, and hemorrhagic transformation (HT) and parenchymal hematoma (PH) risks were determined for each score stratum.Genot-PA score was tested in 1,324 (cohort A, n = 726; B, n = 334; C, n = 54; and D, n = 210) patients who had enough information to complete the score. Of these, 213 (16.1%) participants developed HT and 85 (6.4%) developed PH. In cohorts A, B, and D, HT occurrence was predicted by the score (p = 2.02 × 10-6, p = 0.023, p = 0.033); PH prediction was associated in cohorts A through C (p = 0.012, p = 0.034, p = 5.32 × 10-4). Increased frequency of PH events from the lowest to the highest risk group was found (cohort A 4%-15.7%, cohort B 1.5%-18.2%, cohort C 0%-100%). The best odds ratio for PH prediction in the highest-risk group was obtained in cohort A (odds ratio 5.16, 95% confidence interval 1.46-18.08, p = 0.009).The Genot-PA score predicts HT in patients with stroke treated with IV rtPA. Moreover, in an exploratory study, the score was associated with PH risk in mechanical thrombectomy-treated patients.
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| 3. |
- Hewitt, Graeme, et al.
(författare)
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Defective ALC1 nucleosome remodeling confers PARPi sensitization and synthetic lethality with HRD
- 2021
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Ingår i: Molecular Cell. - : Cell Press. - 1097-2765 .- 1097-4164. ; 81:4, s. 767-783.e11
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Tidskriftsartikel (refereegranskat)abstract
- Chromatin is a barrier to efficient DNA repair, as it hinders access and processing of certain DNA lesions. ALC1/CHD1L is a nucleosome-remodeling enzyme that responds to DNA damage, but its precise function in DNA repair remains unknown. Here we report that loss of ALC1 confers sensitivity to PARP inhibitors, methyl-methanesulfonate, and uracil misincorporation, which reflects the need to remodel nucleosomes following base excision by DNA glycosylases but prior to handover to APEX1. Using CRISPR screens, we establish that ALC1 loss is synthetic lethal with homologous recombination deficiency (HRD), which we attribute to chromosome instability caused by unrepaired DNA gaps at replication forks. In the absence of ALC1 or APEX1, incomplete processing of BER intermediates results in post-replicative DNA gaps and a critical dependence on HR for repair. Hence, targeting ALC1 alone or as a PARP inhibitor sensitizer could be employed to augment existing therapeutic strategies for HRD cancers.
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| 4. |
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| 5. |
- Marto, João Pedro, et al.
(författare)
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Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:7
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT).Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60).Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis.The study was registered under ClinicalTrials.gov identifier NCT04895462.
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| 6. |
- Segura, Laura, et al.
(författare)
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Anti-inflammatory activity of dichloromethane extract of Heterotheca inuloides in vivo and in vitro
- 2000
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Ingår i: Planta Medica. - : Georg Thieme Verlag KG. - 0032-0943 .- 1439-0221. ; 66:6, s. 553-555
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Tidskriftsartikel (refereegranskat)abstract
- The dichloromethane extract from the dried flowers of Heterotheca inuloides Cass. was investigated on several pharmacological models of inflammation in vivo and in vitro. It showed anti-inflammatory activity on the croton oil-induced oedema test in mouse ear, at 1 mg/ear. The compound isolated from this extract, 7-hydroxy-3,4-dihydrocadalin, showed anti-inflammatory effect on the same experimental model (ED50 of 0.9 mumol/ear), as well as on COX-1 and COX-2 catalysed prostaglandin biosynthesis assays, with IC50 values of 22 microM and 526 microM, respectively. No effect was observed on carrageenan-induced oedema and on fMLP/PAF-induced exocytosis of human neutrophils. The COX-1 inhibitory effect showed by 7-hydroxy-3,4-dihydrocadalin might be related to the anti-inflammatory activity on the topical oedema induced by croton oil.
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| 7. |
- Kanai, M, et al.
(författare)
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- 2023
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