GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Stroke genetics informs drug discovery and risk prediction across ancestries
    Springer Science and Business Media LLC ; 2022
    In:  Nature Vol. 611, No. 7934 ( 2022-11-03), p. 115-123
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 611, No. 7934 ( 2022-11-03), p. 115-123
    Abstract: Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry 1,2 . Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated ( P   〈  0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis 3 , and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN ) and variants (such as at GRK5 and NOS3 ). Using a three-pronged approach 4 , we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry 5 . Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-022-05165-3
    RVK:
    TA 1000
    RVK:
    UA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
    SSG: 11
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Publisher Correction: Stroke genetics informs drug discovery and risk prediction across ancestries
    Springer Science and Business Media LLC ; 2022
    In:  Nature Vol. 612, No. 7938 ( 2022-12-01), p. E7-E7
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 612, No. 7938 ( 2022-12-01), p. E7-E7
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-022-05492-5
    RVK:
    TA 1000
    RVK:
    UA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
    SSG: 11
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Intra-arterial Administration of Microbubbles and Continuous 2-MHz Ultrasound Insonation to Enhance Intra-arterial Thrombolysis
    Wiley ; 2009
    In:  Journal of Neuroimaging Vol. 20, No. 3 ( 2009-02-17), p. 224-227
    Details
    In: Journal of Neuroimaging, Wiley, Vol. 20, No. 3 ( 2009-02-17), p. 224-227
    Type of Medium: Online Resource
    ISSN: 1051-2284 , 1552-6569
    URL: Issue
    URL: Article
    DOI: 10.1111/jon.2010.20.issue-3
    DOI: 10.1111/j.1552-6569.2008.00357.x
    Language: English
    Publisher: Wiley
    Publication Date: 2009
    detail.hit.zdb_id: 2035400-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Transcranial Doppler Monitoring of Transcervical Carotid Stenting With Flow Reversal Protection : A Novel Carotid Revascularization Technique
    Ovid Technologies (Wolters Kluwer Health) ; 2006
    In:  Stroke Vol. 37, No. 11 ( 2006-11), p. 2846-2849
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 37, No. 11 ( 2006-11), p. 2846-2849
    Abstract: Background and Purpose— Transfemoral carotid stenting, despite becoming very frequent, has some limitations such as difficult groin access in few patients, lack of distal protection during filter placement, or embolization despite protection. Transcervical stenting (TCS) is a novel technique during which a common carotid to jugular vein shunt is placed creating a protective reversal flow in the internal carotid artery after proximal common carotid artery (CCA) clamping. We aim to study, with transcranial Doppler (TCD), cerebral flow changes and microemboli detection during transcervical stenting. Methods— From September 2005 to March 2006, of 65 consecutive patients eligible for carotid revascularization, 23 were considered high risk (sapphire criteria) and underwent TCS. Neurologic examination was performed before and after the procedure by a neurologist and a preprocedure vascular reactivity TCD examination was done in all patients. Results— After CCA clamping, flow inversion was observed in the anterior cerebral artery, supplying blood to the middle cerebral artery (MCA) and internal carotid artery (reversal). TCD did not detect any air/solid emboli during stent deployment and angioplasty confirming the reversal flow protection hypothesis. Mean reversal flow time was 15.4 minutes; in all cases, substantial MCA flow was present during CCA clamping (initial mean velocity 30 cm/s), and a slow gradual increase was observed traducing collateral flow recruitment (mean velocity after 5 minutes 36 cm/s, P 〈 0.001). Flow increase was observed in all patients except in those with preprocedural exhausted ipsilateral vascular reactivity (16% versus 2%, P =0.036). The only in-procedure complication was one transient ischemic attack. After CCA unclamping, normal antegrade flow was restored in anterior cerebral artery and mean final MCA velocity increased 16% according to preprocedure flow. Conclusions— TCS with protective internal carotid artery flow reversal can eliminate showers of micoremboli during stent deployment making it a promising carotid revascularization technique in high-risk patients with carotid stenosis.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/01.STR.0000244781.68371.59
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2006
    detail.hit.zdb_id: 1467823-8
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Matrix metalloproteinase—9 concentration after spontaneous intracerebral hemorrhage
    Journal of Neurosurgery Publishing Group (JNSPG) ; 2003
    In:  Journal of Neurosurgery Vol. 99, No. 1 ( 2003-07), p. 65-70
    Details
    In: Journal of Neurosurgery, Journal of Neurosurgery Publishing Group (JNSPG), Vol. 99, No. 1 ( 2003-07), p. 65-70
    Abstract: Object. Matrix metalloproteinases (MMPs) are overexpressed in the presence of some neurological diseases in which blood—brain barrier disruption exists. The authors investigated the MMP-9 concentration in patients after acute intracerebral hemorrhage (ICH) and its relation to perihematomal edema (PHE). Methods. Concentrations of MMP-9 and related proteins were determined in plasma by performing an enzyme-linked immunosorbent assay of samples drawn after hospital admission ( 〈 24 hours after stroke) from 57 patients with ICH. The diagnosis of ICH was made on the basis of findings on computerized tomography (CT) scans. The volumes of ICH and PHE were measured on baseline and follow-up CT scans at the same time that the patient's neurological status was assessed using the Canadian Stroke Scale and the Glasgow Coma Scale. Increased expression of MMP-9 was found among patients with ICH. In cases of deep ICH, MMP-9 was significantly associated with PHE volume (r = 0.53; p = 0.01) and neurological worsening (237.4 compared with 111.3 ng/ml MMP-9; p = 0.04). A logistic regression model focusing on the study of absolute PHE volume showed ICH volume as an independent predictor (odds ratio [OR] 3.37; 95% confidence interval [CI] 1.1–10.3; p = 0.03). A second analysis of relative PHE volume (absolute PHE volume/ICH volume) in patients with deep ICH demonstrated that the only factor related to it was MMP-9 concentration (OR 11.6; 95% CI 1.5–89.1; p = 0.018). Conclusions. Expression of MMP-9 is raised after acute spontaneous ICH. Among patients with deep ICH this increase is associated with PHE and the development of neurological worsening within the acute stage.
    Type of Medium: Online Resource
    ISSN: 0022-3085
    URL: Article
    DOI: 10.3171/jns.2003.99.1.0065
    RVK:
    XA 10000
    RVK:
    XA 55270
    Language: Unknown
    Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
    Publication Date: 2003
    detail.hit.zdb_id: 2026156-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Table_3.DOCX
    Frontiers Media SA ; 2022
    In:  Frontiers in Cardiovascular Medicine Vol. 9 ( 2022-7-8)
    Details
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2022-7-8)
    Abstract: Occult atrial fibrillation (AF) is one of the major causes of embolic stroke of undetermined source (ESUS). Knowing the underlying etiology of an ESUS will reduce stroke recurrence and/or unnecessary use of anticoagulants. Understanding cardioembolic strokes (CES), whose main cause is AF, will provide tools to select patients who would benefit from anticoagulants among those with ESUS or AF. We aimed to discover novel loci associated with CES and create a polygenetic risk score (PRS) for a more efficient CES risk stratification. Methods Multitrait analysis of GWAS (MTAG) was performed with MEGASTROKE-CES cohort ( n = 362,661) and AF cohort ( n = 1,030,836). We considered significant variants and replicated those variants with MTAG p -value & lt; 5 × 10 −8 influencing both traits (GWAS-pairwise) with a p -value & lt; 0.05 in the original GWAS and in an independent cohort ( n = 9,105). The PRS was created with PRSice-2 and evaluated in the independent cohort. Results We found and replicated eleven loci associated with CES. Eight were novel loci. Seven of them had been previously associated with AF, namely, CAV1, ESR2, GORAB, IGF1R, NEURL1, WIPF1 , and ZEB2 . KIAA1755 locus had never been associated with CES/AF, leading its index variant to a missense change (R1045W). The PRS generated has been significantly associated with CES improving discrimination and patient reclassification of a model with age, sex, and hypertension. Conclusion The loci found significantly associated with CES in the MTAG, together with the creation of a PRS that improves the predictive clinical models of CES, might help guide future clinical trials of anticoagulant therapy in patients with ESUS or AF.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fcvm.2022.940696
    DOI: 10.3389/fcvm.2022.940696.s001
    DOI: 10.3389/fcvm.2022.940696.s002
    DOI: 10.3389/fcvm.2022.940696.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2781496-8
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Lower concentrations of thrombin-antithrombin complex (TAT) correlate to higher recanalisation rates among ischaemic stroke patients treated with t-PA
    Georg Thieme Verlag KG ; 2009
    In:  Thrombosis and Haemostasis Vol. 102, No. 10 ( 2009), p. 759-764
    Details
    In: Thrombosis and Haemostasis, Georg Thieme Verlag KG, Vol. 102, No. 10 ( 2009), p. 759-764
    Abstract: An elevated concentration of the thrombin-antithrombin complex (TAT) has been associated with high mortality rates and poor outcome in ischaemic stroke patients treated with tissue plasminogen activator (t-PA). Moreover, antithrombin drugs have been tested in combination with t-PA in the acute phase of ischaemic stroke to increase treatment efficacy. We aimed to study whether poor outcome associated with TAT among ischaemic stroke patients treated with t-PA could be due to the effects of this complex on recanalisation rates of the middle cerebral artery (MCA) and on haemorrhagic transformation. The TAT levels of 89 patients having a proximal MCA occlusion were measured by ELISA, and the patients were then treated with t-PA. Complete recanalisation was diagnosed by transcranial Doppler (TCD) at 1, 2 and 6 hours post-t-PA infusion and haemorrhagic transformation was identified by computed tomography (CT). Lower levels of TAT were associated with better recanalisation rates at all time-points (1 hour: OR = 24.8 95% CI 1.4–434.8, p = 0.028;2 hours:OR = 6.3 95% CI 1.5–27, p = 0.014; 6 hours: OR = 6.4 95% CI 1.5–26.5, p = 0.011) after adjustment for stroke risk factors. However, no correlation was found between TAT concentration and haemorrhagic transformation. The elevated mortality rates previously observed in patients with high levels of TAT might have been due to revascularisation resistance. Low levels of TAT are not associated with an increase in haemorrhagic complications after t-PA, indicating that the combination of thrombin blockers and t-PA could be a safe and effective treatment for ischaemic stroke in the future.
    Type of Medium: Online Resource
    ISSN: 0340-6245 , 2567-689X
    URL: Article
    DOI: 10.1160/TH08-06-0398
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2009
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Thrombolysis in Anterior Versus Posterior Circulation Strokes: Timing of Recanalization, Ischemic Tolerance, and Other Differences
    Wiley ; 2011
    In:  Journal of Neuroimaging Vol. 21, No. 2 ( 2011-04), p. 108-112
    Details
    In: Journal of Neuroimaging, Wiley, Vol. 21, No. 2 ( 2011-04), p. 108-112
    Type of Medium: Online Resource
    ISSN: 1051-2284
    URL: Issue
    URL: Article
    DOI: 10.1111/jon.2011.21.issue-2
    DOI: 10.1111/j.1552-6569.2009.00462.x
    Language: English
    Publisher: Wiley
    Publication Date: 2011
    detail.hit.zdb_id: 2035400-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Effects of Admission Hyperglycemia on Stroke Outcome in Reperfused Tissue Plasminogen Activator–Treated Patients
    Ovid Technologies (Wolters Kluwer Health) ; 2003
    In:  Stroke Vol. 34, No. 5 ( 2003-05), p. 1235-1240
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 34, No. 5 ( 2003-05), p. 1235-1240
    Abstract: Background and Purpose— We sought to investigate the impact of hyperglycemia before reperfusion on long-term outcome in patients treated with intravenous tissue plasminogen activator (tPA). Methods— Of 268 consecutive patients with a nonlacunar middle cerebral artery (MCA) stroke evaluated at 〈 3 hours after onset, 73 (27.2%) received intravenous tPA. Serum glucose was determined at baseline before tPA administration. Hyperglycemia was defined as a glucose level 〉 140 mg/dL. National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and 24 hours. Transcranial Doppler monitoring of recanalization and reocclusion was conducted during the first 24 hours. Total infarct volume was measured on CT at day 5 to 7. Modified Rankin Scale was used to assess outcome at 3 months. Results— Median NIHSS score was 17. At baseline, 31 patients (42.5%) were hyperglycemic and 42 (57.5%) normoglycemic. Early reperfusion ( 〈 6 hours) occurred in 43 patients (58.9%). Admission blood glucose correlated negatively with the degree of neurological improvement at 24 hours in reperfused ( r =−0.43; P =0.019) but not in nonreperfused ( r =−0.20; P =0.21) tPA-treated patients. Increased age ( P =0.014), history of diabetes mellitus ( P =0.043), admission glucose 〉 140 mg/dL ( P =0.002), and early reocclusion ( P =0.004) were factors associated with poor outcome among reperfused patients. A logistic regression modeling revealed that only admission glucose value 〉 140 mg/dL (odds ratio, 8.4; 95% CI, 1.76 to 40.02; P =0.005) emerged as an independent predictor of poor outcome despite tPA-induced recanalization. In patients with 6-hour persistent MCA occlusion, baseline NIHSS score 〉 15 points ( P =0.011) and proximal MCA occlusion ( P =0.039) were variables associated with poor outcome on univariate analysis. In a logistic regression model, only NIHSS score 〉 15 points (odds ratio, 11.9; 95% CI, 1.48 to 97.1; P =0.032) remained as an independent predictor of poor outcome and functional dependence at 3 months in nonreperfused tPA-treated patients. Conclusions— Hyperglycemia before reperfusion may in part counterbalance the beneficial effect of early restoration of blood flow, which translates into a worse outcome in hyperglycemic patients despite tPA-induced recanalization.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/01.STR.0000068406.30514.31
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2003
    detail.hit.zdb_id: 1467823-8
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Prior Statin Use May Be Associated With Improved Stroke Outcome After Tissue Plasminogen Activator
    Ovid Technologies (Wolters Kluwer Health) ; 2007
    In:  Stroke Vol. 38, No. 3 ( 2007-03), p. 1076-1078
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 38, No. 3 ( 2007-03), p. 1076-1078
    Abstract: Background and Purpose— Statins may exert some neuroprotection, because use before stroke onset has been related to better outcome and reduced mortality. The purpose of this study was to evaluate whether patients who receive tissue plasminogen activator have better outcome when statins were taken before stroke. Methods— We evaluated 145 patients with a stroke involving the middle cerebral artery (who received tissue plasminogen activator treatment ( 〈 3 hours). Results— Fifty-eight patients (40%) became functionally independent at 3 months. Factors associated with good outcome were age (68 versus 74.4 years, P 〈 0.001), baseline National Institutes of Health Stroke Scale score (13 versus 18, P 〈 0.001), and proximal middle cerebral artery occlusion (56.1% versus 84.3%, P 〈 0.001). Statins were the only drug taken before stroke that conditioned neurologic outcome. In fact, among patients who were functionally independent, 27.3% were under statins at the time of the index stroke as compared with 13.6% among the group of patients who were dependent or dead by the end of the study period ( P =0.046). A logistic regression model identified baseline National Institutes of Health Stroke Scale score 〈 15 (OR: 5.8, 95% CI: 2.05 to 16.36, P =0.001), age 〈 70 years (OR: 2.93, 95% CI: 1.13 to 7.59, P =0.027), and previous treatment with statins (OR: 5.26, 95% CI: 1.48 to 18.72, P =0.027) as independent predictors of good functional outcome. Conclusions— Patients under statins at the moment of stroke who received thrombolytics had an improved neurologic outcome.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/01.STR.0000258075.58283.8f
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
    detail.hit.zdb_id: 1467823-8
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...