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  • 1
    In: International Journal of Stroke, SAGE Publications, Vol. 12, No. 4 ( 2017-06), p. 377-382
    Abstract: Numerous neuroprotective drugs have failed to show benefit in the treatment of acute ischemic stroke, making the search for new treatments imperative. Uric acid is an endogenous antioxidant making it a drug candidate to improve stroke outcomes. Aim To report the effects of uric acid therapy in stroke patients receiving intravenous thrombolysis and mechanical thrombectomy. Methods Forty-five patients with proximal vessel occlusions enrolled in the URICO-ICTUS trial received intravenous recombinant tissue plasminogen activator within 4.5 h after stroke onset and randomized to intravenous 1000 mg uric acid or placebo (NCT00860366). These patients also received mechanical thrombectomy because a brain computed tomogaphy angiography confirmed the lack of proximal recanalization at the end of systemic thrombolysis. The primary outcome was good functional outcome at 90 days (modified Rankin Score 0–2). Safety outcomes included mortality, symptomatic intracerebral bleeding, and gout attacks. Results The rate of successful revascularization was 〉 80% in the uric acid and the placebo groups but good functional outcome was observed in 16 out of 24 (67%) patients treated with uric acid and 10 out of 21 (48%) treated with placebo (adjusted Odds Ratio, 6.12 (95% CI 1.08–34.56)). Mortality was observed in two out of 24 (8.3%) patients treated with uric acid and one out of 21 (4.8%) treated with placebo (adjusted Odds Ratio, 3.74 (95% CI 0.06–226.29)). Symptomatic cerebral bleeding and gout attacks were similar in both groups. Conclusions Uric acid therapy was safe and improved stroke outcomes in stroke patients receiving intravenous thrombolysis followed by thrombectomy. Validation of this simple strategy in a larger trial is urgent.
    Type of Medium: Online Resource
    ISSN: 1747-4930 , 1747-4949
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2017
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  • 2
    In: European Stroke Journal, SAGE Publications
    Abstract: Malignant middle cerebral artery infarction (MCI) needs rapid intervention. This study aimed to enhance the prediction of MCI using computed tomography perfusion (CTP) with varied quantitative benchmarks. Materials and Methods: We retrospectively analyzed 253 patients from a single-center registry presenting with acute, severe, proximal large vessel occlusion studied with whole-brain CTP imaging at hospital arrival within the first 24 h of symptoms-onset. MCI was defined by clinical and imaging criteria, including decreased level of consciousness, anisocoria, death due to cerebral edema, or need for decompressive craniectomy, together with midline shift ⩾6 mm, or infarction of more than 50% of the MCA territory. The predictive accuracy of baseline ASPECTS and CTP quantifications for MCI was assessed by receiver operating characteristic (ROC) area under the curve (AUC) while F-score was calculated as an indicator of precision and sensitivity. Results: Sixty-three out of 253 patients (25%) fulfilled MCI criteria and had worse clinical and imaging results than the non-MCI group. The capacity to predict MCI was lower for baseline ASPECTS (AUC 0.83, F-score 0.52, Youden’s index 6), than with perfusion-based measures: relative cerebral blood volume threshold 〈 40% (AUC 0.87, F-score 0.71, Youden’s index 34 mL) or relative cerebral blood flow threshold 〈 35% (AUC 0.87, F-score 0.62, Youden’s index 67 mL). CTP based on rCBV measurements identified twice as many MCI as baseline CT ASPECTS. Discussion and conclusion: CTP-based quantifications may offer enhanced predictive capabilities for MCI compared to non-contrast baseline CT ASPECTS, potentially improving the monitoring of severe ischemic stroke patients at risk of life-threatening edema and its treatment.
    Type of Medium: Online Resource
    ISSN: 2396-9873 , 2396-9881
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2024
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  • 3
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 40, No. 5 ( 2020-05), p. 966-977
    Abstract: Computed tomography perfusion (CTP) allows the estimation of pretreatment ischemic core after acute ischemic stroke. However, CTP-derived ischemic core may overestimate final infarct volume. We aimed to evaluate the accuracy of CTP-derived ischemic core for the prediction of final infarct volume according to time from stroke onset to recanalization in 104 patients achieving complete recanalization after mechanical thrombectomy who had a pretreatment CTP and a 24-h follow-up MRI-DWI. A range of CTP thresholds was explored in perfusion maps at constant increments for ischemic core calculation. Time to recanalization modified significantly the association between ischemic core and DWI lesion in a non-linear fashion ( p-interaction = 0.018). Patients with recanalization before 4.5 h had significantly lower intraclass correlation coefficient (ICC) values between CTP-predicted ischemic core and DWI lesion ( n = 54; best threshold relative cerebral blood flow (rCBF)  〈  25%, ICC = 0.673, 95% CI = 0.495–0.797) than those with later recanalization ( n = 50; best threshold rCBF  〈  30%, ICC = 0.887, 95% CI = 0.811–0.935, p = 0.013), as well as poorer spatial lesion agreement. The significance of the associations between CTP-derived ischemic core and clinical outcome at 90 days was lost in patients recanalized before 4.5 h. CTP-derived ischemic core must be interpreted with caution given its dependency on time to recanalization, primarily in patients with higher chances of early recanalization.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
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  • 4
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications
    Abstract: Hyperglycemia has been linked to worsening outcomes after subarachnoid hemorrhage (SAH). Nevertheless, the mechanisms involved in the pathogenesis of SAH have been scarcely evaluated so far. The role of hyperglycemia was assessed in an experimental model of SAH by T 2 weighted, dynamic contrast-enhanced magnetic resonance imaging (T 2 W and DCE-MRI), [ 18 F]BR-351 PET imaging and immunohistochemistry. Measures included the volume of bleeding, the extent of cerebral infarction and brain edema, blood brain barrier disruption (BBBd), neutrophil infiltration and matrix metalloprotease (MMP) activation. The neurofunctional outcome, neurodegeneration and myelinization were also investigated. The induction of hyperglycemia increased mortality, the size of the ischemic lesion, brain edema, neurodegeneration and worsened neurological outcome during the first 3 days after SAH in rats. In addition, these results show for the first time the exacerbating effect of hyperglycemia on in vivo MMP activation, Intercellular Adhesion Molecule 1 (ICAM-1) expression and neutrophil infiltration together with increased BBBd, bleeding volume and fibrinogen accumulation at days 1 and 3 after SAH. Notably, these data provide valuable insight into the detrimental effect of hyperglycemia on early BBB damage mediated by neutrophil infiltration and MMP activation that could explain the worse prognosis in SAH.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
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  • 5
    In: International Journal of Stroke, SAGE Publications, Vol. 5, No. 4 ( 2010-08), p. 325-328
    Abstract: Oxidative stress is a major contributor to brain damage in patients with ischaemic stroke. Uric acid (UA) is a potent endogenous antioxidant molecule. In experimental ischaemia in rats, the exogenous administration of uric acid is neuroprotective and enhances the effect of rtPA. Moreover, in acute stroke patients receiving rtPA within 3 h of stroke onset, the intravenous administration of uric acid is safe, prevents an early decline in uric acid levels and reduces an early increase in oxidative stress markers and in active matrix metalloproteinase nine levels. Aim To determine whether the combined treatment with uric acid and rtPA is superior to rtPA alone in terms of clinical efficacy in acute ischaemic stroke patients treated within the first 4.5 h of onset of symptoms. Study design Multicentre, interventional, randomised, double-blind and vehicle-controlled efficacy study with parallel assignment (1:1). Estimated enrolment: 420 patients over 3 years, starting in January 2010. Treatment arms included patients will receive a single intravenous infusion of 1 g of UA dissolved in a vehicle (500 ml of 0.1% lithium carbonate and 5% mannitol) ( n = 210) or vehicle alone ( n = 210). Inclusion and exclusion criteria: the study will include patients older than 18 years, treated with rtPA within the first 4.5 h of clinical onset and with a baseline National Institute of Health Stroke Scale score 〉 6 and 〈 25 and a modified Rankin Scale score ≤ 2 before the ischaemic event. Patients with renal insufficiency, gout or asymptomatic hiperuricaemia treated with allopurinol will be excluded. Study outcomes The primary outcome measure is the proportion of patients achieving an modified Rankin Scale of 0 to 1 at 3 months after treatment or two in those patients with a prior qualifying modified Rankin Scale of 2. Secondary outcome measures include the final infarction volume measured at 72 h and the proportion of patients with symptomatic intracranial haemorrhage (≥ 4 points of increase in the National Institute of Health Stroke Scale score).
    Type of Medium: Online Resource
    ISSN: 1747-4930 , 1747-4949
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2010
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  • 6
    In: The International Journal of Biological Markers, SAGE Publications, Vol. 29, No. 4 ( 2014-10), p. 363-371
    Abstract: The highly conserved mini-chromosome maintenance proteins (MCM) are important in the initiation of DNA replication. Few studies have correlated MCM expression with the progression of cancer. Objectives (i) To analyze the expression of MCM2 in cervical cancer; (ii) to correlate MCM2 expression with the clinical tumor staging according to FIGO classification, and (iii) to relate HPV type to MCM2 expression. Methods Tissue micro-arrays (TMA) from patients with invasive cervical cancer and controls were analyzed. Human papillomavirus (HPV) DNA detection and HPV types were determined by in situ hybridization, PCR, and sequencing. MCM2 expression was analyzed by immunohistochemistry. Results The most prevalent HPV types found in invasive cancer were HPV 16 (66.6%), followed by HPV 33 (11.8%), and HPV 35 (3.6%). An increased (p 〈 0.05) expression of MCM2 was found in invasive cervical cancers compared to controls. Moreover, a strong correlation was found between the MCM2-positive cells and the presence of HPV DNA detected by in situ hybridization. No statistically significant difference was observed between MCM2 expression and FIGO stage. Conclusions The present study shows that HPV-infected cells strongly express MCM2; nevertheless, our data suggests that MCM2 is not a good biomarker when comparing the different clinical stages of cervical cancer.
    Type of Medium: Online Resource
    ISSN: 1724-6008 , 1724-6008
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2014
    detail.hit.zdb_id: 1475778-3
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  • 7
    In: International Journal of Stroke, SAGE Publications, Vol. 16, No. 1 ( 2021-01), p. 110-116
    Abstract: The potential value of rescue intraarterial thrombolysis in patients with large vessel occlusion stroke treated with mechanical thrombectomy has not been assessed in randomized trials. Aim The CHemical OptImization of Cerebral Embolectomy trial aims to establish whether rescue intraarterial thrombolysis is more effective than placebo in improving suboptimal reperfusion scores in patients with large vessel occlusion stroke treated with mechanical thrombectomy. Sample size estimates A sample size of 200 patients allocated 1:1 to intraarterial thrombolysis or intraarterial placebo will have 〉 95% statistical power for achieving the primary outcome (5% in the control versus 60% in the treatment group) for a two-sided (5% alpha, and 5% lost to follow-up). Methods and design We conducted a multicenter, randomized, placebo-controlled, double blind, phase 2b trial. Eligible patients are 18 or older with symptomatic large vessel occlusion treated with mechanical thrombectomy resulting in a modified treatment in cerebral ischemia score 2b at end of the procedure. Patients will receive 20–30 min intraarterial infusion of recombinant tissue plasminogen activator or placebo (0.5 mg/ml, maximum dose limit 22.5 mg). Study outcome(s) The primary outcome is the proportion of patients with an improved modified treatment in cerebral ischemia score 10 min after the end of the study treatment. Secondary outcomes include the shift analysis of the modified Rankin Scale, the infarct expansion ratio, the proportion of excellent outcome (modified Rankin Scale 0–1), the proportion of infarct expansion, and the infarction volume. Mortality and symptomatic intracerebral bleeding will be assessed. Discussion The study will provide evidence whether rescue intraarterial thrombolysis improves brain reperfusion in patients with large vessel occlusion stroke and incomplete reperfusion (modified treatment in cerebral ischemia 2b) at the end of mechanical thrombectomy.
    Type of Medium: Online Resource
    ISSN: 1747-4930 , 1747-4949
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
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  • 8
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 37, No. 1 ( 2017-01), p. 153-165
    Abstract: Endovascular reperfusion therapy is increasingly used for acute ischemic stroke treatment. The occurrence of parenchymal hemorrhage is clinically relevant and increases with reperfusion therapies. Herein we aimed to examine the optimal perfusion CT-derived parameters and the impact of the duration of brain ischemia for the prediction of parenchymal hemorrhage after endovascular therapy. A cohort of 146 consecutive patients with anterior circulation occlusions and treated with endovascular reperfusion therapy was analyzed. Recanalization was assessed at the end of reperfusion treatment, and the rate of parenchymal hemorrhage at follow-up neuroimaging. In regression analyses, cerebral blood volume and cerebral blood flow performed better than Delay Time maps for the prediction of parenchymal hemorrhage. The most informative thresholds (receiver operating curves) for relative cerebral blood volume and relative cerebral blood flow were values lower than 2.5% of normal brain. In binary regression analyses, the volume of regions with reduced relative cerebral blood volume and/or relative cerebral blood flow was significantly associated with an increased risk of parenchymal hemorrhage, as well as delayed vessel recanalization. These results highlight the relevance of the severity and duration of ischemia as drivers of blood-brain barrier disruption in acute ischemic stroke and support the role of perfusion CT for the prediction of parenchymal hemorrhage.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2017
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  • 9
    Online Resource
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    SAGE Publications ; 2007
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 27, No. 1 ( 2007-01), p. 14-20
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 27, No. 1 ( 2007-01), p. 14-20
    Abstract: Uric acid is a natural antioxidant that protects the brain in a model of transient focal ischemia in rats. Here we sought to investigate whether uric acid was protective in a model of thromboembolic brain ischemia in rats, and whether the global benefit of recombinant tissue plasminogen activator (rt-PA) was improved by the combined treatment. Adult male Sprague-Dawley rats underwent either ischemia by thromboembolic middle cerebral artery occlusion (MCAO) or sham operation. Uric acid (16 mg/kg) was injected intravenously (i.v.). 20 mins after mCaO, whereas rt-PA (10 mg/kg) was administered i.v. at 3 h. A group of rats received the combined treatment. Rats underwent two neurologic examinations (30 mins and 24 h after MCAO). At 24 h, infarct volume was measured and brain neutrophil infiltration and protein tyrosine nitration were assessed. Treatment with either uric acid or rt-PA reduced infarct volume versus controls ( P 〈 0.05). The protective effect against brain ischemia was greater after cotreatment of uric acid with rt-PA ( P 〈 0.001), which added further benefit to rt-PA alone ( P 〈 0.05). The neurologic score worsened during the first 24 h in treatment controls, whereas it improved in rats receiving uric acid and/or rt-PA. Uric acid strongly reduced ischemia-induced tyrosine nitration, but it was more effective alone than combined with rt-PA, suggesting that reperfusion enhances nitrotyrosine formation. All treatments reduced postischemic brain neutrophil infiltration. These results show that uric acid administered early after thromboembolic stroke is neuroprotective in the rat brain, as it reduces infarct volume, ameliorates the neurologic function, attenuates the inflammatory response, and extends the benefits of rt-PA.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2007
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  • 10
    In: European Stroke Journal, SAGE Publications
    Abstract: Stroke Units (SU) have been suggested as an alternative to Intensive Care units (ICU) for initial admission of low-grade non-aneurysmal spontaneous subarachnoid haemorrhage (naSAH). We hypothesised that the incidence of in-hospital complications and long-term clinical outcomes in low-grade naSAH patients would be comparable in both settings, and that a cost-minimisation analysis would favour the use of SU. Patients and methods: Retrospective, single-centre study at a third-level stroke-referral hospital, including low-grade spontaneous naSAH patients with WFNS 1–2. Primary outcomes were death and functional status at 3 months. Secondary outcomes were incidence of in-hospital major neurological and systemic complications. Additionally, a cost-minimisation analysis was conducted to estimate the average cost savings that could be achieved with the most efficient approach. Results: Out of 96 naSAH patients, 30 (31%) were initially admitted to ICU and 66 (69%) to SU. Both groups had similar demographic and radiological features except for a higher proportion of WFNS 2 in ICU subgroup. There were no statistically significant differences between ICU and SU-managed subgroups in death rate (2 (7%) and 1 (2%), respectively), functional outcome at 90 days (28 (93%) and 61 (92%) modified Rankin Scale 0–2) or neurological and systemic in-hospital complications. Cost-minimisation analysis demonstrated significant monetary savings favouring the SU strategy. Discussion and conclusion: Initial admission to the SU appears to be a safe and cost-effective alternative to the ICU for low-grade naSAH patients, with comparable clinical outcomes and a reduction of hospitalisation-related costs. Prospective multicenter randomised studies are encouraged to further evaluate this approach.
    Type of Medium: Online Resource
    ISSN: 2396-9873 , 2396-9881
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
    detail.hit.zdb_id: 2851287-X
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