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  • Ovid Technologies (Wolters Kluwer Health)  (12)
  • 1
    Online Resource
    Online Resource
    Workflows and Outcomes in Patients With Suspected Large Vessel Occlusion Stroke Triaged in Urban and Nonurban Areas
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Stroke Vol. 53, No. 12 ( 2022-12), p. 3728-3740
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 12 ( 2022-12), p. 3728-3740
    Abstract: We aim to compare the outcome of patients from urban areas, where the referral center is able to perform thrombectomy, with patients from nonurban areas enrolled in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion). Methods: Patients with suspected large vessel occlusion stroke, as evaluated by a Rapid Arterial Occlusion Evaluation score of ≥5, from urban catchment areas of thrombectomy-capable centers during RACECAT trial enrollment period were included in the Stroke Code Registry of Catalonia. Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with an ischemic stroke. Secondary outcomes included mortality at 90 days, rate of thrombolysis and thrombectomy, time from onset to thrombolysis, and thrombectomy initiation. Propensity score matching was used to assemble a cohort of patients with similar characteristics. Results: The analysis included 1369 patients from nonurban areas and 2502 patients from urban areas. We matched 920 patients with an ischemic stroke from urban areas and nonurban areas based on their propensity scores. Patients with ischemic stroke from nonurban areas had higher degrees of disability at 90 days (median [interquartle range] modified Rankin Scale score, 3 [2–5] versus 3 [1–5], common odds ratio, 1.25 [95% CI, 1.06–1.48] ); the observed average effect was only significant in patients with large vessel stroke (common odds ratio, 1.36 [95% CI, 1.08–1.65]). Mortality rate was similar between groups(odds ratio, 1.02 [95% CI, 0.81–1.28] ). Patients from nonurban areas had higher odds of receiving thrombolysis (odds ratio, 1.36 [95% CI, 1.16–1.67]), lower odds of receiving thrombectomy(odds ratio, 0.61 [95% CI, 0.51–0.75] ), and longer time from stroke onset to thrombolysis (mean difference 38 minutes [95% CI, 25–52]) and thrombectomy(mean difference 66 minutes [95% CI, 37–95] ). Conclusions: In Catalonia, Spain, patients with large vessel occlusion stroke triaged in nonurban areas had worse neurological outcomes than patients from urban areas, where the referral center was able to perform thrombectomy. Interventions aimed at improving organizational practices and the development of thrombectomy capabilities in centers located in remote areas should be pursued. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02795962.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.122.040768
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467823-8
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  • 2
    Online Resource
    Online Resource
    Association of Time of Day With Outcomes Among Patients Triaged for a Suspected Severe Stroke in Nonurban Catalonia
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Stroke Vol. 54, No. 3 ( 2023-03), p. 770-780
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 3 ( 2023-03), p. 770-780
    Abstract: We aim to assess whether time of day modified the treatment effect in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion Trial), a cluster-randomized trial that did not demonstrate the benefit of direct transportation to a thrombectomy-capable center versus nearest local stroke center for patients with a suspected large vessel stroke triaged in nonurban Catalonia between March 2017 and June 2020. Methods: We performed a post hoc analysis of RACECAT to evaluate if the association between initial transport routing and functional outcome differed according to trial enrollment time: daytime (8:00 am –8:59 pm ) and nighttime (9:00 pm –7:59 am ). Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with ischemic stroke. Subgroup analyses according to stroke subtype were evaluated. Results: We included 949 patients with an ischemic stroke, of whom 258 patients(27%) were enrolled during nighttime. Among patients enrolled during nighttime, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days (adjusted common odds ratio [acOR] , 1.620 [95% CI, 1.020–2.551]); no significant difference between trial groups was present during daytime (acOR, 0.890 [95% CI, 0.680–1.163] ; P interaction =0.014). Influence of nighttime on the treatment effect was only evident in patients with large vessel occlusion(daytime, acOR 0.766 [95% CI, 0.548–1.072]; nighttime, acOR, 1.785 [95% CI, 1.024–3.112] ; P interaction 〈 0.01); no heterogeneity was observed for other stroke subtypes ( P interaction 〉 0.1 for all comparisons). We observed longer delays in alteplase administration, interhospital transfers, and mechanical thrombectomy initiation during nighttime in patients allocated to local stroke centers. Conclusions: Among patients evaluated during nighttime for a suspected acute severe stroke in non-urban areas of Catalonia, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days. This association was only evident in patients with confirmed large vessel occlusion on vascular imaging. Time delays in alteplase administration and interhospital transfers might mediate the observed differences in clinical outcome. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02795962.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.122.041013
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1467823-8
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  • 3
    Online Resource
    Online Resource
    Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease : Results From the CREDENCE Trial and Meta-Analysis
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Stroke Vol. 52, No. 5 ( 2021-05), p. 1545-1556
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 5 ( 2021-05), p. 1545-1556
    Abstract: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. Methods: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis. Results: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55–1.08] ). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61–1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19–1.32] ; n=18), and undetermined (HR, 0.54 [95% CI, 0.20–1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53–1.10] ; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HR pooled , 0.96 [95% CI, 0.82–1.12]), ischemic stroke (HR pooled , 1.01 [95% CI, 0.89–1.14]), hemorrhagic stroke (HR pooled , 0.50 [95% CI, 0.30–0.83]), undetermined stroke (HR pooled , 0.86 [95% CI, 0.49–1.51]), and AF/AFL (HR pooled , 0.81 [95% CI, 0.71–0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate ( P =0.01), with protection in the lowest estimated glomerular filtration rate ( 〈 45 mL/min/1.73 m 2 ]) subgroup (HR pooled , 0.50 [95% CI, 0.31–0.79]). Conclusions: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02065791.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.120.031623
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467823-8
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  • 4
    Online Resource
    Online Resource
    Quantitative Signal Intensity in Fluid-Attenuated Inversion Recovery and Treatment Effect in the WAKE-UP Trial
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Stroke Vol. 51, No. 1 ( 2020-01), p. 209-215
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 51, No. 1 ( 2020-01), p. 209-215
    Abstract: Relative signal intensity of acute ischemic stroke lesions in fluid-attenuated inversion recovery (fluid-attenuated inversion recovery relative signal intensity [FLAIR-rSI]) magnetic resonance imaging is associated with time elapsed since stroke onset with higher intensities signifying longer time intervals. In the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke Trial), intravenous alteplase was effective in patients with unknown onset stroke selected by visual assessment of diffusion weighted imaging fluid-attenuated inversion recovery mismatch, that is, in those with no marked fluid-attenuated inversion recovery hyperintensity in the region of the acute diffusion weighted imaging lesion. In this post hoc analysis, we investigated whether quantitatively measured FLAIR-rSI modifies treatment effect of intravenous alteplase. Methods— FLAIR-rSI of stroke lesions was measured relative to signal intensity in a mirrored region in the contralesional hemisphere. The relationship between FLAIR-rSI and treatment effect on functional outcome assessed by the modified Rankin Scale (mRS) after 90 days was analyzed by binary logistic regression using different end points, that is, favorable outcome defined as mRS score of 0 to 1, independent outcome defined as mRS score of 0 to 2, ordinal analysis of mRS scores (shift analysis). All models were adjusted for National Institutes of Health Stroke Scale at symptom onset and stroke lesion volume. Results— FLAIR-rSI was successfully quantified in stroke lesions in 433 patients (86% of 503 patients included in WAKE-UP). Mean FLAIR-rSI was 1.06 (SD, 0.09). Interaction of FLAIR-rSI and treatment effect was not significant for mRS score of 0 to 1 ( P =0.169) and shift analysis ( P =0.086) but reached significance for mRS score of 0 to 2 ( P =0.004). We observed a smooth continuing trend of decreasing treatment effects in relation to clinical end points with increasing FLAIR-rSI. Conclusions— In patients in whom no marked parenchymal fluid-attenuated inversion recovery hyperintensity was detected by visual judgement in the WAKE-UP trial, higher FLAIR-rSI of diffusion weighted imaging lesions was associated with decreased treatment effects of intravenous thrombolysis. This parallels the known association of treatment effect and elapsing time of stroke onset.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.119.027390
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1467823-8
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  • 5
    Online Resource
    Online Resource
    Epigenetic Signatures of Cigarette Smoking
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Circulation: Cardiovascular Genetics Vol. 9, No. 5 ( 2016-10), p. 436-447
    Details
    In: Circulation: Cardiovascular Genetics, Ovid Technologies (Wolters Kluwer Health), Vol. 9, No. 5 ( 2016-10), p. 436-447
    Abstract: DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders. Methods and Results— To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15 907 blood-derived DNA samples from participants in 16 cohorts (including 2433 current, 6518 former, and 6956 never smokers). Comparing current versus never smokers, 2623 cytosine–phosphate–guanine sites (CpGs), annotated to 1405 genes, were statistically significantly differentially methylated at Bonferroni threshold of P 〈 1×10 −7 (18 760 CpGs at false discovery rate 〈 0.05). Genes annotated to these CpGs were enriched for associations with several smoking-related traits in genome-wide studies including pulmonary function, cancers, inflammatory diseases, and heart disease. Comparing former versus never smokers, 185 of the CpGs that differed between current and never smokers were significant P 〈 1×10 −7 (2623 CpGs at false discovery rate 〈 0.05), indicating a pattern of persistent altered methylation, with attenuation, after smoking cessation. Transcriptomic integration identified effects on gene expression at many differentially methylated CpGs. Conclusions— Cigarette smoking has a broad impact on genome-wide methylation that, at many loci, persists many years after smoking cessation. Many of the differentially methylated genes were novel genes with respect to biological effects of smoking and might represent therapeutic targets for prevention or treatment of tobacco-related diseases. Methylation at these sites could also serve as sensitive and stable biomarkers of lifetime exposure to tobacco smoke.
    Type of Medium: Online Resource
    ISSN: 1942-325X , 1942-3268
    URL: Article
    DOI: 10.1161/CIRCGENETICS.116.001506
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 2927603-2
    detail.hit.zdb_id: 2457085-0
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  • 6
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    Online Resource
    Loss of Nuclear Envelope Integrity and Increased Oxidant Production Cause DNA Damage in Adult Hearts Deficient in PKP2: A Molecular Substrate of ARVC
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Circulation Vol. 146, No. 11 ( 2022-09-13), p. 851-867
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 146, No. 11 ( 2022-09-13), p. 851-867
    Abstract: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by high propensity to life-threatening arrhythmias and progressive loss of heart muscle. More than 40% of reported genetic variants linked to ARVC reside in the PKP2 gene, which encodes the PKP2 protein (plakophilin-2). Methods: We describe a comprehensive characterization of the ARVC molecular landscape as determined by high-resolution mass spectrometry, RNA sequencing, and transmission electron microscopy of right ventricular biopsy samples obtained from patients with ARVC with PKP2 mutations and left ventricular ejection fraction 〉 45%. Samples from healthy relatives served as controls. The observations led to experimental work using multiple imaging and biochemical techniques in mice with a cardiac-specific deletion of Pkp2 studied at a time of preserved left ventricular ejection fraction and in human induced pluripotent stem cell–derived PKP2-deficient myocytes. Results: Samples from patients with ARVC present a loss of nuclear envelope integrity, molecular signatures indicative of increased DNA damage, and a deficit in transcripts coding for proteins in the electron transport chain. Mice with a cardiac-specific deletion of Pkp2 also present a loss of nuclear envelope integrity, which leads to DNA damage and subsequent excess oxidant production (O 2 .– and H 2 O 2 ), the latter increased further under mechanical stress (isoproterenol or exercise). Increased oxidant production and DNA damage is recapitulated in human induced pluripotent stem cell–derived PKP2-deficient myocytes. Furthermore, PKP2-deficient cells release H 2 O 2 into the extracellular environment, causing DNA damage and increased oxidant production in neighboring myocytes in a paracrine manner. Treatment with honokiol increases SIRT3 (mitochondrial nicotinamide adenine dinucleotide–dependent protein deacetylase sirtuin-3) activity, reduces oxidant levels and DNA damage in vitro and in vivo, reduces collagen abundance in the right ventricular free wall, and has a protective effect on right ventricular function. Conclusions: Loss of nuclear envelope integrity and subsequent DNA damage is a key substrate in the molecular pathology of ARVC. We show transcriptional downregulation of proteins of the electron transcript chain as an early event in the molecular pathophysiology of the disease (before loss of left ventricular ejection fraction 〈 45%), which associates with increased oxidant production (O 2 .– and H 2 O 2 ). We propose therapies that limit oxidant formation as a possible intervention to restrict DNA damage in ARVC.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.122.060454
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1466401-X
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  • 7
    Online Resource
    Online Resource
    Nosocomial Rotavirus Gastroenteritis in Spain : A Multicenter Prospective Study
    Ovid Technologies (Wolters Kluwer Health) ; 2010
    In:  Pediatric Infectious Disease Journal Vol. 29, No. 1 ( 2010-01), p. 23-27
    Details
    In: Pediatric Infectious Disease Journal, Ovid Technologies (Wolters Kluwer Health), Vol. 29, No. 1 ( 2010-01), p. 23-27
    Type of Medium: Online Resource
    ISSN: 0891-3668
    URL: Article
    DOI: 10.1097/INF.0b013e3181b3603a
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2010
    detail.hit.zdb_id: 2020216-7
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  • 8
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    Online Resource
    Pharmacological Modulation of Neutrophil Extracellular Traps Reverses Thrombotic Stroke tPA (Tissue-Type Plasminogen Activator) Resistance
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Stroke Vol. 50, No. 11 ( 2019-11), p. 3228-3237
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 50, No. 11 ( 2019-11), p. 3228-3237
    Abstract: Recanalization of the occluded artery is a primary goal in stroke treatment. Unfortunately, endovascular treatment is not always available, and tPA (tissue-type plasminogen activator) therapy is limited by its narrow therapeutic window; importantly, the rate of early arterial recanalization after tPA administration is low, especially for platelet-rich thrombi. The mechanisms for this tPA resistance are not well known. Since neutrophil extracellular traps (NETs) have been implicated in this setting, our aim was to study whether NET pharmacological modulation can reverse tPA resistance and the role of TLR4 (Toll-like receptor 4), previously related to NET formation, in thrombosis. Methods— To this goal, we have used a mouse photothrombotic stroke model, which produces a fibrin-free thrombus composed primarily of aggregated platelets and thrombi obtained from human stroke patients. Results— Our results demonstrate that (1) administration of DNase-I, which promotes NETs lysis, but not of tPA, recanalizes the occluded vessel improving photothrombotic stroke outcome; (2) a preventive treatment with Cl-amidine, impeding NET formation, completely precludes thrombotic occlusion; (3) platelet TLR4 mediates NET formation after photothrombotic stroke; and (4) ex vivo fresh platelet-rich thrombi from ischemic stroke patients are effectively lysed by DNase-I. Conclusions— Hence, our data open new avenues for recanalization of platelet-rich thrombi after stroke, especially to overcome tPA resistance.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.119.026848
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 1467823-8
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  • 9
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    Online Resource
    Clinicopathological Study of Regressed Testicular Tumors (Apparent Extragonadal Germ Cell Neoplasms)
    Ovid Technologies (Wolters Kluwer Health) ; 2009
    In:  Journal of Urology Vol. 182, No. 5 ( 2009-11), p. 2303-2310
    Details
    In: Journal of Urology, Ovid Technologies (Wolters Kluwer Health), Vol. 182, No. 5 ( 2009-11), p. 2303-2310
    Type of Medium: Online Resource
    ISSN: 0022-5347 , 1527-3792
    URL: Article
    DOI: 10.1016/j.juro.2009.07.045
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2009
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  • 10
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    Online Resource
    Osteoblasts in HIV-infected patients: HIV-1 infection and cell function
    Ovid Technologies (Wolters Kluwer Health) ; 2001
    In:  AIDS Vol. 15, No. 17 ( 2001-11), p. 2239-2243
    Details
    In: AIDS, Ovid Technologies (Wolters Kluwer Health), Vol. 15, No. 17 ( 2001-11), p. 2239-2243
    Type of Medium: Online Resource
    ISSN: 0269-9370
    URL: Article
    DOI: 10.1097/00002030-200111230-00004
    RVK:
    XA 16838
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2001
    detail.hit.zdb_id: 2012212-3
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