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  • Ovid Technologies (Wolters Kluwer Health)  (20)
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  • Medicine  (20)
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  • Ovid Technologies (Wolters Kluwer Health)  (20)
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  • Medicine  (20)
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  • 1
    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
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467823-8
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  • 2
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 9 ( 2023-09), p. 2241-2250
    Abstract: It is unclear whether patients with different stroke/transient ischemic attack etiologies benefit differently from gene-directed dual antiplatelet therapy. This study explored the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in transient ischemic attack or minor stroke with different causes in the CHANCE-2 trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events-II). METHODS: This was a prespecified analysis of the CHANCE-2 trial, which enrolled 6412 patients with minor stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles. Patients with centralized evaluation of TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification of large-artery atherosclerosis, small-vessel occlusion, and stroke of undetermined cause were included. The primary efficacy outcome was new stroke, and the primary safety outcome was severe or moderate bleeding, both within 90 days. Cox proportional hazards models were used to assess the interaction of TOAST classification with the effects of dual antiplatelet therapy with ticagrelor-aspirin versus clopidogrel-aspirin. RESULTS: A total of 6336 patients were included in this study. In patients administered ticagrelor-aspirin and clopidogrel-aspirin, respectively, stroke recurred in 85 (9.8%) and 88 (10.7%) patients with large-artery atherosclerosis (hazard ratio, 0.86 [95% CI, 0.63–1.18]; P =0.34); 32 (3.6%) and 61 (7.0%) patients with small-vessel occlusion (hazard ratio, 0.51 [95% CI, 0.33–0.79]; P =0.002); and 68 (4.8%) and 87 (5.9%) patients with stroke of undetermined cause (hazard ratio, 0.80 [95% CI, 0.58–1.10]; P =0.17), with P =0.08 for the treatment×cause subtype interaction effect. There were no significant differences in severe or moderate bleeding events in patients with different cause and different treatment. CONCLUSIONS: In this prespecified analysis of the CHANCE-2 trial, the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in preventing new stroke were consistent in patients with different causes. The influence of stroke cause on benefit of gene-guided antiplatelet therapy should be explored by further trials. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04078737.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1467823-8
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  • 3
    In: Journal of Computer Assisted Tomography, Ovid Technologies (Wolters Kluwer Health), Vol. 40, No. 3 ( 2016), p. 402-408
    Type of Medium: Online Resource
    ISSN: 0363-8715
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 2039772-0
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  • 4
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Journal of Computer Assisted Tomography Vol. 46, No. 5 ( 2022-9), p. 800-807
    In: Journal of Computer Assisted Tomography, Ovid Technologies (Wolters Kluwer Health), Vol. 46, No. 5 ( 2022-9), p. 800-807
    Abstract: In this study, we investigate the preoperative and postoperative computed tomography (CT) scores in severe traumatic brain injury (TBI) patients undergoing decompressive craniectomy (DC) and compare their predictive accuracy. Methods Univariate and multivariate logistic regression analyses were used to determine the relationship between CT score (preoperative and postoperative) and mortality at 30 days after injury. The discriminatory power of preoperative and postoperative CT score was assessed by the area under the receiver operating characteristic curve (AUC). Results Multivariate logistic regression analysis adjusted for the established predictors of TBI outcomes showed that preoperative Rotterdam CT score (odds ratio [OR], 3.60; 95% confidence interval [CI] , 1.13–11.50; P = 0.030), postoperative Rotterdam CT score (OR, 4.17; 95% CI, 1.63–10.66; P = 0.003), preoperative Stockholm CT score (OR, 3.41; 95% CI, 1.42–8.18; P = 0.006), postoperative Stockholm CT score (OR, 4.50; 95% CI, 1.60–12.64; P = 0.004), preoperative Helsinki CT score (OR, 1.44; 95% CI, 1.03–2.02; P = 0.031), and postoperative Helsinki CT score (OR, 2.55; 95% CI, 1.32–4.95; P = 0.005) were significantly associated with mortality. The performance of the postoperative Rotterdam CT score was superior to the preoperative Rotterdam CT score (AUC, 0.82–0.97 vs 0.71–0.91). The postoperative Stockholm CT score was superior to the preoperative Stockholm CT score (AUC, 0.76–0.94 vs 0.72–0.92). The postoperative Helsinki CT score was superior to the preoperative Helsinki CT score (AUC, 0.88–0.99 vs 0.65–0.87). Conclusions In conclusion, assessing the CT score before and after DC may be more precise and efficient for predicting early mortality in severe TBI patients who undergo DC.
    Type of Medium: Online Resource
    ISSN: 1532-3145 , 0363-8715
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2039772-0
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  • 5
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 45, No. 9 ( 2014-09), p. 2620-2628
    Abstract: We aimed to develop a risk score (intracerebral hemorrhage–associated pneumonia score, ICH-APS) for predicting hospital-acquired stroke-associated pneumonia (SAP) after ICH. Methods— The ICH-APS was developed based on the China National Stroke Registry (CNSR), in which eligible patients were randomly divided into derivation (60%) and validation (40%) cohorts. Variables routinely collected at presentation were used for predicting SAP after ICH. For testing the added value of hematoma volume measure, we separately developed 2 models with (ICH-APS-B) and without (ICH-APS-A) hematoma volume included. Multivariable logistic regression was performed to identify independent predictors. The area under the receiver operating characteristic curve (AUROC), Hosmer–Lemeshow goodness-of-fit test, and integrated discrimination index were used to assess model discrimination, calibration, and reclassification, respectively. Results— The SAP was 16.4% and 17.7% in the overall derivation (n=2998) and validation (n=2000) cohorts, respectively. A 23-point ICH-APS-A was developed based on a set of predictors and showed good discrimination in the overall derivation (AUROC, 0.75; 95% confidence interval, 0.72–0.77) and validation (AUROC, 0.76; 95% confidence interval, 0.71–0.79) cohorts. The ICH-APS-A was more sensitive for patients with length of stay 〉 48 hours (AUROC, 0.78; 95% confidence interval, 0.75–0.81) than those with length of stay 〈 48 hours (AUROC, 0.64; 95% confidence interval, 0.55–0.73). The ICH-APS-A was well calibrated (Hosmer–Lemeshow test) in the derivation ( P =0.20) and validation ( P =0.66) cohorts. Similarly, a 26-point ICH-APS-B was established. The ICH-APS-A and ICH-APS-B were not significantly different in discrimination and reclassification for SAP after ICH. Conclusion— The ICH-APSs are valid risk scores for predicting SAP after ICH, especially for patients with length of stay 〉 48 hours.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
    detail.hit.zdb_id: 1467823-8
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  • 6
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Circulation Research Vol. 111, No. 7 ( 2012-09-14), p. 837-841
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 111, No. 7 ( 2012-09-14), p. 837-841
    Abstract: Failing cardiomyocytes exhibit decreased efficiency of excitation-contraction (E-C) coupling. The downregulation of junctophilin-2 (JP2), a protein anchoring the sarcoplasmic reticulum to T-tubules, has been identified as a major mechanism underlying the defective E-C coupling. However, the regulatory mechanism of JP2 remains unknown. Objective: To determine whether microRNAs regulate JP2 expression. Methods and Results: Bioinformatic analysis predicted 2 potential binding sites of miR-24 in the 3′-untranslated regions of JP2 mRNA. Luciferase assays confirmed that miR-24 suppressed JP2 expression by binding to either of these sites. In the aortic stenosis model, miR-24 was upregulated in failing cardiomyocytes. Adenovirus-directed overexpression of miR-24 in cardiomyocytes decreased JP2 expression and reduced Ca 2+ transient amplitude and E-C coupling gain. Conclusions: MiR-24–mediated suppression of JP2 expression provides a novel molecular mechanism for E-C coupling regulation in heart cells and suggests a new target against heart failure.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
    detail.hit.zdb_id: 1467838-X
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  • 7
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 88, No. 16_supplement ( 2017-04-18)
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
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  • 8
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 129, No. 9 ( 2021-10-15), p. 825-839
    Abstract: Brain arteriovenous malformations (bAVMs) are abnormal entanglement of blood vessels in brain, with direct connections from arteries to veins, lacking functional capillary bed. Although several somatic mutations were reported, the molecular mechanism and genetic disposition of bAVM remain poorly understood. Objective: We aim to identify transcriptional anomalies and critical functional pathways in bAVM lesions and explore their association with key de novo germline and somatic variants in bAVM patients. Methods and Results: We established a comprehensive bAVM dataset from 269 patients, by performing single-cell sequencing of 17 bAVM lesions, whole-exome sequencing of germline DNA from 60 case-unaffected-parental trios, and genomic/transcriptomic sequencing of 231 bAVM lesions. We found abnormal expression of endothelial and mesenchymal markers in bAVM at both bulk and single-cell level, which was validated by flow cytometric analysis and immunofluorescence staining, suggesting an involvement of endothelial-to-mesenchymal transition (EndMT) process in AVM (arteriovenous-malformation). Using data from the 60 trios, we identified nonsynonymous de novo germline mutations affecting 46 genes, including EXPH5 (detected in 2 independent cases), and vessel-related genes, such as EPAS1 and ENG . Interestingly, knockdown of epas1 in zebrafish embryo showed AVM-like phenotype exclusively in brain. Subsequent computational and experimental analyses demonstrated that expression of genes affected by de novo germline mutations was enriched in vascular cell types and was involved in EndMT-relevant behaviors including cell migration, angiogenesis, and cell marker transition. Moreover, we detected somatic KRAS mutations in 129 of 179 (72%) cases and showed that KRAS mutations were associated with bleeding as the first symptom ( P =0.0072). Following experimental studies demonstrated that KRAS mutations independently regulated EndMT features, consolidating the involvement of EndMT in this disease. Lastly, we showed that lovastatin reversed EndMT features in vitro and ex vivo. Conclusions: Our results suggest the convergent role of de novo germline mutations and somatic mutations in regulating EndMT in bAVM and provided a potential therapeutic option.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467838-X
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  • 9
    In: American Journal of Surgical Pathology, Ovid Technologies (Wolters Kluwer Health), Vol. 40, No. 6 ( 2016-06), p. 836-846
    Abstract: Aggressive natural killer cell leukemia (ANKL) is a rare disease with an extremely aggressive clinical course. The etiology of ANKL is unclear with few genetic/epigenetic aberrations described to date. Moreover, misdiagnosis of ANKL is a frequent problem. Clinicopathologic characteristics of 35 retrospective cases of ANKL were investigated with the aim of improving diagnosis and to find the genetic/epigenetic aberrations associated with ANKL etiology. Because of the relatively low number of leukemic cells in the peripheral blood and bone marrow, diagnosis of ANKL can be missed; therefore, it is important to perform biopsy on solid tissues, if necessary. We describe the pathology of ANKL in the lymph nodes, bone marrow, spleen, liver, and skin, with focus on diagnosis and differentiated diagnosis. We observed young male predominance in our cohort, and the clinical course was more aggressive than reported previously. Low lactate dehydrogenase ( 〈 712 IU/L), chemotherapy or l -asparaginase administration were found to be associated with more favorable outcomes. SH2 domains of STAT5B and STAT3 also were screened for the presence of activating mutations. Moreover, CpG island methylation status of HACE1 , a candidate tumor-suppressor gene, was determined in ANKL samples. We observed activating STAT5B mutations (1/5) and hypermethylation of HACE1 (3/4) in ANKL cases, suggesting that these aberrations may contribute to ANKL pathogenesis.
    Type of Medium: Online Resource
    ISSN: 0147-5185
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 2029143-7
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  • 10
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Cornea Vol. 36, No. 9 ( 2017-09), p. 1133-1138
    In: Cornea, Ovid Technologies (Wolters Kluwer Health), Vol. 36, No. 9 ( 2017-09), p. 1133-1138
    Abstract: To evaluate the efficacy of sodium hyaluronate (HA) eye drops for the treatment of diabetic ocular surface diseases in mice. Methods: Male 6- to 8-week-old C57BL/6 mice underwent induction of type 1 diabetes with intraperitoneal injections of streptozotocin, with normal mice as the control. Topical 0.3% HA, 0.1% HA, 0.4% polyethylene glycol eye drops, and normal saline were administered to diabetic mice with an intact or debrided corneal epithelium. Normal saline was applied in the controls. Corneal epithelial wound healing rate, corneal sensation, nerve fiber density, conjunctival goblet cell number, and MUC-5AC content were measured and compared. Results: Compared with the controls, topical 0.3% HA use in diabetic mice showed significant improvements in the corneal epithelial wound healing rate (48 hours: 91.5% ± 4.8% vs. 79.8% ± 6.1%; P 〈 0.05), corneal sensitivity (4.1 ± 0.3 cm vs. 3.5 ± 0.3 cm; P 〈 0.05), nerve fiber density (12.9% ± 2.3% vs. 6.6% ± 2.4%; P 〈 0.05), conjunctival goblet cell number (31.0 ± 8.4/100 μm vs. 19.6 ± 7.1/100 μm; P 〈 0.05), and MUC-5AC content (12.5 ± 1.4 ng/mg vs. 7.8 ± 1.5 ng/mg protein; P 〈 0.05). The beneficial effects of 0.3% HA were better than those of 0.1% HA and 0.4% polyethylene glycol. Conclusions: Topical 0.3% HA treatment promoted corneal epithelial regeneration, improved corneal sensation, and increased density of corneal nerve fibers and conjunctival goblet cells in mice with diabetic ocular surface diseases.
    Type of Medium: Online Resource
    ISSN: 0277-3740
    RVK:
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2045943-9
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