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  • Ovid Technologies (Wolters Kluwer Health)  (27)
  • 1
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 146, No. 9 ( 2022-08-30), p. 657-672
    Abstract: Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain. Methods: The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin therapy. Primary outcome was major adverse cardiovascular events (MACE; coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, hospitalization for unstable angina). Associations between baseline apoB or apoB at 4 months and MACE were assessed in adjusted Cox proportional hazards and propensity score–matched models. Results: Median follow-up was 2.8 years. In proportional hazards analysis in the placebo group, MACE incidence increased across increasing baseline apoB strata (3.2 [95% CI, 2.9–3.6], 4.0 [95% CI, 3.6–4.5] , and 5.5 [95% CI, 5.0–6.1] events per 100 patient-years in strata 〈 75, 75– 〈 90, ≥90 mg/dL, respectively; P trend 〈 0.0001) and after adjustment for low-density lipoprotein cholesterol ( P trend =0.035). Higher baseline apoB stratum was associated with greater relative ( P trend 〈 0.0001) and absolute reduction in MACE with alirocumab versus placebo. In the alirocumab group, the incidence of MACE after month 4 decreased monotonically across decreasing achieved apoB strata (4.26 [95% CI, 3.78–4.79], 3.09 [95% CI, 2.69–3.54] , and 2.41 [95% CI, 2.11–2.76] events per 100 patient-years in strata ≥50, 〉 35– 〈 50, and ≤35 mg/dL, respectively). Compared with propensity score–matched patients from the placebo group, treatment hazard ratios for alirocumab also decreased monotonically across achieved apoB strata. Achieved apoB was predictive of MACE after adjustment for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol but not vice versa. Conclusions: In patients with recent acute coronary syndrome and elevated atherogenic lipoproteins, MACE increased across baseline apoB strata. Alirocumab reduced MACE across all strata of baseline apoB, with larger absolute reductions in patients with higher baseline levels. Lower achieved apoB was associated with lower risk of MACE, even after accounting for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol, indicating that apoB provides incremental information. Achievement of apoB levels as low as ≤35 mg/dL may reduce lipoprotein-attributable residual risk after acute coronary syndrome. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01663402.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1466401-X
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  • 2
    In: Journal of Urology, Ovid Technologies (Wolters Kluwer Health), Vol. 201, No. Supplement 4 ( 2019-04)
    Type of Medium: Online Resource
    ISSN: 0022-5347 , 1527-3792
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
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  • 3
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 1996
    In:  Annals of Surgery Vol. 224, No. 1 ( 1996-07), p. 37-42
    In: Annals of Surgery, Ovid Technologies (Wolters Kluwer Health), Vol. 224, No. 1 ( 1996-07), p. 37-42
    Type of Medium: Online Resource
    ISSN: 0003-4932
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1996
    detail.hit.zdb_id: 2002200-1
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  • 4
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 50, No. 11 ( 2019-11), p. 3077-3084
    Abstract: Ischemic stroke causes major disability as a consequence of neuronal loss and recurrent ischemic events. Biomarkers predicting tissue damage or stroke recurrence might be useful to guide an individualized stroke therapy. NfL (neurofilament light chain) is a promising biomarker that might be used for this purpose. Methods— We used individual data of patients with an acute ischemic stroke and clinical long term follow-up. Serum NfL (sNfL) was quantified within 24 hours after admission and after 1 year and compared with other biomarkers (GDF15 [growth differentiation factor 15], S100, NT-proBNP [N-terminal pro-B-type natriuretic peptide] , ANP [atrial natriuretic peptide], and FABP [fatty acid–binding protein] ). The primary end point was functional outcome after 90 days and cerebrovascular events and death (combined cardiovascular end point) within 36 months of follow-up. Results— Two hundred eleven patients (mean age, 68.7 years; SD, ±12.6; 41.2% women) with median clinical severity on the National Institutes of Health Stroke Scale (NIHSS) score of 3 (interquartile range, 1–5) and long-term follow-up with a median of 41.8 months (interquartile range, 40.0–44.5) were prospectively included. We observed a significant correlation between sNfL and NIHSS at hospital admission (r=0.234; P 〈 0.001). sNfL levels increased with the grade of age-related white matter changes ( P 〈 0.001) and were able to predict unfavorable clinical outcome (modified Rankin Scale score, ≥2) 90 days after stroke (odds ratio [OR], 1.562; 95% CI, 1.003–2.433; P =0.048) together with NIHSS (OR, 1.303; 95% CI, 1.164–1.458; P 〈 0.001) and age-related white matter change rating (severe; OR, 3.326; 95% CI, 1.186–9.326; P =0.022). Similarly, sNfL was valuable for the prediction of the combined cardiovascular end point (OR, 2.002; 95% CI, 1.213–3.302; P =0.007), besides NIHSS (OR, 1.110; 95% CI, 1.000–1.232; P =0.049), diabetes mellitus (OR, 2.942; 95% CI, 1.306–6.630; P =0.005), and age-related white matter change rating (severe; OR, 4.816; 95% CI, 1.206–19.229; P =0.026) after multivariate regression analysis. Kaplan-Meier analysis revealed significantly more combined cardiovascular end points (18 [14.1%] versus 38 [45.8%] , log-rank test P 〈 0.001) during long-term follow-up in patients with elevated sNfL levels. Conclusions— sNFL is a valuable biomarker for functional independence 90 days after ischemic stroke and predicts cardiovascular long-term outcome. Clinical Trial Registration— URL: http://www.isrctn.com . Unique identifier: ISRCTN 46104198.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 1467823-8
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  • 5
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 45, No. 6 ( 2014-06), p. 1799-1806
    Abstract: T lymphocytes have recently been identified as key mediators of tissue damage in ischemic stroke. The interaction between very late antigen-4 (VLA-4) and vascular adhesion molecule-1 is crucial for the transvascular egress of T lymphocytes, and inhibition of this interaction by specific antibodies is a powerful strategy to combat autoimmune neuroinflammation. However, whether pharmacological blocking of T-lymphocyte trafficking is also protective during brain ischemia is still unclear. We investigated the efficacy of a monoclonal antibody directed against VLA-4 in mouse models of ischemic stroke. Methods— Transient and permanent middle cerebral artery occlusion was induced in male C57Bl/6 mice. Animals treated with a monoclonal anti-CD49d antibody (300 μg) 24 hours before or 3 hours after the onset of cerebral ischemia and stroke outcome, including infarct size, functional status, and mortality, were assessed between day 1 and day 7. The numbers of immune cells invading the ischemic brain were determined by immunocytochemistry and flow cytometry. Results— Blocking of VLA-4 significantly reduced the invasion of T lymphocytes and neutrophils on day 5 after middle cerebral artery occlusion and inhibited the upregulation of vascular adhesion molecule-1. However, the anti-CD49d antibody failed to influence stroke outcome positively irrespective of the model or the time point investigated. Conclusions— Pharmacological inhibition of the VLA-4/vascular adhesion molecule-1 axis in experimental stroke was ineffective in our hands. Our results cast doubt on the effectiveness of anti-CD49d as a stroke treatment. Further translational studies should be performed before testing anti–VLA-4 antibodies in patients with stroke.
    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
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 45, No. 11 ( 2014-11), p. 3395-3402
    Abstract: Brain injury during stroke results in oxidative stress and the release of factors that include extracellular Ca 2+ , hydrogen peroxide, adenosine diphosphate ribose, and nicotinic acid adenine dinucleotide phosphate. These alterations of the extracellular milieu change the activity of transient receptor potential melastatin subfamily member 2 (TRPM2), a nonselective cation channel expressed in the central nervous system and the immune system. Our goal was to evaluate the contribution of TRPM2 to the tissue damage after stroke. Methods— In accordance with current quality guidelines, we independently characterized Trpm2 in a murine ischemic stroke model in 2 different laboratories. Results— Gene deficiency of Trpm2 resulted in significantly improved neurological outcome and decreased infarct size. Besides an already known moderate neuroprotective effect of Trpm2 deficiency in vitro, ischemic brain invasion by neutrophils and macrophages was particularly reduced in Trpm2 -deficient mice. Bone marrow chimeric mice revealed that Trpm2 deficiency in the peripheral immune system is responsible for the protective phenotype. Furthermore, experiments with mixed bone marrow chimeras demonstrated that Trpm2 is essential for the migration of neutrophils and, to a lesser extent, also of macrophages into ischemic hemispheres. Notably, the pharmacological TRPM2 inhibitor, N-(p-amylcinnamoyl)anthranilic acid, was equally protective in the stroke model. Conclusions— Although a neuroprotective effect of TRPM2 in vitro is well known, we can show for the first time that the detrimental role of TRPM2 in stroke primarily depends on its role in activating peripheral immune cells. Targeting TRPM2 systemically represents a promising therapeutic approach for ischemic stroke.
    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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  • 7
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Neurology - Neuroimmunology Neuroinflammation Vol. 9, No. 1 ( 2022-01), p. e1102-
    In: Neurology - Neuroimmunology Neuroinflammation, Ovid Technologies (Wolters Kluwer Health), Vol. 9, No. 1 ( 2022-01), p. e1102-
    Abstract: Adapted ketogenic diet (AKD) and caloric restriction (CR) have been suggested as alternative therapeutic strategies for multiple sclerosis (MS), but information on their impact on neuroaxonal damage is lacking. Thus, we explored the impact of diets on serum neurofilament light chain (sNfL) levels in patients with relapsing-remitting MS. Methods We retrospectively evaluated a prospective randomized controlled trial of 60 patients with MS who were on a common diet or ketogenic diet or fasting. We examined sNfL levels of 40 participants at baseline and at the end of the study after 6 months using single molecule array assay. Results sNfL levels were investigated in 9 controls, 14 participants on CR, and 17 participants on AKD. Correlation analysis showed an association of sNfL with age and disease duration; an association was also found between sNfL and the Multiple Sclerosis Functional Composite. AKD significantly reduced sNfL levels at 6 months compared with the common diet group ( p = 0.001). Discussion For clinical or study use, consider that AKD may incline sNfL levels independent of relapse activity up to 3 months after initiation. At 6 months, AKD, which complements current therapies, reduced sNfL levels, therefore suggesting potential neuroprotective effects in MS. A single cycle of seven-day fasting did not affect sNfL. AKD may be an addition to the armamentarium to help clinicians support patients with MS in a personalized manner with tailored diet strategies. Trial Registration Information Clinical trial registration number NCT01538355 .
    Type of Medium: Online Resource
    ISSN: 2332-7812
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2767740-0
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  • 8
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Neurology - Neuroimmunology Neuroinflammation Vol. 5, No. 5 ( 2018-09), p. e481-
    In: Neurology - Neuroimmunology Neuroinflammation, Ovid Technologies (Wolters Kluwer Health), Vol. 5, No. 5 ( 2018-09), p. e481-
    Abstract: To describe a case of glial fibrillary acidic protein (GFAP)α immunoglobulin G (IgG)-associated encephalitis in a patient referred to us with MS on daclizumab treatment and to summarize characteristics of 5 additional recent German MS cases of serious encephalitis along with a previously published American case of CNS vasculitis associated with daclizumab. Methods Evaluation of cause, clinical symptoms, and treatment response. Results The 6 patients included 4 women and 2 men. The median age at onset was 38 years (range 32–51 years). Clinical presentation was marked by progressing neuropsychologic and/or neurologic deficits. Additional drug rash with eosinophilia was seen in 3 patients, whereas 2 patients showed a highly active demyelinating process. Examination of CSF samples detected pleocytosis, elevated total protein levels, and GFAPα IgG antibodies, which were not found in serum. In our case, we discovered autoimmune GFAP astrocytopathy associated with encephalitis as secondary autoimmunity, which was steroid responsive. Clinical outcome of other cases was marked by partial recovery in 4 patients and persistent foster care in 1 patient. Conclusions Our case of GFAPα IgG-associated encephalitis along with 12 other cases of serious inflammatory brain disorders following daclizumab treatment so far indicates that interfering with NK cells and Tregs by anti-CD25 antibody therapy can result in severe secondary CNS autoimmunity in man.
    Type of Medium: Online Resource
    ISSN: 2332-7812
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 2767740-0
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  • 9
    In: Neurology - Neuroimmunology Neuroinflammation, Ovid Technologies (Wolters Kluwer Health), Vol. 8, No. 3 ( 2021-05), p. e982-
    Abstract: To examine acute (single-bout) and training effects of high-intensity interval training (HIIT) vs standard exercise therapy (moderate continuous training [MCT]) on plasma neurofilament light chain (pNfL) and kynurenine (KYN) pathway of tryptophan degradation metabolites in persons with multiple sclerosis (pwMS). Methods Sixty-nine pwMS (Expanded Disability Status Scale score 3.0–6.0) were randomly assigned to a HIIT or an MCT group. Changes in pNfL and KYN pathway metabolites measured in blood plasma were assessed before, after, and 3 hours after the first training session as well as after the 3-week training intervention. Results Acute exercise reduced pNfL and increased the KYN pathway flux toward the neuroprotective kynurenic acid (KA). Changes in pNfL correlated positively with changes in KA and negatively with the quinolinic acid-to-KA ratio. HIIT consistently led to greater effects than MCT. Following the 3-week training intervention, the KYN pathway was activated in HIIT compared with MCT. Conclusion Future studies and clinical assessments of pNfL should consider acute exercise as confounding factor for measurement reliability. Moreover, exercise-induced KYN pathway rerouting might mediate neuroprotection, potentially underlying the benefits in rehabilitation for pwMS. Classification of Evidence This study provides Class II evidence that acute HIIT diminishes pNfL and increases KA levels, and 3 weeks of HIIT activate the KYN pathway in pwMS. Trial Registration Information Clinical trial registration number: NCT03652519 .
    Type of Medium: Online Resource
    ISSN: 2332-7812
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2767740-0
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  • 10
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 96, No. 15_supplement ( 2021-04-13)
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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