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  • 1
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    Online Resource
    Penumbral Rescue by normobaric O = O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial
    SAGE Publications ; 2023
    In:  International Journal of Stroke
    Details
    In: International Journal of Stroke, SAGE Publications
    Abstract: Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs. Aims: PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion. Methods and design: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial. Study outcomes: Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted. Sample size: Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation. Discussion: By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 h on follow-up imaging reduces variability due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia. Trial registrations: ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31.
    Type of Medium: Online Resource
    ISSN: 1747-4930 , 1747-4949
    URL: Article
    DOI: 10.1177/17474930231185275
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
    detail.hit.zdb_id: 2211666-7
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  • 2
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    Abstracts
    Springer Science and Business Media LLC ; 1994
    In:  Journal of Neuro-Oncology Vol. 21, No. 1 ( 1994-2), p. 1-77
    Details
    In: Journal of Neuro-Oncology, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 1994-2), p. 1-77
    Type of Medium: Online Resource
    ISSN: 0167-594X , 1573-7373
    URL: Article
    DOI: 10.1007/BF01070874
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 1994
    detail.hit.zdb_id: 2007293-4
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  • 3
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    New insights into the genetic etiology of Alzheimer’s disease and related dementias
    Springer Science and Business Media LLC ; 2022
    In:  Nature Genetics Vol. 54, No. 4 ( 2022-04), p. 412-436
    Details
    In: Nature Genetics, Springer Science and Business Media LLC, Vol. 54, No. 4 ( 2022-04), p. 412-436
    Abstract: Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
    Type of Medium: Online Resource
    ISSN: 1061-4036 , 1546-1718
    URL: Article
    DOI: 10.1038/s41588-022-01024-z
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1494946-5
    SSG: 12
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  • 4
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    Predicting poor neurological outcomes following out-of-hospital cardiac arrest using neuron-specific enolase and neurofilament light chain in patients with and without haemolysis
    Oxford University Press (OUP) ; 2023
    In:  European Heart Journal Open Vol. 3, No. 4 ( 2023-07-03)
    Details
    In: European Heart Journal Open, Oxford University Press (OUP), Vol. 3, No. 4 ( 2023-07-03)
    Abstract: Hypoxic-ischaemic brain injury following out-of-hospital cardiac arrest (OHCA) is a common complication and a major cause of death. Neuron-specific enolase (NSE) and neurofilament light chain (NfL) are released after brain injury and elevated concentrations of both are associated with poor neurological outcome. We explored the influence of haemolysis on the prognostic performance of NSE and NfL. Methods and results The study is based on post hoc analyses of a randomized, single-centre, double-blinded, controlled trial (IMICA), where comatose OHCA patients of presumed cardiac cause were included. Free-haemoglobin was measured at admission to quantify haemolysis. NSE and NfL were measured after 48 h to estimate the extent of brain injury. Montreal Cognitive Assessment score (MoCA) was assessed to evaluate neurocognitive impairments. Seventy-three patients were included and divided into two groups by the median free-haemoglobin at admission. No group differences in mortality or poor neurological outcome were observed. The high-admission free-haemoglobin group had a significantly higher concentration of NSE compared to the low-admission free-haemoglobin group (27.4 µmol/L vs. 19.6 µmol/L, P = 0.03), but no differences in NfL. The performance of NSE and NfL in predicting poor neurological outcome were high for both, but NfL was numerically higher [area under the ROC (AUROC) 0.90 vs. 0.96, P = 0.09]. Furthermore, NfL, but not NSE, was inversely correlated with MoCA score, R2 = 0.21, P = 0.006. Conclusion High free-haemoglobin at admission was associated with higher NSE concentration after 48 h, but, the performance of NSE and NfL in predicting poor neurological outcome among OHCA patients were good regardless of early haemolysis. Only elevated NfL concentrations were associated with cognitive impairments.
    Type of Medium: Online Resource
    ISSN: 2752-4191
    URL: Article
    DOI: 10.1093/ehjopen/oead078
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 3112907-9
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  • 5
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    Oxidative Stress and Cardiovascular Risk in Type 1 Diabetes Mellitus: Insights From the DCCT/EDIC Study
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Journal of the American Heart Association Vol. 7, No. 10 ( 2018-05-15)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 7, No. 10 ( 2018-05-15)
    Abstract: Hyperglycemia leading to increased oxidative stress is implicated in the increased risk for the development of macrovascular and microvascular complications in patients with type 1 diabetes mellitus. Methods and Results A random subcohort of 349 participants was selected from the DCCT / EDIC (Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications) cohort. This included 320 controls and 29 cardiovascular disease cases that were augmented with 98 additional known cases to yield a case cohort of 447 participants (320 controls, 127 cases). Biosamples from DCCT baseline, year 1, and closeout of DCCT , and 1 to 2 years post‐ DCCT ( EDIC years 1 and 2) were measured for markers of oxidative stress, including plasma myeloperoxidase, paraoxonase activity, urinary F 2α isoprostanes, and its metabolite, 2,3 dinor‐8 iso prostaglandin F 2α . Following adjustment for glycated hemoblobin and weighting the observations inversely proportional to the sampling selection probabilities, higher paraoxonase activity, reflective of antioxidant activity, and 2,3 dinor‐8 iso prostaglandin F 2α , an oxidative marker, were significantly associated with lower risk of cardiovascular disease (−4.5% risk for 10% higher paraoxonase, P 〈 0.003; −5.3% risk for 10% higher 2,3 dinor‐8 iso prostaglandin F 2α , P =0.0092). In contrast, the oxidative markers myeloperoxidase and F 2α isoprostanes were not significantly associated with cardiovascular disease after adjustment for glycated hemoblobin. There were no significant differences between DCCT intensive and conventional treatment groups in the change in all biomarkers across time segments. Conclusions Heightened antioxidant activity (rather than diminished oxidative stress markers) is associated with lower cardiovascular disease risk in type 1 diabetes mellitus, but these biomarkers did not change over time with intensification of glycemic control. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifiers: NCT 00360815 and NCT 00360893.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.117.008368
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 2653953-6
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  • 6
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    Prognostic value of automated pupillometry: an unselected cohort from a cardiac intensive care unit
    Oxford University Press (OUP) ; 2020
    In:  European Heart Journal. Acute Cardiovascular Care Vol. 9, No. 7 ( 2020-10-01), p. 779-787
    Details
    In: European Heart Journal. Acute Cardiovascular Care, Oxford University Press (OUP), Vol. 9, No. 7 ( 2020-10-01), p. 779-787
    Abstract: Patients admitted to a cardiac intensive care unit are often unconscious with uncertain prognosis. Automated infrared pupillometry for neurological assessment in the intensive care unit may provide early prognostic information. This study aimed to determine the prognostic value of automated pupillometry in different subgroups of patients in a cardiac intensive care unit with 30-day mortality as the primary endpoint and neurological outcome as the secondary endpoint. Methods: A total of 221 comatose patients were divided into three groups: out-of-hospital cardiac arrest, in-hospital cardiac arrest and others (i.e. patients with cardiac diagnoses other than cardiac arrest). Automated pupillometry was serially performed until discharge or death and pupil measurements were analysed using the neurological pupil index algorithm. We applied receiver operating characteristic curves in univariable and multivariable logistic regression models and a calculated Youden index identified neurological pupil index cut-off values at different specificities. Results: In out-of-hospital cardiac arrest patients higher neurological pupil index values were independently associated with lower 30-day mortality. The univariable model for 30-day mortality had an area under the curve of 0.87 and the multivariable model achieved an area under the curve of 0.94. The Youden index identified a neurological pupil index cut-off in out-of-hospital cardiac arrest patients of 2.40 for a specificity of 100%. For patients with in-hospital cardiac arrest and other cardiac diagnoses, we found no association between neurological pupil index values and 30-day mortality, and the univariable models showed poor predictive values. Conclusion: Automated infrared pupillometry has promising predictive value after out-of-hospital cardiac arrest, but poor predictive value in patients with in-hospital cardiac arrest or cardiac diagnoses unrelated to cardiac arrest. Our data suggest a possible neurological pupil index cut-off of 2.40 for poor outcome in out-of-hospital cardiac arrest patients.
    Type of Medium: Online Resource
    ISSN: 2048-8734 , 2048-8726
    URL: Article
    DOI: 10.1177/2048872619842004
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2663340-1
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  • 7
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    Deep sedation as temporary bridge to definitive treatment of ventricular arrhythmia storm
    Oxford University Press (OUP) ; 2020
    In:  European Heart Journal. Acute Cardiovascular Care Vol. 9, No. 6 ( 2020-09-01), p. 657-664
    Details
    In: European Heart Journal. Acute Cardiovascular Care, Oxford University Press (OUP), Vol. 9, No. 6 ( 2020-09-01), p. 657-664
    Abstract: Electrical storm and incessant ventricular tachycardia (VT) are characterized by the clustering of episodes of VT or ventricular fibrillation (VF) and are associated with a poor prognosis. Autonomic nervous system activity influences VT threshold, and deep sedation may be useful for the treatment of VT emergencies. Methods: We reviewed data from conscious patients admitted to our intensive care unit (ICU) due to monomorphic VT, polymorphic VT or VF at our tertiary center between 2010 and 2018. Results: A total of 46 conscious patients with recurrent ventricular arrhythmia, refractory to initial treatment, were referred to the ICU. The majority (n = 31) were stabilized on usual care. The remaining treatment-refractory 15 patients (57 years (range 9–74), 80% males, seven with implantable cardioverter-defibrillators) with VT/VF storm (n = 11) or incessant VT (n = 4) due to ischemic heart disease (n = 10), cardiomyopathy (n = 2), primary arrhythmia (n = 2) and one patient post valve surgery, were deeply sedated and intubated. A complete resolution of VT/VF within minutes to hours was achieved in 12 patients (80%), partial resolution in two (13%) and one (7%) patient died due to ventricular free-wall rupture. One patient with recurrent VT episodes needing repeated deep sedation developed necrotic caecum. No other major complications were seen. Thirteen (87%) patients were alive after a mean follow-up of 3.7 years. Conclusion: Deep sedation was effective and safe for the temporary management of malignant VT/VF refractory to usual treatment. In emergencies, deep sedation may be widely accessible at both secondary and tertiary centers and a clinically useful bridge to definitive treatment of VT.
    Type of Medium: Online Resource
    ISSN: 2048-8734 , 2048-8726
    URL: Article
    DOI: 10.1177/2048872620903453
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2663340-1
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  • 8
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    Arterial blood pressure during targeted temperature management after out-of-hospital cardiac arrest and association with brain injury and long-term cognitive function
    Oxford University Press (OUP) ; 2020
    In:  European Heart Journal. Acute Cardiovascular Care Vol. 9, No. 4_suppl ( 2020-11-01), p. S122-S130
    Details
    In: European Heart Journal. Acute Cardiovascular Care, Oxford University Press (OUP), Vol. 9, No. 4_suppl ( 2020-11-01), p. S122-S130
    Abstract: During targeted temperature management after out-of-hospital cardiac arrest infusion of vasoactive drugs is often needed to ensure cerebral perfusion pressure. This study investigated mean arterial pressure after out-of-hospital cardiac arrest and the association with brain injury and long-term cognitive function. Methods: Post-hoc analysis of patients surviving at least 48 hours in the biobank substudy of the targeted temperature management trial with available blood pressure data. Patients were stratified in three groups according to mean arterial pressure during targeted temperature management (4–28 hours after admission; & lt;70 mmHg, 70–80 mmHg, & gt;80 mmHg). A biomarker of brain injury, neuron-specific enolase, was measured and impaired cognitive function was defined as a mini-mental state examination score below 27 in 6-month survivors. Results: Of the 657 patients included in the present analysis, 154 (23%) had mean arterial pressure less than 70 mmHg, 288 (44%) had mean arterial pressure between 70 and 80 mmHg and 215 (33%) had mean arterial pressure greater than 80 mmHg. There were no statistically significant differences in survival (P=0.35) or neuron-specific enolase levels (P=0.12) between the groups. The level of target temperature did not statistically significantly interact with mean arterial pressure regarding neuron-specific enolase (Pinteraction_MAP*TTM=0.58). In the subgroup of survivors with impaired cognitive function (n=132) (35%) mean arterial pressure during targeted temperature management was significantly higher (Pgroup=0.03). Conclusions: In a large cohort of comatose out-of-hospital cardiac arrest patients, low mean arterial pressure during targeted temperature management was not associated with higher neuron-specific enolase regardless of the level of target temperature (33°C or 36°C for 24 hours). In survivors with impaired cognitive function, mean arterial pressure during targeted temperature management was significantly higher.
    Type of Medium: Online Resource
    ISSN: 2048-8734 , 2048-8726
    URL: Article
    DOI: 10.1177/2048872619860804
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2663340-1
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  • 9
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    Epidemiology, monitoring, and treatment strategy in cardiogenic shock. A multinational cross-sectional survey of ESC-acute cardiovascular care association research section
    Oxford University Press (OUP) ; 2022
    In:  European Heart Journal. Acute Cardiovascular Care Vol. 11, No. 9 ( 2022-09-29), p. 706-711
    Details
    In: European Heart Journal. Acute Cardiovascular Care, Oxford University Press (OUP), Vol. 11, No. 9 ( 2022-09-29), p. 706-711
    Abstract: Cardiogenic shock (CS) is a life-threatening condition burdened by mortality in up to 50% of cases. Few recommendations exist with intermediate–low level of evidence on CS management and no data on adherence across centres exist. We performed a survey to frame CS management at multinational level. Methods and results An international cross-sectional survey was created and approved by European Society of Cardiology-Acute Cardiovascular Care Association board. A total of 337 responses from 60 countries were obtained. Data were assessed by the hospital level of care of the participants. The most common cause of CS was AMI (AMI-CS—79.9%) with significant difference according to hospital levels (P = 0.001), followed by acutely decompensated heart failure (HF) (13.4%), myocarditis (3.5%), and de novo HF (1.75%). In 37.8%, percutaneous coronary intervention (PCI) is performed to all CS-patients as a standard approach, whereas 42.1% used PCI if electrocardiogram suggestive of ischaemia and 20.1% only if Universal definition of myocardial infarction criteria are fulfilled. Management (catecholamine titration and mechanical circulatory support escalation) is driven by mean arterial pressure (87.1%), echocardiography (84.4%), and lactate levels (83.4%). Combination of vasopressor and inotrope is chosen with the same frequency (37.7%) than inotrope alone as first-line pharmacological therapy (differences amongst hospital levels; P  & gt; 0.5). Noradrenaline is first-line vasopressor (89.9%) followed by dopamine (8.5%), whereas dobutamine is confirmed as the first-line inotrope (65.9%). Conclusion Cardiogenic shock management is heterogenous and often not adherent to current recommendations. Quality improvement on an international level with evidence-based quality indicators should be developed to standardize diagnostic and therapeutic pathways.
    Type of Medium: Online Resource
    ISSN: 2048-8726 , 2048-8734
    URL: Article
    DOI: 10.1093/ehjacc/zuac087
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2663340-1
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  • 10
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    Meeting abstracts from the 7th Danish Emergency Medicine Conference : Copenhagen, Denmark. 24 - 25 November 2016
    Springer Science and Business Media LLC ; 2017
    In:  Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine Vol. 25, No. S2 ( 2017-3)
    Details
    In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, Springer Science and Business Media LLC, Vol. 25, No. S2 ( 2017-3)
    Type of Medium: Online Resource
    ISSN: 1757-7241
    URL: Article
    DOI: 10.1186/s13049-017-0364-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2455990-8
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