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- Marto, João Pedro, et al.
(författare)
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Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:7
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT).Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60).Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis.The study was registered under ClinicalTrials.gov identifier NCT04895462.
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| 4. |
- Forteza, Maria J., et al.
(författare)
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Pyruvate dehydrogenase kinase regulates vascular inflammation in atherosclerosis and increases cardiovascular risk
- 2023
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Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 119:7, s. 1524-1536
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have revealed a close connection between cellular metabolism and the chronic inflammatory process of atherosclerosis. While the link between systemic metabolism and atherosclerosis is well established, the implications of altered metabolism in the artery wall are less understood. Pyruvate dehydrogenase kinase (PDK)-dependent inhibition of pyruvate dehydrogenase (PDH) has been identified as a major metabolic step regulating inflammation. Whether the PDK/PDH axis plays a role in vascular inflammation and atherosclerotic cardiovascular disease remains unclear. Methods and results Gene profiling of human atherosclerotic plaques revealed a strong correlation between PDK1 and PDK4 transcript levels and the expression of pro-inflammatory and destabilizing genes. Remarkably, the PDK1 and PDK4 expression correlated with a more vulnerable plaque phenotype, and PDK1 expression was found to predict future major adverse cardiovascular events. Using the small-molecule PDK inhibitor dichloroacetate (DCA) that restores arterial PDH activity, we demonstrated that the PDK/PDH axis is a major immunometabolic pathway, regulating immune cell polarization, plaque development, and fibrous cap formation in Apoe−/− mice. Surprisingly, we discovered that DCA regulates succinate release and mitigates its GPR91-dependent signals promoting NLRP3 inflammasome activation and IL-1β secretion by macrophages in the plaque. Conclusions We have demonstrated for the first time that the PDK/PDH axis is associated with vascular inflammation in humans and particularly that the PDK1 isozyme is associated with more severe disease and could predict secondary cardiovascular events. Moreover, we demonstrate that targeting the PDK/PDH axis with DCA skews the immune system, inhibits vascular inflammation and atherogenesis, and promotes plaque stability features in Apoe−/− mice. These results point toward a promising treatment to combat atherosclerosis.
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| 5. |
- Grinnemo, Karl-Henrik, et al.
(författare)
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Immunomodulatory effects of interferon-gamma on human fetal cardiac mesenchymal stromal cells
- 2019
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Ingår i: Stem Cell Research & Therapy. - : BMC. - 1757-6512. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mesenchymal stromal cells (MSCs), due to their regenerative and immunomodulatory properties, are therapeutically used for diseases, including heart failure. As early gestational-phase embryonic tissues exhibit extraordinary regenerative potential, fetal MSCs exposed to inflammation offer a unique opportunity to evaluate molecular mechanisms underlying preferential healing, and investigate their inherent abilities to communicate with the immune system during development. The principal aim of this study was to evaluate the effects of interferon-gamma (IFN gamma) on the immunomodulatory effects of first-trimester human fetal cardiac (hfc)-MSCs.Methods: hfcMSCs (gestational week 8) were exposed to IFN gamma, with subsequent analysis of the whole transcriptome, based on RNA sequencing. Exploration of surface-expressed immunoregulatory mediators and modulation of T cell responses were performed by flow cytometry. Presence and activity of soluble mediators were assessed by ELISA or high-performance liquid chromatography.Results: Stimulation of hfcMSCs with IFN gamma revealed significant transcriptional changes, particularly in respect to the expression of genes belonging to antigen presentation pathways, cell cycle control, and interferon signaling. Expression of immunomodulatory genes and associated functional changes, including indoleamine 2,3-dioxygenase activity, and regulation of T cell activation and proliferation via programmed cell death protein (PD)-1 and its ligands PD-L1 and PD-L2, were significantly upregulated. These immunoregulatory molecules diminished rapidly upon withdrawal of inflammatory stimulus, indicating a high degree of plasticity by hfcMSCs.Conclusions: To our knowledge, this is the first study performing a systematic evaluation of inflammatory responses and immunoregulatory properties of first-trimester cardiac tissue. In summary, our study demonstrates the dynamic responsiveness of hfcMSCs to inflammatory stimuli. Further understanding as to the immunoregulatory properties of hfcMSCs may be of benefit in the development of novel stromal cell therapeutics for cardiovascular disease.
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| 6. |
- Jünger, Christian, et al.
(författare)
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Magnetic-Field-Independent Subgap States in Hybrid Rashba Nanowires
- 2020
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Ingår i: Physical Review Letters. - 0031-9007. ; 125:1
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Tidskriftsartikel (refereegranskat)abstract
- Subgap states in semiconducting-superconducting nanowire hybrid devices are controversially discussed as potential topologically nontrivial quantum states. One source of ambiguity is the lack of an energetically and spatially well defined tunnel spectrometer. Here, we use quantum dots directly integrated into the nanowire during the growth process to perform tunnel spectroscopy of discrete subgap states in a long nanowire segment. In addition to subgap states with a standard magnetic field dependence, we find topologically trivial subgap states that are independent of the external magnetic field, i.e., that are pinned to a constant energy as a function of field. We explain this effect qualitatively and quantitatively by taking into account the strong spin-orbit interaction in the nanowire, which can lead to a decoupling of Andreev bound states from the field due to a spatial spin texture of the confined eigenstates. This result constitutes an important step forward in the research on superconducting subgap states in nanowires, such as Majorana bound states.
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| 7. |
- Kumawat, Ashok Kumar, 1982-, et al.
(författare)
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Inhibition of IL17A Using an Affibody Molecule Attenuates Inflammation in ApoE-Deficient Mice
- 2022
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Ingår i: Frontiers in Cardiovascular Medicine. - : Frontiers Media S.A.. - 2297-055X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The balance between pro- and anti-inflammatory cytokines released by immune and non-immune cells plays a decisive role in the progression of atherosclerosis. Interleukin (IL)-17A has been shown to accelerate atherosclerosis. In this study, we investigated the effect on pro-inflammatory mediators and atherosclerosis development of an Affibody molecule that targets IL17A. Affibody molecule neutralizing IL17A, or sham were administered in vitro to human aortic smooth muscle cells (HAoSMCs) and murine NIH/3T3 fibroblasts and in vivo to atherosclerosis-prone, hyperlipidaemic ApoE(-/-) mice. Levels of mediators of inflammation and development of atherosclerosis were compared between treatments. Exposure of human smooth muscle cells and murine NIH/3T3 fibroblasts in vitro to alpha IL-17A Affibody molecule markedly reduced IL6 and CXCL1 release in supernatants compared with sham exposure. Treatment of ApoE(-/-) mice with alpha IL-17A Affibody molecule significantly reduced plasma protein levels of CXCL1, CCL2, CCL3, HGF, PDGFB, MAP2K6, QDPR, and splenocyte mRNA levels of Ccxl1, Il6, and Ccl20 compared with sham exposure. There was no significant difference in atherosclerosis burden between the groups. In conclusion, administration of alpha IL17A Affibody molecule reduced levels of pro-inflammatory mediators and attenuated inflammation in ApoE(-/-) mice.
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| 8. |
- Kuster, Roman P, et al.
(författare)
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Active sitting with backrest support : is it feasible?
- 2018
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Ingår i: Ergonomics. - Stockholm : Karolinska Institutet, Dept of Neurobiology, Care Sciences and Society. - 0014-0139 .- 1366-5847.
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Tidskriftsartikel (refereegranskat)abstract
- Ergonomics science recommends office chairs that promote active sitting to reduce sitting related complaints. Since current office chairs do not fulfil this recommendation, a new chair was developed by inverting an existing dynamic chair principle. This study compares active sitting on the inverted chair during a simulated computer based office task to two existing dynamic office chairs (n=8). Upper body stability was analysed using Friedman ANOVA (p=.01). Additionally, participants completed a questionnaire to rate their comfort and activity after half a working day. The inverted chair allowed the participants to perform a substantial range of lateral spine flexion (11.5°) with the most stable upper body posture (≤11mm, ≤2°, p≤0.01). The results of this study suggest that the inverted chair supports active sitting with backrest support during computer based office work. However, according to comfort and activity ratings, results should be verified in a future field study with 24 participants.
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| 9. |
- Kuster, Roman P, et al.
(författare)
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Detecting Prolonged Sitting Bouts with the ActiGraph GT3X.
- 2020
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - Stockholm : Wiley-Blackwell. - 0905-7188 .- 1600-0838. ; 30:3, s. 572-582
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Tidskriftsartikel (refereegranskat)abstract
- The ActiGraph has a high ability to measure physical activity, however, it lacks an accurate posture classification to measure sedentary behaviour. The aim of the present study was to develop an ActiGraph (waist-worn, 30Hz) posture classification to detect prolonged sitting bouts, and to compare the classification to proprietary ActiGraph data. The activPAL, a highly valid posture classification device, served as reference criterion.1 Both sensors were worn by 38 office workers over a median duration of 9 days. An automated feature selection extracted the relevant signal information for a minute based posture classification. The machine-learning algorithm with optimal feature number to predict the time in prolonged sitting bouts (≥5 and ≥10 minutes) was searched and compared to the activPAL using Bland-Altman statistics. The comparison included optimised and frequently used cut-points (100 and 150 counts-per-minute (cpm), with and without low-frequency-extension (LFE) filtering). The new algorithm predicted the time in prolonged sitting bouts most accurate (bias ≤7 minutes/day). Of all proprietary ActiGraph methods, only 150 cpm without LFE predicted the time in prolonged sitting bouts non-significantly different from the activPAL (bias ≤18 minutes/day). However, the frequently used 100 cpm with LFE accurately predicted total sitting time (bias ≤7 minutes/day). To study the health effects of ActiGraph measured prolonged sitting, we recommend using the new algorithm. In case a cut-point is used, we recommend 150 cpm without LFE to measure prolonged sitting, and 100 cpm with LFE to measure total sitting time. However, both cpm cut-points are not recommended for a detailed bout analysis.
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| 10. |
- Kuster, Roman P, et al.
(författare)
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How Accurate and Precise Can We Measure the Posture and the Energy Expenditure Component of Sedentary Behaviour with One Sensor?
- 2021
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 18:11
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Tidskriftsartikel (refereegranskat)abstract
- Sedentary behaviour is an emergent public health topic, but there is still no method to simultaneously measure both components of sedentary behaviour-posture and energy expenditure-with one sensor. This study investigated the accuracy and precision of measuring sedentary time when combining the proprietary processing of a posture sensor (activPAL) with a new energy expenditure algorithm and the proprietary processing of a movement sensor (ActiGraph) with a published posture algorithm. One hundred office workers wore both sensors for an average of 7 days. The activPAL algorithm development used 38 and the subsequent independent method comparison 62 participants. The single sensor sedentary estimates were compared with Bland-Atman statistics to the Posture and Physical Activity Index, a combined measurement with both sensors. All single-sensor methods overestimated sedentary time. However, adding the algorithms reduced the overestimation from 129 to 21 (activPAL) and from 84 to 7 min a day (ActiGraph), with far narrower 95% limits of agreements. Thus, combining the proprietary data with the algorithms is an easy way to increase the accuracy and precision of the single sensor sedentary estimates and leads to sedentary estimates that are more precise at the individual level than those of the proprietary processing are at the group level.
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