| 1. |
- Kar, Rohan, et al.
(författare)
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The FBXW7-NOTCH interactome : A ubiquitin proteasomal system-induced crosstalk modulating oncogenic transformation in human tissues
- 2021
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Ingår i: Cancer Reports. - : John Wiley & Sons. - 2573-8348. ; 4:4
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Forskningsöversikt (refereegranskat)abstract
- Background Ubiquitin ligases or E3 ligases are well programmed to regulate molecular interactions that operate at a post-translational level. Skp, Cullin, F-box containing complex (or SCF complex) is a multidomain E3 ligase known to mediate the degradation of a wide range of proteins through the proteasomal pathway. The three-dimensional domain architecture of SCF family proteins suggests that it operates through a novel and adaptable "super-enzymatic" process that might respond to targeted therapeutic modalities in cancer. Recent findings Several F-box containing proteins have been characterized either as tumor suppressors (FBXW8, FBXL3, FBXW8, FBXL3, FBXO1, FBXO4, and FBXO18) or as oncogenes (FBXO5, FBXO9, and SKP2). Besides, F-box members like beta TrcP1 and beta TrcP2, the ones with context-dependent functionality, have also been studied and reported. FBXW7 is a well-studied F-box protein and is a tumor suppressor. FBXW7 regulates the activity of a range of substrates, such as c-Myc, cyclin E, mTOR, c-Jun, NOTCH, myeloid cell leukemia sequence-1 (MCL1), AURKA, NOTCH through the well-known ubiquitin-proteasome system (UPS)-mediated degradation pathway. NOTCH signaling is a primitive pathway that plays a crucial role in maintaining normal tissue homeostasis. FBXW7 regulates NOTCH protein activity by controlling its half-life, thereby maintaining optimum protein levels in tissue. However, aberrations in the FBXW7 or NOTCH expression levels can lead to poor prognosis and detrimental outcomes in patients. Therefore, the FBXW7-NOTCH axis has been a subject of intense study and research over the years, especially around the interactome's role in driving cancer development and progression. Several studies have reported the effect of FBXW7 and NOTCH mutations on normal tissue behavior. The current review attempts to critically analyze these mutations prognostic value in a wide range of tumors. Furthermore, the review summarizes the recent findings pertaining to the FBXW7 and NOTCH interactome and its involvement in phosphorylation-related events, cell cycle, proliferation, apoptosis, and metastasis. Conclusion The review concludes by positioning FBXW7 as an effective diagnostic marker in tumors and by listing out recent advancements made in cancer therapeutics in identifying protocols targeting the FBXW7-NOTCH aberrations in tumors.
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| 2. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 3. |
- Dixit, Sudhir, et al.
(författare)
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Connecting the Unconnected
- 2022
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Ingår i: 2022 IEEE FUTURE NETWORKS WORLD FORUM, FNWF. - : IEEE. - 9781665462501
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Konferensbidrag (refereegranskat)abstract
- Connecting the Unconnected or under-connected (CTU) is the holy grail of transforming the lives of over 3 billion people around the globe with wireless Internet who are yet to experience its value in multiple ways. If this could be accomplished, its impact on the society would be enormous. This white paper from the IEEE Future Networks CTU Working Group endeavors to highlight the need to consider the CTU requirements in 5G and B5G networks in the standardization process, in the development of the use cases, and affordable solutions. In its Vision 2030 SDG (Sustainability Development Goals) the United Nations has proclaimed access to Internet as basic human right and has said that these goals cannot be achieved without affordable access to Internet by everyone on this planet. While there are numerous projects and initiatives ongoing around the world, these are fragmented and lack the critical mass and coordination to be able to impact the future standards, product development, and cost of deployment otherwise achievable by volume. Although difficult to pin down, to define a threshold for basic connectivity for all is important. But it would need to be flexible to adapt to changing times. It is the goal of the CTU group to create an open platform where the experts can bring their ideas, solutions, and potentially collaborate to create large global projects and influence the network service providers, manufacturers and their governments. This white paper defines the CTU working group's charter, scope, and provides a brief overview of the relevant stakeholders and linkages between them. Then the paper goes into the current status of the CTU landscape and where we want to reach to accomplish the vision of connecting everybody, especially those living in rural and remote areas. We present the various standards and industry fora and how they are interlinked. While technologies are available today, they need to be customized and optimized at the systems level to bring down the cost of the network in order to be affordable. In addition, the content needs to be relevant and in local languages to be useful, not to mention the need to offer innovative human computer interaction (HCI) solutions (that are not text based) so that people who are not literate or are digitally disadvantaged can easily use the devices and consume services. Another important area is that of flexible spectrum allocation regime at the lower range of the spectrum to increase reach and coverage. Use of renewable energy sources will enable deployment in remote areas where there is lack of power grid, or it is intermittent. Thus, this white paper identifies a number of technology gaps to be filled in by 5G and B5G networks, such that access is affordable and content and services are actually consumed by the targeted set of users. Technology aside, the need to develop innovative business models is a must to be commercially sustainable in the long-term. A number of such models, especially designed for the rural population, are proposed, such as Village Level Entrepreneur (VLE) Freemium (Free + Premium), revenue sharing among the chain of service providers, subsidized billing by USOF (Universal Service Obligation Funds). Finally, the white paper presents a 10-year roadmap starting from the current state to 3 years, 5 years and 10 years.
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| 4. |
- Hammarsten, Ola, et al.
(författare)
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The ratio of cardiac troponin T to troponin I may indicate non-necrotic troponin release among COVID-19 patients
- 2022
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Ingår i: Clinica Chimica Acta. - : Elsevier. - 0009-8981 .- 1873-3492. ; 527, s. 33-37
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although cardiac troponin T (cTnT) and troponin I(cTnI) are expressed to similar amount in cardiac tissue, cTnI often reach ten-times higher peak levels compared to cTnT in patients with myocardial necrosis such as in acute myocardial infarction (MI). In contrast, similar levels of cTnT and cTnI are observed in other situations such as stable atrial fibrillation and after strenuous exercise.Objective: Examine cTnT and cTnI levels in relation to COVID-19 disease and MI. Methods: Clinical and laboratory data from the local hospital from an observational cohort study of 27 patients admitted with COVID-19 and 15 patients with myocardial infarction (MI) that were analyzed with paired cTnT and cTnI measurement during hospital care.Results: Levels of cTnI were lower than cTnT in COVID-19 patients (TnI/TnT ratio 0.3, IQR: 0.1-0.6). In contrast, levels of cTnI were 11 times higher compared to cTnT in 15 patients with MI (TnI/TnT ratio 11, IQR: 7-14). The peak cTnI/cTnT ratio among the patients with MI following successful percutaneous intervention were 14 (TnI/ TnT ratio 14, IQR: 12-23). The 5 COVID-19 patient samples collected under possible necrotic events had a cTnI/ cTnT ratio of 5,5 (IQR: 1,9-8,3).Conclusions: In patients with COVID-19, cTnT is often elevated to higher levels than cTnI in sharp contrast to patients with MI, indicating that the release of cardiac troponin has a different cause in COVID-19 patients.
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| 5. |
- Jha, Sandeep, et al.
(författare)
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Clinical management in the takotsubo syndrome.
- 2019
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Ingår i: Expert review of cardiovascular therapy. - : Informa UK Limited. - 1744-8344 .- 1477-9072. ; 17:2, s. 83-93
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Forskningsöversikt (refereegranskat)abstract
- Takotsubo syndrome (TS) is an increasingly recognized acute heart failure syndrome which is self-limiting in most cases but can result in life-threatening complications. TS is difficult to distinguish from acute myocardial infarction (AMI) early in the disease course and currently lacks evidence-based treatment recommendations. Areas covered: Based on the available literature this systematic review discusses the clinical management of patients with TS during (i) the diagnostic workup; (ii) acutely after establishing the TS diagnosis; and (iii) after recovery of cardiac function. Expert commentary Since TS is self-limiting in most cases it is recommended to refrain from unnecessary treatment (the do no harm principle) when managing patients with TS. The management of patients with TS should focus on careful monitoring of ECG and hemodynamics, and on preventing and treating complications. Because catecholamine-mediated inotropic overstimulation is implicated in the pathogenesis of TS, and because inotropic drugs have been associated with worse outcomes for patients with TS, we recommend the treating physician to avoid these drugs. Instead, mechanical assist devices should be considered early for patients with TS who develop cardiogenic shock with signs of end-organ hypo-perfusion.
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| 6. |
- Jha, Sandeep, et al.
(författare)
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Electrocardiographic predictors of adverse in-hospital outcomes in the Takotsubo syndrome.
- 2020
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Ingår i: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 299, s. 43-48
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Tidskriftsartikel (refereegranskat)abstract
- Takotsubo syndrome (TS) is a life-threatening acute heart failure syndrome. However, little is known about risk factors for worse outcomes in TS and no high-risk ECG criteria have been defined. We sought to identify ECG predictors of life-threatening in-hospital complications in TS.Using the nationwide Swedish Angiography and Angioplasty Registry (SCAAR) we obtained data on all consecutive patients undergoing coronary angiography at Sahlgrenska University Hospital between June 2008 and February 2019. For all patients with TS we conducted in-depth chart reviews to confirm the TS diagnosis. For those with confirmed TS we then evaluated all ECGs obtained during the index hospitalization. The primary endpoint was the occurrence of in-hospital major adverse cardiac event (MACE), defined as the composite of death, ventricular tachycardia or fibrillation (VT/VF), or atrioventricular block ≥2 or asystole ≫10s. We identified 215 patients with TS (mean age 69±13years; 93% women). MACE occurred in 34 patients (16%), of whom 20 had VT/VF (9,3%). Patients with MACE were less likely than those without MACE to have sinus rhythm (85% versus 96%, p=0.025) or T-wave inversion (29% versus 51%, p=0.025). After propensity score adjustment T-wave inversion was independently associated with lower MACE risk (adjusted odds ratio [AdjOR] 0.28, 95% confidence interval [CI] 0.10-0.76, p=0.012) and VT/VF (AdjOR 0.24, 95% CI 0.06-0.94, p=0.041).T-wave inversion is common in TS and is associated with lower risk of MACE, driven by a lower risk of VT/VF.
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| 7. |
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| 8. |
- Poller, Angela, 1988, et al.
(författare)
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Inter- and intra-observer variability in the echocardiographic evaluation of wall motion abnormality in patients with ST-elevation myocardial infarction or takotsubo syndrome - A novel approach
- 2023
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Ingår i: Echocardiography-a Journal of Cardiovascular Ultrasound and Allied Techniques. - 0742-2822. ; 40:7, s. 711-719
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Tidskriftsartikel (refereegranskat)abstract
- Introduction and ObjectivesUsing existing transthoracic echocardiographic indices to quantify left ventricular wall motion abnormalities (WMAs) can be difficult due to the variations in the location of the abnormalities within the left ventricle, the quality of examinations, and the inter-/intra-observer variability of available indices. This study aimed to evaluate a new approach for measuring the extent of WMA by calculating the percentage of abnormal wall motion and comparing it to the wall motion score index (WMSI). The study also sought to assess inter- and intra-observer variability. MethodsThe study included 140 echocardiograms from 54 patients presenting with ST-elevation myocardial infarction or Takotsubo syndrome. All patients underwent an echocardiographic examination according to a standard protocol and the images were used to measure the extent of akinesia (proportion akinesia, PrA), akinesia and hypokinesia (proportion akinesia/hypokinesia, PrAH), and WMSI. The inter-observer variability between the two operators was analyzed. The intra-observer analysis was performed by one observer using the same images at least 1 month after the first measurement. The agreement was analyzed using the Pearson correlation coefficient and Bland-Altman plots. ResultsInter- and intra-observer variability for PrA and PrAH were low and comparable to those for WMSI. ConclusionPrA and PrAH are reliable and reproducible echocardiographic methods for the evaluation of left ventricular wall motion.
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| 9. |
- Redfors, Björn, et al.
(författare)
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Short- and Long-Term Clinical Outcomes for Patients With Takotsubo Syndrome and Patients With Myocardial Infarction : A Report From the Swedish Coronary Angiography and Angioplasty Registry
- 2021
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Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 10:17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Takotsubo syndrome (TS) is a potentially life-threatening acute cardiac syndrome with a clinical presentation similar to myocardial infarction and for which the natural history, management, and outcome remain incompletely understood. Our aim was to assess the relative short-term mortality risk of TS, ST-segment-elevation myocardial infarction (STEMI), and non-STEMI (NSTEMI) and to identify predictors of in-hospital complications and poor prognosis in patients with TS.Methods and Results: This is an observational cohort study based on the data from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry). We included all patients (n=117 720) who underwent coronary angiography in Sweden attributed to TS (N=2898 [2.5%]), STEMI (N=48 493 [41.2%]), or NSTEMI (N=66 329 [56.3%]) between January 2009 and February 2018. We compared patients with TS to those with NSTEMI or STEMI. The primary end point was all-cause mortality at 30 days. Secondary outcomes were acute heart failure (Killip Class ≥2) and cardiogenic shock (Killip Class 4) at the time of angiography. Patients with TS were more often women compared with patients with STEMI or NSTEMI. TS was associated with unadjusted and adjusted 30-day mortality risks lower than STEMI (adjusted hazard ratio [adjHR], 0.60; 95% CI, 0.48-0.76; P<0.001), but higher than NSTEMI (adjHR, 2.70; 95% CI, 2.14-3.41; P<0.001). Compared with STEMI, TS was associated with a similar risk of acute heart failure (adjHR, 1.26; 95% CI, 0.91-1.76; P=0.16) but a lower risk of cardiogenic shock (adjHR, 0.55; 95% CI, 0.34-0.89; P=0.02). The relative 30-day mortality risk for TS versus STEMI and NSTEMI was higher for smokers than nonsmokers (adjusted P interaction STEMI=0.01 and P interaction NSTEMI=0.01). Conclusions: The 30-day mortality rate in TS was higher than in NSTEMI but lower than STEMI despite a similar risk of acute heart failure in TS and STEMI. Among patients with TS, smoking was an independent predictor of mortality.
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| 10. |
- Shekka Espinosa, Aaron, et al.
(författare)
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Differences between cardiac troponin I vs. T according to the duration of myocardial ischaemia
- 2023
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Ingår i: European Heart Journal-Acute Cardiovascular Care. - : Oxford University Press (OUP). - 2048-8726 .- 2048-8734. ; 12:6, s. 355-363
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Tidskriftsartikel (refereegranskat)abstract
- Aims Cardiac troponin T (cTnT) and troponin I (cTnI) are expressed as an obligate 1:1 complex in the myocardium. However, blood levels of cTnI often rise much higher than that of cTnT in myocardial infarction (MI), whereas cTnT is often higher in patients with stable conditions such as atrial fibrillation. Here we examine high-sensitive (hs) cTnI and hs-cTnT after different durations of experimental cardiac ischaemia. Methods and results hs-cTnI, hs-cTnT, and the hs-cTnT/hs-cTnI ratio were measured in plasma samples from rats before and at 30 and 120 min after 5, 10, 15, and 30 min of myocardial ischaemia. The animals were killed after 120 min of reperfusion, and the infarct volume and volume at risk were measured. hs-cTnI, hs-cTnT, and the hs-cTnT/hs-cTnI ratio were also measured in plasma samples collected from patients with ST-elevation myocardial infarction (STEMI). hs-cTnT and hs-cTnI increased over 10-fold in all rats subjected to ischaemia. The increase of hs-cTnI and hs-cTnT after 30 min was similar, resulting in a hs-cTnI/hs-cTnT ratio around 1. The hs-cTnI/hs-cTnT ratio was also around 1 in blood samples collected at 120 min in rats subjected to 5 or 10 min of ischaemia where no localized necrosis was observed. In contrast, the hs-cTnI/hs-cTnT ratio at 2 h was 3.6-5.5 after longer ischaemia that induced cardiac necrosis. The large hs-cTnI/hs-cTnT ratio was confirmed in patients with anterior STEMI. Conclusion Both hs-cTnI and hs-cTnT increased similarly after brief periods of ischaemia that did not cause overt necrosis, whereas the hs-cTnI/hs-cTnT ratio tended to increase following longer ischaemia that induced substantial necrosis. A low hs-cTnI/hs-cTnT ratio around 1 may signify non-necrotic cTn release.
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| 11. |
- Zeijlon, Rickard, et al.
(författare)
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ECG differences and ECG predictors in patients presenting with ST segment elevation due to myocardial infarction versus takotsubo syndrome.
- 2022
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Ingår i: International journal of cardiology. Heart & vasculature. - : Elsevier BV. - 2352-9067. ; 40:June 2022
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies comparing electrocardiogram (ECG) in Takotsubo syndrome (TS) versus ST elevation myocardial infarction (STEMI) included TS patients without ST elevation, did not consider the culprit lesion in STEMI or had groups that were unbalanced regarding sex and age. Accounting for these factors, we sought to conduct a more reliable comparison of ECG in TS with ST-elevation (STE-TS) versus STEMI. The secondary aim was to investigate if ST segment changes, T wave inversion or prolonged QT interval predicted ventricular arrhythmia or death in STE-TS and STEMI.All STE-TS patients who presented at Sahlgrenska University Hospital between 2008 and 2019 were matched by sex and age to STEMI patients. STEMI patients were subcategorized according to whether or not the culprit lesion was located in the left anterior descending artery (LAD). Baseline characteristics, in-hospital outcomes and admission ECGs were analyzed.104 STE-TS patients were sex- and age-matched with 274 STEMI patients (113 LAD-STEMI, 161 non-LAD STEMI). Admission ECG in STE-TS was more similar to LAD STEMI than non-LAD STEMI. Reciprocal ST depression was less common in STE-TS (7/104, 6.7%) compared with STEMI (112/274, 41%; p=<0.001). The sum of all ST elevations and the sum of all ST-deviations predicted life-threatening ventricular arrhythmia (LTVA) or death in LAD STEMI but not in STE-TS.In conclusion, admission ECG in STE-TS was similar to LAD STEMI but reciprocal ST depression was less common in STE-TS compared with STEMI overall. ST segment changes predicted LTVA or death in STEMI but not in STE-TS.
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| 12. |
- Zeijlon, Rickard, et al.
(författare)
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Risk of in-hospital life-threatening ventricular arrhythmia or death after ST-elevation myocardial infarction vs. the Takotsubo syndrome.
- 2021
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Ingår i: ESC heart failure. - : Wiley. - 2055-5822. ; 8:2, s. 1314-1323
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Tidskriftsartikel (refereegranskat)abstract
- The risk of life-threatening ventricular arrhythmias (LTVA) has been reported to be lower in Takotsubo syndrome (TS) compared with ST-elevation myocardial infarction (STEMI). However, the extent to which these differences relate to the fact that most patients with TS are women (who have a lower risk of LTVA) and a relatively larger proportion of patients with STEMI are men is incompletely understood. We aimed to investigate the risk of LTVA or death in sex-matched and age-matched patients with TS, anterior STEMI, and non-anterior STEMI.We systematically reviewed the charts of all patients with TS who were treated at Sahlgrenska University Hospital (Gothenburg, Sweden) between 2008 and 2019. A total of 155 patients with confirmed TS (according to the European Society of Cardiology diagnostic criteria for TS) were sex-matched and age-matched 1:1:1 to patients with anterior and non-anterior STEMI. Baseline characteristics and in-hospital outcomes were recorded directly from the patient charts for all patients, and all admission electrocardiographs were analysed. The primary outcome was the composite of death or LTVA [defined as sustained ventricular tachycardia (>30s) or ventricular fibrillation] within 72h. The risk of LTVA or death within 72h after admission was considerably lower in TS (2.6%) vs. anterior STEMI (14%; P=0.002) and non-anterior STEMI (9.0%; P=0.02), despite similar or greater risks of acute heart failure, and similar risks of cardiogenic shock. Compared with STEMI, TS was associated with a lower risk of sustained and non-sustained ventricular tachycardia and ventricular fibrillation.In a predominantly female age-matched and sex-matched cohort of patients with TS, anterior STEMI, and non-anterior STEMI, the adjusted risk of in-hospital LTVA or death was considerably lower in TS compared with STEMI, despite similar or greater risk of acute heart failure and similar risk of cardiogenic shock.
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| 13. |
- Zeijlon, Rickard, et al.
(författare)
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Temporal electrocardiographic changes in anterior ST elevation myocardial infarction versus the Takotsubo syndrome.
- 2023
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Ingår i: International journal of cardiology. Heart & vasculature. - : Elsevier BV. - 2352-9067. ; 45
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Tidskriftsartikel (refereegranskat)abstract
- Electrocardiography (ECG) on admission is similar in ST elevation myocardial infarction (STEMI) and Takotsubo syndrome (TTS). ECG on admission has been extensively investigated and compared between STEMI and TTS, however, only a few studies have compared temporal ECG. Our aim was to compare ECG in anterior STEMI versus female TTS from admission to day 30.Adult patients with anterior STEMI or TTS treated at Sahlgrenska University Hospital (Gothenburg, Sweden) from December 2019 to June 2022 were prospectively enrolled. Baseline characteristics, clinical variables and ECGs from admission to day 30 were analyzed. Using a mixed effects model, we compared temporal ECG between female patients with anterior STEMI or TTS, as well as between female and male patients with anterior STEMI.A total of 101 anterior STEMI patients (31 female, 70 male) and 34 TTS patients (29 female, 5 male) were included. The temporal pattern of T wave inversion was similar between female anterior STEMI and female TTS, as well as between female and male anterior STEMI. ST elevation was more common, whereas QT prolongation was less common, in anterior STEMI compared with TTS. Q wave pathology was more similar between female anterior STEMI and female TTS than between female and male anterior STEMI.The pattern of T wave inversion and Q wave pathology from admission to day 30 was similar in female patients with anterior STEMI and female patients with TTS. Temporal ECG in female patients with TTS may be interpreted as following a "transient ischemic" pattern.
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| 14. |
- Zeijlon, Rickard, et al.
(författare)
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The role of admission electrocardiogram in predicting outcome in patients hospitalized for COVID-19.
- 2022
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Ingår i: Journal of electrocardiology. - : Elsevier BV. - 0022-0736 .- 1532-8430. ; 75, s. 10-18
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Tidskriftsartikel (refereegranskat)abstract
- Abnormal electrocardiogram (ECG) has been associated with poor outcome in patients hospitalized for COVID-19. However, the independent association between admission ECG and the risk of a poor outcome remains to be established. Our aim was to determine if abnormal admission ECG predicts treatment at intensive care unit or in-hospital death within 30days in patients hospitalized for COVID-19.We analyzed the propensity weighted association between abnormal admission ECG and outcome in patients hospitalized for COVID-19 (March to May 2020). All adult patients hospitalized for COVID-19 at the three centers of Sahlgrenska University Hospital (Gothenburg, Sweden) were eligible for inclusion (N=439). Patients with available admission ECG within six hours from admission were included.238 patients (age 62±16years, 74% male) were included. 103 patients had normal ECG and 135 patients had abnormal ECG. 99 patients were admitted to intensive care unit or died in-hospital within 30days. Abnormal ECG was associated with increased risk of the outcome (odds ratio 2.11 [95% confidence interval 1.21-3.66]).Abnormal admission ECG was associated with increased risk of treatment at intensive care unit or in-hospital death within 30days; and could be considered a high-risk criterion in patients hospitalized for COVID-19.
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