| 1. |
- Glodzik, Dominik, et al.
(författare)
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Comprehensive molecular comparison of BRCA1 hypermethylated and BRCA1 mutated triple negative breast cancers
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Homologous recombination deficiency (HRD) is a defining characteristic in BRCA-deficient breast tumors caused by genetic or epigenetic alterations in key pathway genes. We investigated the frequency of BRCA1 promoter hypermethylation in 237 triple-negative breast cancers (TNBCs) from a population-based study using reported whole genome and RNA sequencing data, complemented with analyses of genetic, epigenetic, transcriptomic and immune infiltration phenotypes. We demonstrate that BRCA1 promoter hypermethylation is twice as frequent as BRCA1 pathogenic variants in early-stage TNBC and that hypermethylated and mutated cases have similarly improved prognosis after adjuvant chemotherapy. BRCA1 hypermethylation confers an HRD, immune cell type, genome-wide DNA methylation, and transcriptional phenotype similar to TNBC tumors with BRCA1-inactivating variants, and it can be observed in matched peripheral blood of patients with tumor hypermethylation. Hypermethylation may be an early event in tumor development that progress along a common pathway with BRCA1-mutated disease, representing a promising DNA-based biomarker for early-stage TNBC.
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| 2. |
- van de Vegte, Yordi, et al.
(författare)
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Genetic insights into resting heart rate and its role in cardiovascular disease
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
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| 3. |
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| 4. |
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| 5. |
- Baldanzi, Gabriel, et al.
(författare)
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OSA Is Associated With the Human Gut Microbiota Composition and Functional Potential in the Population-Based Swedish CardioPulmonary bioImage Study
- 2023
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Ingår i: Chest. - : Elsevier. - 0012-3692 .- 1931-3543. ; 164:2, s. 503-516
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent hypoxia and intermittent airway obstruction, hallmarks of OSA, have been shown in animal models to induce substantial changes to the gut microbiota composition and subsequent transplantation of fecal matter to other animals induced changes in blood pressure and glucose metabolism.RESEARCH QUESTION: Does obstructive sleep apnea in adults associate with the composition and metabolic potential of the human gut microbiota?STUDY DESIGN AND METHODS: We used respiratory polygraphy data from up to 3,570 individuals aged 50-64 from the population-based Swedish CardioPulmonary bioImage Study combined with deep shotgun metagenomics of fecal samples to identify cross-sectional associations between three OSA parameters covering apneas and hypopneas, cumulative sleep time in hypoxia and number of oxygen desaturation events with gut microbiota composition. Data collection about potential confounders was based on questionnaires, on-site anthropometric measurements, plasma metabolomics, and linkage with the Swedish Prescribed Drug Register.RESULTS: We found that all three OSA parameters were associated with lower diversity of species in the gut. Further, the OSA-related hypoxia parameters were in multivariable-adjusted analysis associated with the relative abundance of 128 gut bacterial species, including higher abundance of Blautia obeum and Collinsela aerofaciens. The latter species was also independently associated with increased systolic blood pressure. Further, the cumulative time in hypoxia during sleep was associated with the abundance of genes involved in nine gut microbiota metabolic pathways, including propionate production from lactate. Lastly, we observed two heterogeneous sets of plasma metabolites with opposite association with species positively and negatively associated with hypoxia parameters, respectively.INTERPRETATION: OSA-related hypoxia, but not the number of apneas/hypopneas, is associated with specific gut microbiota species and functions. Our findings lay the foundation for future research on the gut microbiota-mediated health effects of OSA.
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| 6. |
- Bhiladvala, Pallonji, et al.
(författare)
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Early identification of acute myocardial infarction by activated protein C-protein C inhibitor complex.
- 2006
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Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 118:Aug 10, s. 213-219
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Increased coagulation activity due to coronary thrombosis in a ruptured plaque should result in activation of the protein C anticoagulant system with formation of complexes between activated protein C (APC) and,the protein C inhibitor (PCI), which reflects coagulation activity. We hypothesized that elevated APC-PCI concentration might allow earlier detection of ongoing myocardial infarction than traditional biochemical markers. We have evaluated a newly devised immunofluorimetric assay for measuring plasma concentration of APC-PCI complexes among patients with suspected acute coronary syndrome. Materials and methods: Blood samples were taken from 340 patients (median 71 years, range 31-97) with suspected acute coronary syndrome at first presentation in the emergency department. Electrocardiogram was recorded and APC PCI, Troponin I and Creatine kinase-MB concentrations were repeatedly measured 3 times at 6 h interval. Results: The 74 patients who were eventually diagnosed with myocardial infarction had a higher median level of APC-PCI complex than those Without myocardial damage; 0.27 vs. 0.20 mu g/L (p = 0.001). In a multivariate regression model, APC-PCI level in the fourth quartile (> 0.32 mu g/L) independently predicted myocardial infarction with an odds ratio of 3.7 (95% CI 1.4-9.6, p < 0.01). Conclusion: Early APC-PCI elevation can be detected among patients with a normal first Troponin I and non-ST-elevation myocardial infarction and provides additional risk assessment in acute coronary syndrome. (c) 2005 Published by Elsevier Ltd.
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| 7. |
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Bioblitz i Arkelstorp 16-17 augusti 2019
- 2020
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Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- Arkelstorpsviken är den nordvästra delen av Oppmannasjön, som ären av Skånes största sjöar. Idén att genomföra en så kallad Bioblitzvid Arkelstorpsviken föddes under ett styrelsemöte i projektet "En viki Sjöriket Skåne" som är ett samarbete mellan Oppmanna Vånga Bygderåd och Högskolan Kristianstad. Projektets främsta syfte är att hitta en lösning på den kraftiga övergödningen i Arkelstorpsviken. Detta är ett ”Leader”-finansierat projekt, vilket innebär att stommen i projektetär lokal förankring. Det fanns röster i byn som kände att man gav området onödigt dåligt rykte genom att ständigt lyfta fram problemen med vattenstatusen i sjön. Under ett styrelsemöte 30 sep 2018 föddes iden att genom en Bioblitz lyfta fram de positiva värdena i och kring sjön. Den naturliga samarbetspartnern för detta projekt var forskningsmiljön MABH (Man & Biosphere Health) vid Högskolan Kristianstad,vars medlemmar tillsammans besitter en mycket bred biologisk kunskap.Med MABH i ryggen var alltså kompetensen säkrad för att genomföra en Bioblitz. Inbjudningar skickades ut till lokala naturorganisationerför att hitta ännu fler experter som kunde hjälpa till med särskilda artgrupper. Samtidigt jobbade man aktivt lokalt med att försöka engagera intresserad allmänhet. Inbjudningar och direktreklam skickades ut till samtliga hushåll med postadress Arkelstorp. I ett försök att synas genom mediebruset anordnades en tävling, som gick ut på att gissa antalet arter (taxa) som hittades under Bioblitzen. Två lokala företag ställde upp och första priset för den vuxna individ som gissade närmstvar en 3-rätters måltid på Bäckaskogs Slott. De yngre tävlande kunde vinna en kanotutflykt med familjen på Ivögården.
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| 8. |
- Bäcklund, Johan, et al.
(författare)
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Glycosylation of type II collagen is of major importance for T cell tolerance and pathology in collagen-induced arthritis.
- 2002
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Ingår i: European Journal of Immunology. - 1521-4141. ; 32:12, s. 3776-3784
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Tidskriftsartikel (refereegranskat)abstract
- Type II collagen (CII) is a candidate cartilage-specific autoantigen, which can become post-translationally modified by hydroxylation and glycosylation. T cell recognition of CII is essential for the development of murine collagen-induced arthritis (CIA) and also occurs in rheumatoid arthritis (RA). The common denominator of murine CIA and human RA is the presentation of an immunodominant CII-derived glycosylated peptide on murine Aq and human DR4 molecules, respectively. To investigate the importance of T cell recognition of glycosylated CII in CIA development after immunization with heterologous CII, we treated neonatal mice with different heterologous CII-peptides (non-modified, hydroxylated and galactosylated). Treatment with the galactosylated peptide (galactoseat position 264) was superior in protecting mice from CIA. Protection was accompanied by a reduced antibody response to CII and by an impaired T cell response to the glycopeptide. To investigate the importance of glycopeptide recognition in an autologous CIA model, we treated MMC-transgenic mice, which express the heterologous CII epitope with a glutamic acid in position 266 in cartilage, with CII-peptides. Again, a strong vaccination potential of the glycopeptide was seen. Hence CII-glycopeptides may be the optimal choice of vaccination target in RA, since humans share the same epitope as the MMC mouse
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| 9. |
- Dekkers, Koen, et al.
(författare)
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An online atlas of human plasma metabolite signatures of gut microbiome composition.
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Human gut microbiota produce a variety of molecules, some of which enter the bloodstream and impact health. Conversely, dietary or pharmacological compounds may affect the microbiota before entering the circulation. Characterization of these interactions is an important step towards understanding the effects of the gut microbiota on health. In this cross-sectional study, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for a detailed characterization of the gut microbiota and plasma metabolome, respectively, of 8583 participants invited at age 50 to 64 from the population-based Swedish CArdioPulmonary bioImage Study. Here, we find that the gut microbiota explain up to 58% of the variance of individual plasma metabolites and we present 997 associations between alpha diversity and plasma metabolites and 546,819 associations between specific gut metagenomic species and plasma metabolites in an online atlas ( https://gutsyatlas.serve.scilifelab.se/ ). We exemplify the potential of this resource by presenting novel associations between dietary factors and oral medication with the gut microbiome, and microbial species strongly associated with the uremic toxin p-cresol sulfate. This resource can be used as the basis for targeted studies of perturbation of specific metabolites and for identification of candidate plasma biomarkers of gut microbiota composition.
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| 10. |
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| 11. |
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| 12. |
- Etminani, Farzaneh, 1984-, et al.
(författare)
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Randomised, siteless study to compare systematic atrial fibrillation screening using enrichment by a risk prediction model with standard care in a Swedish population aged ≥ 65 years : CONSIDERING-AF study design
- 2024
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Ingår i: BMJ Open. - London : BMJ Publishing Group Ltd. - 2044-6055. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Atrial fibrillation (AF) is the most common arrhythmia and confers an increased risk of mortality, stroke, heart failure and cognitive decline. There is growing interest in AF screening; however, the most suitable population and device for AF detection remains to be elucidated. Here, we present the design of the CONSIDERING-AF (deteCtiON and Stroke preventIon by moDEl scRreenING for Atrial Fibrillation) study. METHODS AND ANALYSIS: CONSIDERING-AF is a randomised, controlled, siteless, non-blinded diagnostic superiority trial with four parallel groups and a primary endpoint of identifying AF during a 6-month study period set in Region Halland, Sweden. In each group, 740 individuals aged≥65 years will be included. The primary objective is to compare the intervention of AF screening enrichment using a risk prediction model (RPM), followed by 14 days of a continuous ECG patch, with no intervention (standard care). Primary outcome is defined as the incident AF recorded in the Region Halland Information Database after 6 months as compared with standard care. Secondary endpoints include the difference in incident AF between groups enriched or not by the RPM, with and without an invitation to 14 days of continuous ECG recording, and the proportions of oral anticoagulation treatment in the four groups. ETHICS AND DISSEMINATION: This study has ethical approval from the Swedish Ethical Review Authority. Results will be published in peer-reviewed international journals. TRIAL REGISTRATION NUMBER: NCT05838781. © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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| 13. |
- Gedda, Christer, et al.
(författare)
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Grundvattenvärme : kvarteret Tärnan i Landskrona
- 1989
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Rapporten redovisar fältförsök, uppföljning och termohydraulisk utvärdering av en experimentbyggnadsanläggning i kvarteret Tärnan i Landskrona. En låg energiförbrukning eftersträvas genom överglasad gata m.m.
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| 14. |
- Guillemain, Matthieu, et al.
(författare)
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Effects of climate change on European ducks : what do we know and what do we need to know?
- 2013
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Ingår i: Wildlife Biology. - : Nordic Council of Wildlife Research. - 0909-6396 .- 1903-220X. ; 19:4, s. 404-419
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Tidskriftsartikel (refereegranskat)abstract
- The consequences of climate change for bird populations have received much attention in recent decades, especially amongst cavity-nesting songbirds, yet little has been written on ducks (Anatidae) despite these being major elements of wetland diversity and important quarry species. This paper reviews the major known consequences of climate change for birds in general, and relates these to the limited information available specifically for ducks. Climate change can influence migration distance and phenology, potentially affecting patterns of mortality, as well as distribution and reproductive success in ducks. Studies addressing effects of climate change are, however, restricted to very few duck species, including mallardAnas platyrhynchos and common eider Somateria mollissima. Shifts in winter duck distributions have been observed, whereas the mismatch hypothesis (mistiming between the periods of peak energy requirements for young and the peak of seasonal food availability) has received limited support with regard to ducks. We propose a range of monitoring initiatives, including population surveys, breeding success monitoring schemes and individual duck marking, which should later be integrated through population modelling and adaptive management to fill these gaps.
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| 15. |
- Herlitz, Johan, 1949, et al.
(författare)
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Effect of fixed low-dose warfarin added to aspirin in the long term after acute myocardial infarction; the LoWASA Study
- 2004
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Ingår i: Eur Heart J. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 25:3, s. 232-9
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To evaluate whether long-term treatment with a fixed low dose of warfarin in combination with aspirin improves the prognosis compared with aspirin treatment alone after an acute myocardial infarction (AMI). METHODS: Patients who were hospitalized for AMI were randomized to either 1.25mg of warfarin plus 75mg of aspirin (n=1659) daily or 75mg of aspirin alone (n=1641). The study was performed according to the PROBE (Prospective Open Treatment and Blinded End Point Evaluation) design and was conducted at 31 hospitals in Sweden. The median follow-up time was 5.0 years. In the aspirin+warfarin group, 30.2% were permanently withdrawn as opposed to 14.0% in the aspirin group (P<0.0001). Analyses were performed on an intention-to-treat basis. RESULTS: The combination of cardiovascular death, reinfarction or stroke was registered in 28.1% in the aspirin+warfarin group versus 28.8% in the aspirin group (NS). Cardiovascular deaths occurred in 14.2% in the aspirin+warfarin group vs 15.7% in the aspirin group (NS). Whereas no difference was found with regard to total mortality or reinfarction, those randomized to aspirin+warfarin had a reduced occurrence of stroke (4.7% vs 7.1%; P=0.004). The percentage of patients who suffered a serious bleed was 1.0% in the aspirin group vs 2.2% in the combination group (P=0.0006). CONCLUSION: A fixed low dose of warfarin added to aspirin in the long term after AMI did not reduce the combined risk of cardiovascular death, reinfarction or stroke. The results did, however, indicate that a fixed low dose of warfarin added to aspirin reduced the risk of stroke, but this was a secondary end point. The combination of aspirin and warfarin was associated with an increased risk of bleeding.
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| 16. |
- Herlitz, Johan, 1949, et al.
(författare)
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Factors associated with development of stroke long-term after myocardial infarction: experiences from the LoWASA trial
- 2005
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Ingår i: J Intern Med. - : Wiley. - 0954-6820 .- 1365-2796. ; 257:2, s. 201-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To describe factors associated with the development of stroke during long-term follow-up after acute myocardial infarction (AMI) in the LoWASA trial. PATIENTS: Patients who had been hospitalized for AMI were randomized within 42 days to receive either warfarin 1.25 mg plus aspirin 75 mg daily or aspirin 75 mg alone. DESIGN: The study was performed according to the probe design, that is open treatment and blinded end-point evaluation. SETTING: The study was performed in 31 hospitals in Sweden. The mean follow-up time was 5.0 years with a range of 1.7-6.7 years. RESULTS: In all, 3300 patients were randomized in the trial, of which 194 (5.9%) developed stroke (4.2% nonhaemorrhagic, 0.5% haemorrhagic and 1.3% uncertain. The following factors appeared as independent predictors for an increased risk of stroke: age, hazard ratio and 95% confidence interval (1.07; 1.05-1.08), a history of diabetes mellitus (2.4; 1.8-3.4), a history of stroke (2.3; 1.5-3.5), a history of hypertension (2.0; 1.5-2.7) and a history of smoking (1.5;1.1-2.0). Most of these factors were also predictors of a nonhaemorrhagic stroke whereas no predictor of haemorrhagic stroke was found. CONCLUSION: Risk indicators for stroke long-term after AMI were increasing age, a history of either diabetes mellitus, stroke, hypertension or smoking.
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| 17. |
- Holm, Astrid, et al.
(författare)
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Cohort study of the characteristics and outcomes in patients with COVID-19 and in-hospital cardiac arrest
- 2021
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- Objective We studied characteristics, survival, causes of cardiac arrest, conditions preceding cardiac arrest, predictors of survival and trends in the prevalence of COVID-19 among in-hospital cardiac arrest (IHCA) cases.Design and setting Registry-based observational study.Participants We studied all cases (>= 18 years of age) of IHCA receiving cardiopulmonary resuscitation in the Swedish Registry for Cardiopulmonary Resuscitation during 15 March 2020 to 31 December 2020. A total of 1613 patients were included and divided into the following groups: ongoing infection (COVID-19+; n=182), no infection (COVID-19-; n=1062) and unknown/not assessed (n=369).Main outcomes and measures We studied monthly trends in proportions of COVID-19 associated IHCAs, causes of IHCA in relation to COVID-19 status, clinical conditions preceding the cardiac arrest and predictors of survival.Results The rate of COVID-19+ patients suffering an IHCA increased to 23% during the first pandemic wave (April), then abated to 3% in July, and then increased to 19% during the second wave (December). Among COVID-19+ cases, 43% had respiratory insufficiency or infection as the underlying cause of the cardiac arrest, compared with 18% among COVID-19- cases. The most common clinical sign preceding cardiac arrest was hypoxia (57%) among COVID-19+ cases. OR for 30-day survival for COVID-19+ cases was 0.50 (95% CI 0.33 to 0.76), compared with COVID-19- cases.Conclusion During pandemic peaks, up to one-fourth of all IHCAs are complicated by COVID-19, and these patients have halved chance of survival, with women displaying the worst outcomes.
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| 18. |
- Holm, Adolf
(författare)
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Dissertatio, fata libertatis patriæ, sistens, cujus partem secundam, ... in Upsaliensis Athenæi auditorio Carol. majori, publice defensitare connituntur mag. Adolphus Holm, ... Nec non Johannes Carolus Höjer, Uplandi. Die 25 maji, a. 1771., P. 2
- 1771
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
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| 19. |
- Holm, Alexander, et al.
(författare)
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Patients' perspective on prostatic artery embolization : A qualitative study
- 2021
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Ingår i: SAGE Open Medicine. - : SAGE Open. - 2050-3121. ; 9, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim was to describe the patients' experience of undergoing prostatic artery embolization.Methods: A retrospective qualitative interview study was undertaken with 15 patients of mean age 73 years who had undergone prostatic artery embolization with a median duration of 210 min at two medium sized hospitals in Sweden. The reasons for conducting prostatic artery embolization were clean intermittent catheterization (n = 4), lower urinary tract symptoms (n = 10) or haematuria (n = 1). Data were collected through individual, semi-structured telephone interviews 1-12 months after treatment and analysed using qualitative content analysis.Results: Four categories with sub-categories were formulated to describe the results: a diverse experience; ability to control the situation; resumption of everyday activities and range of opinions regarding efficacy of outcomes. Overall, the patients described the procedure as painless, easy and interesting and reported that while the procedure can be stressful, a calm atmosphere contributed to achieving a good experience. Limitations on access to reliable information before, during and after the procedure were highlighted as a major issue. Practical ideas for improving patient comfort during the procedure were suggested. Improved communications between treatment staff and patients were also highlighted. Most patients could resume everyday activities, some felt tired and bruising caused unnecessary worry for a few. Regarding functional outcome, some patients described substantial improvement in urine flow while others were satisfied with regaining undisturbed night sleep. Those with less effect were considering transurethral resection of the prostate as a future option. Self-enrolment to the treatment and long median operation time may have influenced the results.Conclusions: From the patients' perspective, prostatic artery embolization is a well-tolerated method for treating benign prostate hyperplacia.
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| 20. |
- Holm, Fanny, 1980-, et al.
(författare)
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Vem ska skydda politikerna? Ett fragmenterat rättsligt skydd för förtroendevalda som möter hot och våld
- 2024
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Ingår i: Svensk Juristtidning. - Stockholm : Svensk juristtidning. - 0039-6591. ; , s. 421-438
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Tidskriftsartikel (refereegranskat)abstract
- Våld, hot och trakasserier mot förtroendevalda på grund av deras politiska uppdrag är ett allvarligt problem, både för den individ som utsätts och för det demokratiska systemet. Artikeln undersöker vilket ansvar som åvilar olikaaktörer att ge förtroendevalda skydd mot brottsutsatthet och stöd när brott har begåtts. En analys av det rättsliga ramverket visar att förtroendevalda om-fattas av generella regler för brottsoffer, men att aktörernas ansvar för olika kategorier av politiker skiljer sig åt, och att det mer omfattande förebyggande arbete som arbetsmiljölagstiftningen tar sikte på, inte gäller denna grupp. Författarna efterlyser en översyn av det rättsliga ramverket i syfte att åstadkomma likvärdigt skydd och stöd för alla förtroendevalda.
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| 21. |
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| 22. |
- Holm, Karolina, et al.
(författare)
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Characterisation of amplification patterns and target genes at chromosome 11q13 in CCND1-amplified sporadic and familial breast tumours.
- 2012
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 133:2, s. 583-594
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Tidskriftsartikel (refereegranskat)abstract
- Amplification of chromosomal region 11q13, containing the cell cycle regulatory gene CCND1, is frequently found in breast cancer and other malignancies. It is associated with the favourable oestrogen receptor (ER)-positive breast tumour phenotype, but also with poor prognosis and treatment failure. 11q13 spans almost 14 Mb and contains more than 200 genes and is affected by various patterns of copy number gains, suggesting complex mechanisms and selective pressure during tumour progression. In this study, we used 32 k tiling BAC array CGH to analyse 94 CCND1-amplified breast tumours from sporadic, hereditary, and familial breast cancers to fine map chromosome 11q13. A set containing 281 CCND1-non-amplified breast tumours was used for comparisons. We used gene expression data to further validate the functional effect of gene amplification. We identified six core regions covering 11q13.1-q14.1 that were amplified in different combinations. The major core contained CCND1, whereas two cores were found proximal of CCND1 and three distal. The majority of the CCND1-amplified tumours were ER-positive and classified as luminal B. Furthermore, we found that CCND1 amplification is associated with a more aggressive phenotype within histological grade 2 tumours and luminal A subtype tumours. Amplification was equally prevalent in familial and sporadic tumours, but strikingly rare in BRCA1- and BRCA2-mutated tumours. We conclude that 11q13 includes many potential target genes in addition to CCND1.
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| 23. |
- Holm, Karolina, et al.
(författare)
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Molecular subtypes of breast cancer are associated with characteristic DNA methylation patterns
- 2010
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Five different molecular subtypes of breast cancer have been identified through gene expression profiling. Each subtype has a characteristic expression pattern suggested to partly depend on cellular origin. We aimed to investigate whether the molecular subtypes also display distinct methylation profiles. Methods: We analysed methylation status of 807 cancer-related genes in 189 fresh frozen primary breast tumours and four normal breast tissue samples using an array-based methylation assay. Results: Unsupervised analysis revealed three groups of breast cancer with characteristic methylation patterns. The three groups were associated with the luminal A, luminal B and basal-like molecular subtypes of breast cancer, respectively, whereas cancers of the HER2-enriched and normal-like subtypes were distributed among the three groups. The methylation frequencies were significantly different between subtypes, with luminal B and basal-like tumours being most and least frequently methylated, respectively. Moreover, targets of the polycomb repressor complex in breast cancer and embryonic stem cells were more methylated in luminal B tumours than in other tumours. BRCA2-mutated tumours had a particularly high degree of methylation. Finally, by utilizing gene expression data, we observed that a large fraction of genes reported as having subtype-specific expression patterns might be regulated through methylation. Conclusions: We have found that breast cancers of the basal-like, luminal A and luminal B molecular subtypes harbour specific methylation profiles. Our results suggest that methylation may play an important role in the development of breast cancers.
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| 24. |
- Jönsson, Göran B, et al.
(författare)
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Genomic subtypes of breast cancer identified by array-comparative genomic hybridization display distinct molecular and clinical characteristics
- 2010
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Breast cancer is a profoundly heterogeneous disease with respect to biologic and clinical behavior. Gene-expression profiling has been used to dissect this complexity and to stratify tumors into intrinsic gene-expression subtypes, associated with distinct biology, patient outcome, and genomic alterations. Additionally, breast tumors occurring in individuals with germline BRCA1 or BRCA2 mutations typically fall into distinct subtypes. Methods: We applied global DNA copy number and gene-expression profiling in 359 breast tumors. All tumors were classified according to intrinsic gene-expression subtypes and included cases from genetically predisposed women. The Genomic Identification of Significant Targets in Cancer (GISTIC) algorithm was used to identify significant DNA copy-number aberrations and genomic subgroups of breast cancer. Results: We identified 31 genomic regions that were highly amplified in > 1% of the 359 breast tumors. Several amplicons were found to co-occur, the 8p12 and 11q13.3 regions being the most frequent combination besides amplicons on the same chromosomal arm. Unsupervised hierarchical clustering with 133 significant GISTIC regions revealed six genomic subtypes, termed 17q12, basal-complex, luminal-simple, luminal-complex, amplifier, and mixed subtypes. Four of them had striking similarity to intrinsic gene-expression subtypes and showed associations to conventional tumor biomarkers and clinical outcome. However, luminal A-classified tumors were distributed in two main genomic subtypes, luminal-simple and luminal-complex, the former group having a better prognosis, whereas the latter group included also luminal B and the majority of BRCA2-mutated tumors. The basal-complex subtype displayed extensive genomic homogeneity and harbored the majority of BRCA1-mutated tumors. The 17q12 subtype comprised mostly HER2-amplified and HER2-enriched subtype tumors and had the worst prognosis. The amplifier and mixed subtypes contained tumors from all gene-expression subtypes, the former being enriched for 8p12-amplified cases, whereas the mixed subtype included many tumors with predominantly DNA copy-number losses and poor prognosis. Conclusions: Global DNA copy-number analysis integrated with gene-expression data can be used to dissect the complexity of breast cancer. This revealed six genomic subtypes with different clinical behavior and a striking concordance to the intrinsic subtypes. These genomic subtypes may prove useful for understanding the mechanisms of tumor development and for prognostic and treatment prediction purposes.
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| 25. |
- Jönsson, Göran B, et al.
(författare)
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The retinoblastoma gene undergoes rearrangements in BRCA1-deficient basal-like breast cancer.
- 2012
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Ingår i: Cancer Research. - 1538-7445. ; 72:16, s. 4028-4036
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Tidskriftsartikel (refereegranskat)abstract
- Breast tumors from BRCA1 germ line mutation carriers typically exhibit features of the basal-like molecular subtype. However, the specific genes recurrently mutated as a consequence of BRCA1 dysfunction have not been fully elucidated. In this study, we utilized gene expression profiling to molecularly subtype 577 breast tumors, including 72 breast tumors from BRCA1/2 mutation carriers. Focusing on the RB1 locus, we analyzed 33 BRCA1-mutated, 36 BRCA2-mutated and 48 non-BRCA1/2-mutated breast tumors using a custom-designed high-density oligomicroarray covering the RB1 gene. We found a strong association between the basal-like subtype and BRCA1-mutated breast tumors and the luminal B subtype and BRCA2-mutated breast tumors. RB1 was identified as a major target for genomic disruption in tumors arising in BRCA1 mutation carriers and in sporadic tumors with BRCA1 promoter-methylation, but rarely in other breast cancers. Homozygous deletions, intragenic breaks, or microdeletions were found in 33% of BRCA1-mutant tumors, 36% of BRCA1 promoter-methylated basal-like tumors, 13% of non-BRCA1 deficient basal-like tumors, and 3% of BRCA2-mutated tumors. In conclusion, RB1 was frequently inactivated by gross gene disruption in BRCA1-related hereditary breast cancer and BRCA1-methylated sporadic basal-like breast cancer, but rarely in BRCA2-hereditary breast cancer and non-BRCA1-deficient sporadic breast cancers. Together, our findings demonstrate the existence of genetic heterogeneity within the basal-like breast cancer subtype that is based upon BRCA1-status.
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| 26. |
- Rydberg Sterner, Therese, et al.
(författare)
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The Gothenburg H70 Birth cohort study 2014-16: design, methods and study population.
- 2019
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Ingår i: European journal of epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 34:2, s. 191-209
-
Tidskriftsartikel (refereegranskat)abstract
- To improve health care for older persons, we need to learn more about ageing, e.g. identify protective factors and early markers for diseases. The Gothenburg H70 Birth Cohort Studies (the H70 studies) are multidisciplinary epidemiological studies examining representative birth cohorts of older populations in Gothenburg, Sweden. So far, six birth cohorts of 70-year-olds have been examined over time, and examinations have been virtually identical between studies. This paper describes the study procedures for the baseline examination of the Birth cohort 1944, conducted in 2014-16. In this study, all men and women born 1944 on specific dates, and registered as residents in Gothenburg, were eligible for participation (n=1839). A total of 1203 (response rate 72.2%; 559 men and 644 women; mean age 70.5years) agreed to participate in the study. The study comprised sampling of blood and cerebrospinal fluid, psychiatric, cognitive, and physical health examinations, examinations of genetics and family history, use of medications, social factors, functional ability and disability, physical fitness and activity, body composition, lung function, audiological and ophthalmological examinations, diet, brain imaging, as well as a close informant interview, and qualitative studies. As in previous examinations, data collection serves as a basis for future longitudinal follow-up examinations. The research gained from the H70 studies has clinical relevance in relation to prevention, early diagnosis, clinical course, experience of illness, understanding pathogenesis and prognosis. Results will increase our understanding of ageing and inform service development, which may lead to enhanced quality of care for older persons.
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| 27. |
- Saal, Lao, et al.
(författare)
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Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:1, s. 102-107
-
Tidskriftsartikel (refereegranskat)abstract
- Basal-like breast cancer (BBC) is a subtype of breast cancer with poor prognosis1, 2, 3. Inherited mutations of BRCA1, a cancer susceptibility gene involved in double-strand DNA break (DSB) repair, lead to breast cancers that are nearly always of the BBC subtype3, 4, 5; however, the precise molecular lesions and oncogenic consequences of BRCA1 dysfunction are poorly understood. Here we show that heterozygous inactivation of the tumor suppressor gene Pten leads to the formation of basal-like mammary tumors in mice, and that loss of PTEN expression is significantly associated with the BBC subtype in human sporadic and BRCA1-associated hereditary breast cancers. In addition, we identify frequent gross PTEN mutations, involving intragenic chromosome breaks, inversions, deletions and micro copy number aberrations, specifically in BRCA1-deficient tumors. These data provide an example of a specific and recurrent oncogenic consequence of BRCA1-dependent dysfunction in DNA repair and provide insight into the pathogenesis of BBC with therapeutic implications. These findings also argue that obtaining an accurate census of genes mutated in cancer will require a systematic examination for gross gene rearrangements, particularly in tumors with deficient DSB repair.
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| 28. |
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| 29. |
- Salihovic, Samira, Associate Senior Lecturer, 1985-, et al.
(författare)
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Identification and validation of a blood- based diagnostic lipidomic signature of pediatric inflammatory bowel disease
- 2024
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- Improved biomarkers are needed for pediatric inflammatory bowel disease. Here we identify a diagnostic lipidomic signature for pediatric inflammatory bowel disease by analyzing blood samples from a discovery cohort of incident treatment-naïve pediatric patients and validating findings in an independent inception cohort. The lipidomic signature comprising of only lactosyl ceramide (d18:1/16:0) and phosphatidylcholine (18:0p/22:6) improves the diagnostic prediction compared with high-sensitivity C-reactive protein. Adding high-sensitivity C-reactive protein to the signature does not improve its performance. In patients providing a stool sample, the diagnostic performance of the lipidomic signature and fecal calprotectin, a marker of gastrointestinal inflammation, does not substantially differ. Upon investigation in a third pediatric cohort, the findings of increased lactosyl ceramide (d18:1/16:0) and decreased phosphatidylcholine (18:0p/22:6) absolute concentrations are confirmed. Translation of the lipidomic signature into a scalable diagnostic blood test for pediatric inflammatory bowel disease has the potential to support clinical decision making.
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| 30. |
- Salihovic, Samira, Associate Senior Lecturer, 1985-, et al.
(författare)
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Identification and validation of a blood- based diagnostic lipidomic signature of pediatric inflammatory bowel disease
- 2024
-
Ingår i: Nature Communications. - : NATURE PORTFOLIO. - 2041-1723. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- Improved biomarkers are needed for pediatric inflammatory bowel disease. Here we identify a diagnostic lipidomic signature for pediatric inflammatory bowel disease by analyzing blood samples from a discovery cohort of incident treatment-na & iuml;ve pediatric patients and validating findings in an independent inception cohort. The lipidomic signature comprising of only lactosyl ceramide (d18:1/16:0) and phosphatidylcholine (18:0p/22:6) improves the diagnostic prediction compared with high-sensitivity C-reactive protein. Adding high-sensitivity C-reactive protein to the signature does not improve its performance. In patients providing a stool sample, the diagnostic performance of the lipidomic signature and fecal calprotectin, a marker of gastrointestinal inflammation, does not substantially differ. Upon investigation in a third pediatric cohort, the findings of increased lactosyl ceramide (d18:1/16:0) and decreased phosphatidylcholine (18:0p/22:6) absolute concentrations are confirmed. Translation of the lipidomic signature into a scalable diagnostic blood test for pediatric inflammatory bowel disease has the potential to support clinical decision making. Diagnostic blood-based biomarkers of pediatric IBD are limited. Here, the authors demonstrate a diagnostic lipidomic signature, comprising only of two molecular lipids. Translation of this signature into a scalable test has the potential to support clinical decision making.
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| 31. |
- Sayols-Baixeras, Sergi, et al.
(författare)
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Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort
- 2023
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 148:6, s. 459-472
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography-based measures of coronary atherosclerosis and to explore relevant clinical correlates.Methods: We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of stool, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva.Results: The mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for Streptococcus anginosus and Streptococcus oralis subsp oralis (P<1×10-5). Associations were largely similar across coronary computed tomography angiography-based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid β-oxidation, and amino acid degradation were associated with coronary artery calcium score.Conclusions: This study provides evidence of an association of a gut microbiota composition characterized by increased abundance of Streptococcus spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.
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| 32. |
- Sayols-Baixeras, Sergi, et al.
(författare)
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Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort
- 2023
-
Ingår i: Circulation. - : American Heart Association. - 0009-7322 .- 1524-4539. ; 148:6, s. 459-472
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography–based measures of coronary atherosclerosis and to explore relevant clinical correlates.METHODS: We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of fecal samples, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva.RESULTS: The mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for Streptococcus anginosus and Streptococcus oralis subsp oralis (P<1×10–5). Associations were largely similar across coronary computed tomography angiography–based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid β-oxidation, and amino acid degradation were associated with coronary artery calcium score.CONCLUSIONS: This study provides evidence of an association of a gut microbiota composition characterized by increased abundance of Streptococcus spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.
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| 33. |
- Sleincour, Johan Peter, 1714-1785
(författare)
-
Dissertatio, fata libertatis patriæ, sistens, cujus partem primam nutu incliti ordinis philosophici, in Upsaliensis athenæi auditorio Carol. majori, sub auspicio Mag. Joh. Petri Sleincour, ... Die 14. Martii, a. 1770. ... Stipend. Piper. Adolf. Car. Holm. Upl., p. 1
- 1770
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
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| 34. |
- Staaf, Johan, et al.
(författare)
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Identification of Subtypes in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Reveals a Gene Signature Prognostic of Outcome.
- 2010
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 28:11, s. 1813-1820
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Human epidermal growth factor receptor 2 (HER2) gene amplification or protein overexpression (HER2 positivity) defines a clinically challenging subgroup of patients with breast cancer (BC) with variable prognosis and response to therapy. We aimed to investigate the heterogeneous biologic appearance and clinical behavior of HER2-positive tumors using molecular profiling. PATIENTS AND METHODS: Hierarchical clustering of gene expression data from 58 HER2-amplified tumors of various stage, histologic grade, and estrogen receptor (ER) status was used to construct a HER2-derived prognostic predictor that was further evaluated in several large independent BC data sets. RESULTS: Unsupervised analysis identified three subtypes of HER2-positive tumors with mixed stage, histologic grade, and ER status. One subtype had a significantly worse clinical outcome. A prognostic predictor was created based on differentially expressed genes between the subtype with worse outcome and the other subtypes. The predictor was able to define patient groups with better and worse outcome in HER2-positive BC across multiple independent BC data sets and identify a sizable HER2-positive group with long disease-free survival and low mortality. Significant correlation to prognosis was also observed in basal-like, ER-negative, lymph node-positive, and high-grade tumors, irrespective of HER2 status. The predictor included genes associated with immune response, tumor invasion, and metastasis. CONCLUSION: The HER2-derived prognostic predictor provides further insight into the heterogeneous biology of HER2-positive tumors and may become useful for improved selection of patients who need additional treatment with new drugs targeting the HER2 pathway.
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| 35. |
- Strandberg, K, et al.
(författare)
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A new method to measure plasma levels of activated protein C in complex with protein C inhibitor in patients with acute coronary syndromes
- 2001
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 12:7, s. 503-510
-
Tidskriftsartikel (refereegranskat)abstract
- Our newly devised immunofluorometric sandwich assay for measuring plasma concentrations of activated protein C (APC) in complex with protein C inhibitor (PCI) was compared with testing for conventional markers of myocardial damage CKMB (creatine kinase MB), TNI (troponin I) and hypercoagulability (D-dimer, TAT) in 76 patients with suspected myocardial infarction (MI). APC-PCI complex levels in samples drawn on admission did not correlate with CKMB in the simultaneously drawn sample but correlated closely with maximal CKMB, which reflects MI size (r = 0.52). The areas under the receiver operating characteristics (ROC) curves calculated for the APC-PCI complex results obtained upon admission did not differ significantly from the corresponding values for CKMB, TNI or TAT. Our results show that in patients at risk for MI, the APC-PCI concentration is a sensitive and independent marker that can identify a subgroup of MI patients with normal CKMB but an increased APC-PCI level upon admission. It remains to be determined whether these patients would benefit from early intensive anticoagulant treatment.
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| 36. |
- Abdi, Abdulhakim M., et al.
(författare)
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Biodiversity decline with increasing crop productivity in agricultural fields revealed by satellite remote sensing
- 2021
-
Ingår i: Ecological Indicators. - : Elsevier BV. - 1470-160X. ; 130
-
Tidskriftsartikel (refereegranskat)abstract
- Increasing land-use intensity is a main driver of biodiversity loss in farmland, but measuring proxies for land-use intensity across entire landscapes is challenging. Here, we develop a novel method for the assessment of the impact of land-use intensity on biodiversity in agricultural landscapes using remote sensing parameters derived from the Sentinel-2 satellites. We link crop phenology and productivity parameters derived from time-series of a two-band enhanced vegetation index with biodiversity indicators (insect pollinators and insect-pollinated vascular plants) in agricultural fields in southern Sweden, with contrasting land management (i.e. conventional and organic farming). Our results show that arable land-use intensity in cereal systems dominated by spring-sown cereals can be approximated using Sentinel-2 productivity parameters. This was shown by the significant positive correlations between the amplitude and maximum value of the enhanced vegetation index on one side and farmer reported yields on the other. We also found that conventional cereal fields had 17% higher maximum and 13% higher amplitude of their enhanced vegetation index than organic fields. Sentinel-2 derived parameters were more strongly correlated with the abundance and species richness of bumblebees and the richness of vascular plants than the abundance and species richness of butterflies. The relationships we found between biodiversity and crop production proxies are consistent with predictions that increasing agricultural land-use intensity decreases field biodiversity. The newly developed method based on crop phenology and productivity parameters derived from Sentinel-2 data serves as a proof of concept for the assessment of the impact of land-use intensity on biodiversity over cereal fields across larger areas. It enables the estimation of arable productivity in cereal systems, which can then be used by ecologists and develop tools for land managers as a proxy for land-use intensity. Coupled with spatially explicit databases on agricultural land-use, this method will enable crop-specific cereal productivity estimation across large geographical regions.
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| 37. |
- Abelev, Betty, et al.
(författare)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 38. |
- Abelev, Betty, et al.
(författare)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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| 39. |
- Abugabbara, Marwan, et al.
(författare)
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How to develop fifth-generation district heating and cooling in Sweden? : Application review and best practices proposed by middle agents
- 2023
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Ingår i: Energy Reports. - : Elsevier Ltd. - 2352-4847. ; 9, s. 4971-4983
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Tidskriftsartikel (refereegranskat)abstract
- Sweden has an ambitious plan to fully decarbonise district heating by 2030 and to contribute with negative emissions of greenhouse gases in 2050. The vagaries of the energy market associated with climate, political, and social changes entail cross-sectoral integration that can fulfill these national targets. Fifth-generation district heating and cooling (5GDHC) is a relatively new concept of district energy systems that features a simultaneous supply of heating and cooling using power-to-heat technologies. This paper presents best practices for developing 5GDHC systems in Sweden to reach a consensus view on these systems among all stakeholders. A mixed-method combining best practice and roadmapping workshops has been used to disseminate mixed knowledge and experience from middle agents representing industry professionals and practitioners. Four successful implementations of 5GDHC systems are demonstrated and the important learned lessons are shared. The best practices are outlined for system planning, system modeling and simulation, prevailing business models for energy communities, and system monitoring. A roadmap from the middle agents’ point of view is composed and can be utilised to establish industry standards and common regulatory frameworks. © 2023 The Author(s)
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| 40. |
- Ahti, Johan, et al.
(författare)
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Differences in psychosocial functioning between psychotic disorders in the Finnish SUPER study
- 2022
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Ingår i: Schizophrenia Research. - : Elsevier. - 0920-9964 .- 1573-2509. ; 244, s. 10-17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Psychotic disorders differ in their impact on psychosocial functioning. However, few studies have directly compared psychosocial functioning and its determinants between schizophrenia, schizoaffective disorder (SAD), bipolar disorder (BD), and major depressive disorder with psychotic features (psychotic MDD). Objective: We compared rates of independent living, employment, marriage, and having children between these diagnostic groups in a large national sample of participants with psychotic disorders in Finland.Methods: A cross-sectional substudy of participants (N = 9148) aged 18 to 65 years in the Finnish SUPER study, recruited nationwide from health- and social care settings and with advertisements. Psychosis diagnoses, age of onset, and hospitalizations were collected from healthcare registers. Participants were interviewed for psychosocial functioning. Associations of age of onset, hospitalizations, gender, and education with psychosocial functioning were analyzed using logistic regression models.Results: Of participants, 13.8% were employed or studying, 72.0% living independently and 32.5% had children. Overall, BD was associated with best, SAD and psychotic MDD with intermediate, and schizophrenia with worst level of psychosocial functioning. Greatest differences were found in independent living (OR 4.06 for BD vs. schizophrenia). In multivariate models, gender and number of hospitalizations predicted employment, marriage, and independent living in all diagnostic categories, and age of onset in some diagnostic categories.Conclusions: Level of functioning and psychosocial outcomes differed markedly between psychotic disorders, particularly in independent living. Outcomes were worst for schizophrenia and best for BD. Across all psychotic disorders, female gender and lifetime number of hospitalizations had strong independent associations with marriage, employment, and independent living.
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| 41. |
- Andersson, Johan, et al.
(författare)
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Cardiovascular responses to cold water immersions of the forearm and face, and their relationship to apnoea
- 2000
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Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 83:6, s. 566-572
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Tidskriftsartikel (refereegranskat)abstract
- Apnoea as well as cold stimulation of the face or the extremities elicits marked cardiovascular reflexes in humans. The purpose of this study was to investigate whether forearm immersion in cold water has any effect on the cardiovascular responses to face immersion and apnoea. We recorded cardiovascular responses to cold-water immersions of the forearm and face in 19 (part I) and 23 subjects (part II). The experimental protocol was divided in two parts, each part containing four tests: I1, forearm immersion during eupnoea; I2, face immersion during eupnoea; I3, forearm and face immersion during eupnoea; I4, face immersion during apnoea; II1, apnoea without immersion; II2, forearm immersion during apnoea; II3, face immersion during apnoea; and II4, forearm and face immersion during apnoea. The water temperature was 9–11 °C. Cold-water immersion of either the forearm or face was enough to elicit the most pronounced thermoregulatory vasoconstriction during both eupnoea and apnoea. During eupnoea, heart rate responses to forearm immersion (3% increase) and face immersion (9% decrease) were additive during concurrent stimulation (3% decrease). During apnoea, the heart rate responses were not affected by the forearm immersion. The oxygen-conserving diving response seems to dominate over thermoregulatory responses in the threat of asphyxia. During breathing, however, the diving response serves no purpose and does not set thermoregulatory adjustments aside
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| 42. |
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| 43. |
- Arking, D. E., et al.
(författare)
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Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
- 2014
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
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| 44. |
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| 45. |
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| 46. |
- Bengtsson, Caroline, et al.
(författare)
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Incident chronic rhinosinusitis is associated with impaired sleep quality: Results of the RhiNE study
- 2019
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Ingår i: Journal of Clinical Sleep Medicine. - : American Academy of Sleep Medicine (AASM). - 1550-9389 .- 1550-9397. ; 15:6, s. 899-905
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Tidskriftsartikel (refereegranskat)abstract
- Study Objectives: Chronic rhinosinusitis (CRS) is a common inflammatory disease of the nasal cavity and paranasal sinuses. Associations between CRS and poor sleep quality have been reported. This 10-year follow-up study investigates possible associations between incident CRS and sleep quality. Methods: A questionnaire was sent to 16,500 individuals in Sweden, Norway, Denmark, Iceland and Estonia in 2000. It included questions on airway diseases, age, sex, body mass index, smoking habits, comorbidities, education and sleep quality. In 2010, a second questionnaire was sent to the same individuals, with a response rate of 53%. A subgroup of 5,145 individuals without nasal symptoms in 2000 was studied. Multiple logistic regression was performed to examine associations between CRS (defined according to the European position paper on rhinosinusitis and nasal polyps epidemiological criteria) at follow-up and sleep quality, with adjustment for potential confounders. Individuals with the respective sleep problem at baseline were excluded. Results: Over 10 years, 141 (2.7%) of the individuals without nasal symptoms in 2000 had developed CRS. CRS was associated with difficulties inducing sleep (adjusted odds ratio 2.81 [95% CI 1.67–4.70]), difficulties maintaining sleep (2.07 [1.35–3.18]), early morning awakening (3.03 [1.91–4.81]), insomnia (2.21 [1.46–3.35]), excessive daytime sleepiness (2.85 [1.79–4.55]), and snoring (3.31 [2.07–5.31]). Three insomnia symptoms at baseline increased the risk of CRS at follow-up by 5.00 (1.93–12.99). Conclusions: Incident CRS is associated with impaired sleep quality and excessive daytime sleepiness. Insomnia symptoms may be a risk factor for the development of CRS. © 2019 American Academy of Sleep Medicine. All rights reserved.
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| 47. |
- Berglund, Sara, et al.
(författare)
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Cardiorenal function and survival in in-hospital cardiac arrest : A nationwide study of 22,819 cases
- 2022
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 172, s. 9-16
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Tidskriftsartikel (refereegranskat)abstract
- Background: We studied the association between cardiorenal function and survival, neurological outcome and trends in survival after in-hospital Methods: We included cases aged 18 years in the Swedish Cardiopulmonary Resuscitation Registry during 2008 to 2020. The CKD-EPI equation was used to calculate estimated glomerular filtration rate (eGFR). A history of heart failure was defined according to contemporary guideline criteria. Logistic regression was used to study survival. Neurological outcome was assessed using cerebral performance category (CPC). Results: We studied 22,819 patients with IHCA. The 30-day survival was 19.3%, 16.6%, 22.5%, 28.8%, 39.3%, 44.8% and 38.4% in cases with eGFR < 15, 15-29, 30-44, 45-59, 60-89, 90-130 and 130-150 ml/min/1.73 m2, respectively. All eGFR levels below and above 90 ml/min/1.73 m2 were associated with increased mortality. Probability of survival at 30 days was 62% lower in cases with eGFR < 15 ml/min/1.73 m2, compared with normal kidney function. At every level of eGFR, presence of heart failure increased mortality markedly; patients without heart failure displayed higher mortality only at eGFR below 30 ml/min/1.73 m2. Among survivors with eGFR < 15 ml/min/1.73 m2, good neurological outcome was noted in 87.2%. Survival increased in most groups over time, but most for those with eGFR < 15 ml/min/1.73 m2, and least for those with normal eGFR. Conclusions: All eGFR levels below and above normal range are associated with increased mortality and this association is modified by the presence of heart failure. Neurological outcome is good in the majority of cases, across kidney function levels and survival is increasing.
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| 48. |
- Berling Holm, Katarina, et al.
(författare)
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Surgery for chronic otitis media causes greater taste disturbance than surgery for otosclerosis
- 2019
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Ingår i: Otology and Neurotology. - : Lippincott Williams & Wilkins. - 1531-7129 .- 1537-4505. ; 40:1, s. e32-e39
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Patients with otosclerosis more often complain about postoperative taste disturbance than patients with chronic otitis media, which seems paradoxical. We aim to investigate if and potentially why this seems to be the case, since the chorda tympani nerve (CTN) is thought to be severely traumatized less frequently during surgery in the former than in the latter.Study Design: Prospective cohort study.Setting: Department of Otorhinolaryngology at Hospital of Vastmanland, Vasteras, Sweden.Patients: Sixty-five adults undergoing primary middle ear surgery were included. Thirty-seven were operated on for chronic suppurative otitis media with or without cholesteatoma (CSOM) and 28 for otosclerosis.Interventions: Middle ear surgery due to otosclerosis or CSOM. Subjective and objective taste measurements and quality of life (QoL) questionnaire.Main Outcome Measures: Taste was assessed using electrogustometry (EGM) and the filter paper disc (FPD) method before and up to 1 year after surgery. Questionnaires on taste disturbance, including a visual analogue scale (VAS), and QoL were completed before and up to 1 year after surgery.Results: Subjective taste disturbance anytime during the 1-year follow-up were reported by 62 and 46%, respectively. The difference in EGM 1 week after surgery compared with preoperative EGM was significantly greater among CSOM patients than otosclerosis. One year postoperatively, the difference is non-significant.Conclusion: Surgery for CSOM causes greater initial and more long-lasting taste disturbances as compared with surgery for otosclerosis. One-year postoperative taste normalizes for both CSOM and otosclerosis patients according to VAS and EGM measurements. No real change in QoL was seen 1-year postoperatively.
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| 49. |
- Berling Holm, Katarina, et al.
(författare)
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Taste disturbance after stapes surgery : an evaluation of frequency, severity, duration, and quality-of-life
- 2017
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Ingår i: Acta Oto-Laryngologica. - : Taylor & Francis Group. - 0001-6489 .- 1651-2251. ; 37:1, s. 39-43
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Tidskriftsartikel (refereegranskat)abstract
- Conclusion: The incidence of taste disturbance after stapes surgery is high (61.9 %), whereas the majority (94.8 %) recovers within 1 year. More severe surgical nerve trauma caused more disturbance, implying that the nerve should be handled carefully during surgery. Objectives: Patients operated on for otosclerosis seem more often to complain about post-operative taste disturbance than those operated on for chronic otitis media, although the chorda tympani nerve more seldom becomes maltreated in stapedotomy. These observations seem paradoxical. It is unclear to what extent a post-operative taste disturbance affects the quality-of-life. This study aims to shed light on the occurrence of post-operative taste disturbances, on possible prognostic factors, and to what extent post-operative taste disturbance impairs the quality-of-life. Methods: One hundred and thirty-four adults undergoing primary stapedotomy were included. Questionnaires on taste disturbance and quality-of-life (SF-36) were answered before and after surgery, until 1 year post-operatively. Results: Eighty-three (61.9%) study persons reported post-operative taste disturbance. Seven (5.2%) reported persisting disturbance at 1 year. Surgically more traumatized chorda tympani nerves correlated with more severe taste disturbance post-operatively than less traumatized. Taste disturbance at 1 year post-operatively correlate with a decrease of the physical function domain in the SF-36.
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| 50. |
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