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| 2. |
- Celik, Selvi, et al.
(författare)
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Extracellular Vesicle-Associated TWEAK Contributes to Vascular Inflammation and Remodeling During Acute Cellular Rejection
- 2023
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Ingår i: JACC: Basic to Translational Science. - : Elsevier BV. - 2452-302X. ; 8:5, s. 439-456
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Tidskriftsartikel (refereegranskat)abstract
- Acute cellular rejection (ACR) is a leading cause of graft loss and death after heart transplantation despite effective immunosuppressive therapies. The identification of factors that impair graft vascular barrier function or promote immune cell recruitment during ACR could provide new therapeutic opportunities for the treatment of patients who receive transplants. In 2 ACR cohorts, we found the extracellular vesicle-associated cytokine TWEAK to be elevated during ACR. Vesicular TWEAK promoted expression of proinflammatory genes and the release of chemoattractant cytokines from human cardiac endothelial cells. We conclude that vesicular TWEAK is a novel target with potential therapeutic implications in ACR.
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| 3. |
- Egerstedt, Anna, et al.
(författare)
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Bioactive adrenomedullin for assessment of venous congestion in heart failure
- 2022
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Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 9:5, s. 3543-3555
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Bioactive adrenomedullin (bio-ADM) is a vascular-derived peptide hormone that has emerged as a promising biomarker for assessment of congestion in decompensated heart failure (HF). We aimed to evaluate diagnostic and prognostic performance of bio-ADM for HF in comparison to amino-terminal pro-B-type natriuretic peptide (NT-proBNP), with decision thresholds derived from invasive haemodynamic and population-based studies. Methods and results: Normal reference ranges for bio-ADM were derived from a community-based cohort (n = 5060). Correlations with haemodynamic data were explored in a cohort of HF patients undergoing right heart catheterization (n = 346). Mortality and decision cutoffs for bio-ADM was explored in a cohort of patients presenting in the ER with acute dyspnoea (n = 1534), including patients with decompensated HF (n = 570). The normal reference range was 8–39 pg/mL. The area under the receiver operating characteristic curve (AUROC) for discrimination of elevated mean right atrial pressure (mRAP) and pulmonary arterial wedge pressure (PAWP) was 0.74 (95% CI = 0.67–0.79) and 0.70 (95% CI = 0.64–0.75), respectively, with optimal bio-ADM decision cutoff of 39 pg/mL, concordant with cubic spline analyses. NT-proBNP discriminated PAWP slightly better than mRAP (AUROC 0.73 [95% CI = 0.68–0.79] and 0.68 [95% CI = 0.61–0.75]). Bio-ADM correlated with (mRAP, r = 0.55) while NT-proBNP correlated with PAWP. Finally, a bio-ADM decision cutoff of 39 pg/mL associated with 30 and 90 day mortality and conferred a two-fold increased odds of HF diagnosis, independently from NT-proBNP. Conclusions: Bio-ADM tracks with mRAP and associates with measures of systemic congestion and with mortality in decompensated HF independently from NT-proBNP. Our findings support utility of bio-ADM as a biomarker of systemic venous congestion in HF and nominate a decision threshold.
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| 4. |
- Ghosh, Nilanjana, et al.
(författare)
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Analysis of plasma metabolomes from 11 309 subjects in five population-based cohorts.
- 2024
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Ingår i: Scientific Reports. - 2045-2322. ; 14:1, s. 8933-
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Tidskriftsartikel (refereegranskat)abstract
- Plasma metabolomics holds potential for precision medicine, but limited information is available to compare the performance of such methods across multiple cohorts. We compared plasma metabolite profiles after an overnight fast in 11,309 participants of five population-based Swedish cohorts (50-80 years, 52% women). Metabolite profiles were uniformly generated at a core laboratory (Metabolon Inc.) with untargeted liquid chromatography mass spectrometry and a comprehensive reference library. Analysis of a second sample obtained one year later was conducted in a subset. Of 1629 detected metabolites, 1074 (66%) were detected in all cohorts while only 10% were unique to one cohort, most of which were xenobiotics or uncharacterized. The major classes were lipids (28%), xenobiotics (22%), amino acids (14%), and uncharacterized (19%). The most abundant plasma metabolome components were the major dietary fatty acids and amino acids, glucose, lactate and creatinine. Most metabolites displayed a log-normal distribution. Temporal variability was generally similar to clinical chemistry analytes but more pronounced for xenobiotics. Extensive metabolite-metabolite correlations were observed but mainly restricted to within each class. Metabolites were broadly associated with clinical factors, particularly body mass index, sex and renal function. Collectively, our findings inform the conduct and interpretation of metabolite association and precision medicine studies.
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| 5. |
- Ghosh, Nilanjana, et al.
(författare)
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Analysis of plasma metabolomes from 11 309 subjects in five population-based cohorts.
- 2024
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Ingår i: Scientific Reports. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Plasma metabolomics holds potential for precision medicine, but limited information is available to compare the performance of such methods across multiple cohorts. We compared plasma metabolite profiles after an overnight fast in 11,309 participants of five population-based Swedish cohorts (50-80years, 52% women). Metabolite profiles were uniformly generated at a core laboratory (Metabolon Inc.) with untargeted liquid chromatography mass spectrometry and a comprehensive reference library. Analysis of a second sample obtained one year later was conducted in a subset. Of 1629 detected metabolites, 1074 (66%) were detected in all cohorts while only 10% were unique to one cohort, most of which were xenobiotics or uncharacterized. The major classes were lipids (28%), xenobiotics (22%), amino acids (14%), and uncharacterized (19%). The most abundant plasma metabolome components were the major dietary fatty acids and amino acids, glucose, lactate and creatinine. Most metabolites displayed a log-normal distribution. Temporal variability was generally similar to clinical chemistry analytes but more pronounced for xenobiotics. Extensive metabolite-metabolite correlations were observed but mainly restricted to within each class. Metabolites were broadly associated with clinical factors, particularly body mass index, sex and renal function. Collectively, our findings inform the conduct and interpretation of metabolite association and precision medicine studies.
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| 6. |
- Gjesdal, Grunde, et al.
(författare)
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Validation of cause of death classification after heart transplantation and cause-specific life expectancy compared to the general population
- 2022
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Ingår i: Clinical Transplantation. - : Wiley. - 0902-0063 .- 1399-0012. ; 36:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Post heart-transplant survival has increased, but information is lacking on specific causes of death and life expectancy. We aimed to assess cause-specific loss of life-years compared to the general population, evaluate classification for cause of death after heart transplantation, and assess validity of cause of death data from the International Society of Heart and Lung Transplant (ISHLT) registry. Methods: In this single center study, we included 239 heart recipients transplanted between 1988 and 2019 in Lund, Sweden (n = 239, 50% of the transplanted population where the cause of death was available). Two cardiologists retrospectively assigned causes of death according to a published classification (CLASS) in the 91 recipients who died during follow-up. Life expectancy was compared to data from the general population. Results: Compared to the average Swedish population, life expectancy for heart transplant recipients was 20 years shorter (IQR 12.9–27.2). The largest number of life-years lost were for deaths due to acute (49 years) and chronic rejection (27 years). Primary graft dysfunction (24 years) accounted for 24% of deaths, followed by malignancy (20 years) and infection (17 years), each accounting for ∼20% of deaths. Use of CLASS revealed moderate inter-rater agreement (56%) and moderate agreement with the ISHLT registry (62%). Conclusions: Survival after heart transplantation was 20 years lower than in the general population. In the young, more life-years were lost due to acute graft rejection, whereas chronic graft rejection and primary graft failure were more important causes of death in older patients. Agreement was moderate between CLASS and the ISHLT registry classifications.
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| 7. |
- Hägglund, Gunnar, et al.
(författare)
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Back pain is more frequent in girls and in children with scoliosis in the context of cerebral palsy
- 2019
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Ingår i: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253. ; 108:12, s. 2229-2234
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To investigate the prevalence of general and back pain in children with cerebral palsy and the relationships between scoliosis and back pain. Methods: Cross-sectional register study based on data from the Swedish Cerebral Palsy Follow-Up Programme. Descriptive analyses and logistic regression to regress age, sex, gross motor function, windswept, hip extension and source of report on the presence of pain. Results: The study included 3783 children (58% boys) 1-18 (mean 10.0) years of age. General pain was reported in 1538 (44% girls, 38% boys) and back pain in 226 (7% girls, 5% boys) children. The proportion of back pain increased from <4% prior to age 12 years to >12% from 16 years of age. Back pain increased from 4% in children without scoliosis to 16% in children with severe scoliosis. Moderate/severe back pain increased from 2% in children without scoliosis to 10% in children with severe scoliosis. Increased odds of reporting back pain were found for age, girls, low gross motor function and children with scoliosis. Conclusion: The proportion of children with general pain increased with age and was more frequent in girls. Age, female sex, low gross motor function and scoliosis were significant predictors of back pain.
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| 8. |
- Hägglund, Gunnar, et al.
(författare)
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Incidence of scoliosis in cerebral palsy : A population-based study of 962 young individuals
- 2018
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 89:4, s. 443-447
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose - Surveillance of scoliosis in individuals with cerebral palsy (CP) is important for ensuring timely diagnosis and identification of curve progression. We analyzed the incidence of scoliosis in relation to age, sex, and gross motor function in a population-based cohort of individuals with CP.Patients and methods - This was a prospective register study of all 1,025 individuals born 1990-2012 in southern Sweden (1.4 million inhabitants) in the Swedish surveillance program for CP, which included >95% of the total population of people with CP in the area. Annual clinical examinations and radiographic measurement of the Cobb angle of those with a moderate or severe scoliosis were registered. We determined the incidence of scoliosis related to age, sex, and the Gross Motor Function Classification System (GMFCS) level.Results - The inclusion criteria were fulfilled by 962 individuals. The number of people (140/962) with scoliosis increased up to 20-25 years of age. The incidence of scoliosis was related to age and GMFCS level. In individuals at the lowest level of gross motor function (GMFCS V) scoliosis was seen in 10/131 before 5 years of age and at the age of 20 years 75% of these individuals had a Cobb angle >= 40 degrees. No one in the highest level of motor function (GMFCS I) developed a Cobb angle > 40 degreesInterpretation - Surveillance programs for scoliosis in CP should be based on age and GMFCS level and should be initiated at a young age and continued into adulthood.
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| 9. |
- Hägglund, Gunnar, et al.
(författare)
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Self-versus Proxy-Reported Pain in Children with Cerebral Palsy : A Population-Based Registry Study of 3783 Children
- 2020
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Ingår i: Journal of Primary Care and Community Health. - : SAGE Publications. - 2150-1319 .- 2150-1327. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess how the prevalence of pain in a population-based sample of children and adolescents with cerebral palsy (CP) differ based on self- or proxy reporting. Methods: This cross-sectional registry study included 3783 children (58% boys), 1 to 18 years old, enrolled in the Swedish follow-up program for CP. Logistic regression was used to regress source of reporting (self or proxy) on the presence of general pain adjusted for age, sex, Gross Motor Function Classification System (GMFCS), and Communication Function Classification System (CFCS) levels, including marginal effects between source of reporting and adjusted covariates. Results: The pain item was self-reported in 45%, proxy-reported in 51%, and information was missing in 3%. Pain was reported in 44% of those who self-reported and in 41% of those who proxy-reported (P =.04). The logistic regression showed that the average marginal effects of proxy versus self-reported pain were lower among children at GMFCS level IV (−0.14, 95% CI −0.17 to −0.03) and CFCS level I (−0.09, CI −0.16 to −0.01) and higher at CFCS level III (0.11, CI 0.00-0.22). There were no statistically significant differences in average marginal effects related to age, sex, or the other GMFCS and CFCS levels between proxy and self-reporting. Conclusions: Pain was more often reported by those who self-reported. However, after adjusting for age, sex, CFCS level, and GMFCS level, the proportion of reported pain was almost equal between self and proxy-reporting. Assuming that the self- and proxy-reported groups were not significantly different on relevant factors not controlled for the results indicate that presence of pain is equally reported by children and parents.
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| 10. |
- Ibounig, Thomas, et al.
(författare)
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Concordance of shoulder symptoms and imaging findings: a protocol for the Finnish Imaging of Shoulder (FIMAGE) study
- 2023
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Ingår i: BMJ open. - 2044-6055. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Shoulder pain is a substantial medical and socioeconomic problem in most societies, affecting the ability to work or carry out leisure time activities as well as subsequently influencing physical and psychological well-being. According to a nationwide survey in Finland, 27% of the population reported shoulder pain within the last 30 days. In clinical practice, imaging findings of structural abnormalities are typically thought to explain symptoms, even though such findings are also prevalent in asymptomatic individuals, particularly with increasing age. Overall, there is a paucity of high-quality evidence on the prevalence, clinical relevance and prognosis of 'abnormal' imaging findings of the shoulder.The aim of the Finnish Imaging of Shoulder (FIMAGE) study is fourfold: to assess (1) the prevalence of shoulder symptoms and the most common anatomical variants and imaging abnormalities of the shoulder; (2) the concordance between shoulder symptoms, function and imaging abnormalities; (3) the most important determinants of symptoms, function and imaging abnormalities; and (4) the course of shoulder complaints over 5 years. METHODS: The FIMAGE target population of 600 participants, aged 40-75 years, will be randomly selected from a nationally representative general population sample of 9922 individuals originally recruited for the Finnish Health 2000 Survey. On giving informed consent, the participants will be invited to a clinical visit that includes assessment of general health, shoulder symptoms, bilateral shoulder examination and imaging of both shoulders with plain radiography and MRI. ETHICS AND DISSEMINATION: The study has been approved by the Institutional Review Board of the Helsinki and Uusimaa Hospital District. The findings will be published according to the Strengthening the Reporting of Observational Studies in Epidemiology criteria.
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