| 61. |
- Arvanitis, Panagiotis, et al.
(författare)
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Recent-onset atrial fibrillation : a study exploring the elements of Virchow's triad after cardioversion
- 2022
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Ingår i: Journal of Interventional Cardiac Electrophysiology. - : Springer Science and Business Media LLC. - 1383-875X .- 1572-8595. ; 64:1, s. 49-58
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Tidskriftsartikel (refereegranskat)abstract
- PurposeAtrial fibrillation (AF) imposes an inherent risk for stroke and silent cerebral emboli, partly related to left atrial (LA) remodeling and activation of inflammatory and coagulation systems. The aim was to explore the effects of cardioversion (CV) and short-lasting AF on left atrial hemodynamics, inflammatory, coagulative and cardiac biomarkers, and the association between LA functional recovery and the presence of a prior history of AF.MethodsPatients referred for CV within 48 h after AF onset were prospectively included. Echocardiography and blood sampling were performed immediately prior, 1–3 h after, and at 7–10 days after CV. The presence of chronic white matter hyperintensities (WMH) on magnetic resonance imaging was related to biomarker levels.ResultsForty-three patients (84% males), aged 55±9.6 years, with median CHA2DS2-VASc score 1 (IQR 0–1) were included. The LA emptying fraction (LAEF), LA peak longitudinal strain during reservoir, conduit, and contractile phases improved significantly after CV. Only LAEF normalized within 10 days. Interleukin-6, high-sensitivity cardiac-troponin-T (hs-cTNT), N-terminal-pro-brain-natriuretic peptide, prothrombin-fragment 1+2 (PTf1+2), and fibrinogen decreased significantly after CV. There was a trend towards higher C-reactive protein, hs-cTNT, and PTf1+2 levels in patients with WMH (n=21) compared to those without (n=22). At 7–10 days, the LAEF was significantly lower in patients with a prior history of AF versus those without.ConclusionAlthough LA stunning resolved within 10 days, LAEF remained significantly lower in patients with a prior history of AF versus those without. Inflammatory and coagulative biomarkers were higher before CV, but subsided after 7–10 days, which altogether might suggest an enhanced thrombogenicity, even in these low-risk patients.
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| 62. |
- Arvanitis, Panagiotis, et al.
(författare)
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Timing and degree of left atrial stunning and reverse functional remodeling following electrical cardioversion in patients with recent onset atrial fibrillation
- 2020
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Ingår i: European Heart Journal, Supplement. - : Oxford University Press (OUP). - 1520-765X .- 1554-2815 .- 0195-668X .- 1522-9645. ; 41:Supplement_2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundAtrial fibrillation (AF) results in left atrial electrical, structural and functional remodeling. Restoration of sinus rhythm hallmarks the beginning of reverse remodeling, the extent of which may depend on the type of AF.PurposeThe aim of the study was to assess resumption of left atrial function after electric cardioversion in patients with recent onset AF and to explore the association between reverse remodeling and the type of atrial fibrillation.MethodsPatients with AF duration <48 hours were prospectively included. Trans-thoracic echocardiography was performed prior, immediately after (2–4 hours) and 7–10 days following CV. Left atrial volume index (LAVI), left atrial global longitudinal strain during reservoir (LAGLS-res), conduit (LAGLS-cond) and contractile (LAGLS-contr) phases, left atrial ejection fraction (LAEF) and left ventricular ejection fraction (LVEF) were measured.ResultsForty-three patients (84% males) aged 55±9.6 years, (mean±SD), with median CHA2DS2-VASc score 1 (interquartile range 0–1) were included. Repeated measure analysis of variance revealed a statistically significant overall change for LAGLS-res F(2,78)=55.4, p<0,001, LAGLS-cond F(2,78)=23.3, p<0,001, LAGLS-contr F(2,78)=39.7, p<0,001, LAEF F(2,80)=28.5, p<0.001 and LVEF F(2,80)=8.4, p<0.001. At 7–10 days, LAGLS-contr 12±4%, LAEF 53±9% and LVEF 60±6 (mean±SD) return within normal reference intervals. Notably left atrial recovery seems to precede left ventricular recovery. No statistical significant interaction with the type of atrial fibrillation could be shown.ConclusionLeft atrial functional reverse remodeling occurs within ten days after successful electric cardioversion of patients with recent onset atrial fibrillation.
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| 63. |
- Austin, Thomas R., et al.
(författare)
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A plasma protein-based risk score to predict hip fractures
- 2024
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Ingår i: NATURE AGING. - 2662-8465. ; 4, s. 1064-1075
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Tidskriftsartikel (refereegranskat)abstract
- As there are effective treatments to reduce hip fractures, identification of patients at high risk of hip fracture is important to inform efficient intervention strategies. To obtain a new tool for hip fracture prediction, we developed a protein-based risk score in the Cardiovascular Health Study using an aptamer-based proteomic platform. The proteomic risk score predicted incident hip fractures and improved hip fracture discrimination in two Tr & oslash;ndelag Health Study validation cohorts using the same aptamer-based platform. When transferred to an antibody-based proteomic platform in a UK Biobank validation cohort, the proteomic risk score was strongly associated with hip fractures (hazard ratio per s.d. increase, 1.64; 95% confidence interval 1.53-1.77). The proteomic risk score, but not available polygenic risk scores for fractures or bone mineral density, improved the C-index beyond the fracture risk assessment tool (FRAX), which integrates information from clinical risk factors (C-index, FRAX 0.735 versus FRAX + proteomic risk score 0.776). The developed proteomic risk score constitutes a new tool for stratifying patients according to hip fracture risk; however, its improvement in hip fracture discrimination is modest and its clinical utility beyond FRAX with information on femoral neck bone mineral density remains to be determined. The authors developed a proteomic risk score that improved the prediction of hip fractures in three validation cohorts analyzed by two different proteomic platforms. This risk score constitutes a new tool to stratify patients by hip fracture risk.
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| 64. |
- Axelsson, Kristian F, 1973, et al.
(författare)
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Analysis of Comorbidities, Clinical Outcomes, and Parathyroidectomy in Adults With Primary Hyperparathyroidism
- 2022
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Ingår i: Jama Network Open. - : American Medical Association (AMA). - 2574-3805. ; 5:6
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Patients with primary hyperparathyroidism (pHPT) appear to have an increased risk of fractures and other comorbidities, such as cardiovascular disease, although results from previous studies have been inconsistent. Evidence of the association of parathyroidectomy (PTX) with these outcomes is also limited because of the lack of large well-controlled trials. OBJECTIVE To investigate whether untreated pHPT was associated with an increased risk of incident fractures and cardiovascular events (CVEs) and whether PTX was associated with a reduced risk of these outcomes. DESIGN, SETTING, AND PARTICIPANTS This cohort study included all patients who were diagnosed with pHPT at hospitals in Sweden between July 1, 2006, and December 31, 2017. Each patient was matched with 10 control individuals from the general population by sex, birth year, and county of residence. The patients were followed up until December 31, 2017. Data analyses were performed from October 2021 to April 2022. MAIN OUTCOMES AND MEASURES The primary outcomes were fractures, CVEs, and death. Cumulative incidence of events was estimated using the 1-minus Kaplan-Meier estimator of corresponding survival function. Cox proportional hazards regression models were used to calculate hazard ratios (HRs). RESULTS A total of 16 374 patients with pHPT were identified (mean [SD] age, 67.5 [12.9] years; 12 806 women [78.2%]), with 163 740 control individuals. The follow-up time was 42 310 person-years for the pH PT group and 803 522 person-years for the control group. Compared with the control group, the pH PT group had a higher risk of any fracture (unadjusted HR, 1.39; 95% CI, 1.31-1.48), hip fracture (unadjusted HR, 1.51; 95% CI, 1.35-1.70), CVEs (unadjusted HR, 1.45; 95% CI, 1.34-1.57), and death (unadjusted HR, 1.72; 95% CI, 1.65-1.80). In a time-dependent Poisson regression model, PTX was associated with a reduced risk of any fracture (HR, 0.83; 95% CI, 0.75-0.93), hip fracture (HR, 0.78; 95% CI, 0.61-0.98), CVEs (HR, 0.84; 95% CI, 0.73-0.97), and death (HR, 0.59; 95% CI, 0.53-0.65). CONCLUSIONS AND RELEVANCE Results of this study suggest that pHPT is associated with increased risk of fractures, CVEs, and death, highlighting the importance of identifying patients with this condition to prevent serious unfavorable outcomes. The reduced risk of these outcomes associated with PTX suggests a clinical benefit of surgery.
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| 65. |
- Axelsson, Kristian F., et al.
(författare)
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Association Between Recurrent Fracture Risk and Implementation of Fracture Liaison Services in Four Swedish Hospitals: A Cohort Study
- 2020
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 35:7, s. 1216-1223
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Tidskriftsartikel (refereegranskat)abstract
- © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research Structured secondary preventions programs, called fracture liaison services (FLSs), increase the rate of evaluation with bone densitometry and use of osteoporosis medication after fracture. However, the evidence regarding the effect on the risk of recurrent fracture is insufficient. The aim of this study was to investigate if implementation of FLS was associated with reduced risk of recurrent fractures. In this retrospective cohort study, electronic health records during 2012 to 2017 were used to identify a total of 21,083 patients from four hospitals in Western Sweden, two with FLS (n = 15,449) and two without (n = 5634). All patients aged 50 years or older (mean age 73.9 [SD 12.4] years, 76% women) with a major osteoporotic index fracture (hip, clinical spine, humerus, radius, and pelvis) were included. The primary outcome was recurrent major osteoporotic fracture. All patients with an index fracture during the FLS period (n = 13,946) were compared with all patients in the period before FLS implementation (n = 7137) in an intention-to-treat analysis. Time periods corresponding to the FLS hospitals were used for the non-FLS hospitals. In the hospitals with FLSs, there were 1247 recurrent fractures during a median follow-up time of 2.2 years (range 0–6 years). In an unadjusted Cox model, the risk of recurrent fracture was 18% lower in the FLS period compared with the control period (hazard ratio = 0.82, 95% confidence interval [CI] 0.73–0.92, p = 0.001), corresponding to a 3-year number needed to screen of 61, and did not change after adjustment for clinical risk factors. In the hospitals without FLSs, no change in recurrent fracture rate was observed. Treatment decisions were made according to the Swedish treatment guidelines. In conclusion, implementation of FLS was associated with a reduced risk of recurrent fracture, indicating that FLSs should be included routinely at hospitals treating fracture patients. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
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| 66. |
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| 67. |
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| 68. |
- Basu, Samar, et al.
(författare)
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Association between oxidative stress and bone mineral density
- 2001
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 288:1, s. 275-9
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Tidskriftsartikel (refereegranskat)abstract
- Free radicals have been shown to be involved in bone resorption in vitro and in rodents. We studied the effect of oxidative stress on bone mineral density (BMD) in 48 women and 53 men from a population-based study. The levels of 8-iso-PGF(2alpha) (a major F(2)-isoprostane and a biomarker of oxidative stress) and a control, 15-keto-dihydro-PGF(2alpha) (a biomarker of inflammatory response), were measured in urinary samples and their association with BMD and quantitative ultrasound (QUS) measurements were examined. In multivariate linear regression analyses, 8-iso-PGF(2alpha) levels were negatively associated with both BMD and QUS. In contrast, no association was found for 15-keto-dihydro-PGF(2alpha). Our findings establish a biochemical link between increased oxidative stress and reduced bone density and provide a rational for further studies investigating the role of pro- and antioxidants in osteoporosis. Copyright 2001 Academic Press.
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| 69. |
- Belfrage, Anna Karin, 1977-, et al.
(författare)
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Pan-NS3 protease inhibitors of hepatitis C virus based on an R3-elongated pyrazinone scaffold
- 2018
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier. - 0223-5234 .- 1768-3254. ; 148, s. 453-464
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Tidskriftsartikel (refereegranskat)abstract
- Herein, we present the design and synthesis of 2(1H)-pyrazinone based HCV NS3 protease inhibitors and show that elongated R-3 urea substituents were associated with increased inhibitory potencies over several NS3 protein variants. The inhibitors are believed to rely on beta-sheet mimicking hydrogen bonds which are similar over different genotypes and current drug resistant variants and correspond to the beta-sheet interactions of the natural peptide substrate. Inhibitor 36, for example, with a urea substituent including a cyclic imide showed balanced nanomolar inhibitory potencies against genotype la, both wild-type (K-i=30 nM) and R155K (K-i=2 nM), and genotype 3a (K-i=5 nM).
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| 70. |
- Bengtsson-Palme, Johan, 1985, et al.
(författare)
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The human gut microbiome as a transporter of antibiotic resistance genes between continents
- 2015
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Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 59:10, s. 6551-6560
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies of antibiotic resistance dissemination by travel have, by targeting only a select number of cultivable bacterial species, omitted most of the human microbiome. Here, we used explorative shotgun metagenomic sequencing to address the abundance of >300 antibiotic resistance genes in fecal specimens from 35 Swedish students taken before and after exchange programs on the Indian peninsula or in Central Africa. All specimens were additionally cultured for extended-spectrum beta-lactamase (ESBL)-producing enterobacteria, and the isolates obtained were genome sequenced. The overall taxonomic diversity and composition of the gut microbiome remained stable before and after travel, but there was an increasing abundance of Proteobacteria in 25/35 students. The relative abundance of antibiotic resistance genes increased, most prominently for genes encoding resistance to sulfonamide (2.6-fold increase), trimethoprim (7.7-fold), and beta-lactams (2.6-fold). Importantly, the increase observed occurred without any antibiotic intake. Of 18 students visiting the Indian peninsula, 12 acquired ESBL-producing Escherichia coli, while none returning from Africa were positive. Despite deep sequencing efforts, the sensitivity of metagenomics was not sufficient to detect acquisition of the low-abundant genes responsible for the observed ESBL phenotype. In conclusion, metagenomic sequencing of the intestinal microbiome of Swedish students returning from exchange programs in Central Africa or the Indian peninsula showed increased abundance of genes encoding resistance to widely used antibiotics.
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