| 1. |
- Allesøe, Rosa Lundbye, et al.
(författare)
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Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
- 2023
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 41:3, s. 399-408
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Tidskriftsartikel (refereegranskat)abstract
- The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug–omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug–drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.
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| 2. |
- Alkner, Sara, et al.
(författare)
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Quality assessment of radiotherapy in the prospective randomized SENOMAC trial
- 2024
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Ingår i: Radiotherapy and Oncology. - 0167-8140 .- 1879-0887. ; 197
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Recommendations for regional radiotherapy (RT) of sentinel lymph node (SLN)-positive breast cancer are debated. We here report a RT quality assessment of the SENOMAC trial.Materials and Methods: The SENOMAC trial randomized clinically node-negative breast cancer patients with 1–2 SLN macrometastases to completion axillary lymph node dissection (cALND) or SLN biopsy only between 2015–2021. Adjuvant RT followed national guidelines. RT plans for patients included in Sweden and Denmark until June 2019 were collected (N = 1176) and compared to case report forms (CRF). Dose to level I (N = 270) and the humeral head (N = 321) was analyzed in detail.Results: CRF-data and RT plans agreed in 99.3 % (breast/chest wall) and in 96.6 % of patients (regional RT). Congruence for whether level I was an intended RT target was lower (78 %). In accordance with Danish national guidelines, level I was more often an intended target in the SLN biopsy only arm (N = 334/611, 55 %,) than in the cALND arm (N = 174/565, 31 %,). When an intended target, level I received prescribed dose to 100 % (IQR 98–100 %) of the volume. However, even when not an intended target, full dose was delivered to > 80 % of level I (IQR 75–90 %). The intentional inclusion of level I in the target volume more than doubled the dose received by ≥ 50 % of the humeral head.Conclusion: Congruence between CRF data and RT plans was excellent. Level I received a high dose coverage even when not intentionally included in the target. Including level I in target significantly increased dose to the humeral head.
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| 3. |
- Alkner, Sara, et al.
(författare)
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Quality assessment of radiotherapy in the prospective randomized SENOMAC trial
- 2024
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Ingår i: Radiotherapy and Oncology. - : Elsevier. - 0167-8140 .- 1879-0887. ; 197
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Recommendations for regional radiotherapy (RT) of sentinel lymph node (SLN)-positive breast cancer are debated. We here report a RT quality assessment of the SENOMAC trial. Materials and Methods: The SENOMAC trial randomized clinically node-negative breast cancer patients with 1-2 SLN macrometastases to completion axillary lymph node dissection (cALND) or SLN biopsy only between 2015-2021. Adjuvant RT followed national guidelines. RT plans for patients included in Sweden and Denmark until June 2019 were collected (N = 1176) and compared to case report forms (CRF). Dose to level I (N = 270) and the humeral head (N = 321) was analyzed in detail.
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| 4. |
- Hojsgaard Jorgensen, Troels, et al.
(författare)
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Eight-year outcomes for patients with aortic valve stenosis at low surgical risk randomized to transcatheter vs. surgical aortic valve replacement.
- 2021
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 42:30, s. 2912-2919
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Tidskriftsartikel (refereegranskat)abstract
- The aims of the study were to compare clinical outcomes and valve durability after 8 years of follow-up in patients with symptomatic severe aortic valve stenosis at low surgical risk treated with either transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR).In the NOTION trial, patients with symptomatic severe aortic valve stenosis were randomized to TAVI or SAVR. Clinical status, echocardiography, structural valve deterioration, and failure were assessed using standardized definitions. In total, 280 patients were randomized to TAVI (n=145) or SAVR (n=135). Baseline characteristics were similar, including mean age of 79.1±4.8 years and a mean STS score of 3.0±1.7%. At 8-year follow-up, the estimated risk of the composite outcome of all-cause mortality, stroke, or myocardial infarction was 54.5% after TAVI and 54.8% after SAVR (P=0.94). The estimated risks for all-cause mortality (51.8% vs. 52.6%; P=0.90), stroke (8.3% vs. 9.1%; P=0.90), or myocardial infarction (6.2% vs. 3.8%; P=0.33) were similar after TAVI and SAVR. The risk of structural valve deterioration was lower after TAVI than after SAVR (13.9% vs. 28.3%; P=0.0017), whereas the risk of bioprosthetic valve failure was similar (8.7% vs. 10.5%; P=0.61).In patients with severe aortic valve stenosis at low surgical risk randomized to TAVI or SAVR, there were no significant differences in the risk for all-cause mortality, stroke, or myocardial infarction, as well as the risk of bioprosthetic valve failure after 8 years of follow-up.URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01057173.
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| 5. |
- Ihlberg, Leo, et al.
(författare)
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Early clinical outcome of aortic transcatheter valve-in-valve implantation in the Nordic countries
- 2013
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Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : Elsevier. - 0022-5223 .- 1097-685X. ; 146:5, s. 1047-1054
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Transcatheter valve-in-valve implantation has emerged as an option, in addition to reoperative surgical aortic valve replacement, to treat failed biologic heart valve substitutes. However, the clinical experience with this approach is still limited. We report the comprehensive experience of transcatheter valve-in-valve implantation in the Nordic countries from May 2008 to January 2012. less thanbrgreater than less thanbrgreater thanMethods: A total of 45 transcatheter aortic valve-in-valve implantations were performed during the study period in 11 centers. The mean age of the patients was 80.6 years (range, 61-91), 26 were male and 19 were female, and the mean EuroSCORE, EuroSCORE II, and Society of Thoracic Surgeons score was 35.4, 16.3, and 14.6, respectively. The type of failure was stenosis and combined in 58% (mean and peak aortic valve gradient, 77 and 45 mm Hg, respectively) and regurgitation in 42% of cases. The SAPIEN/XT (Edwards LifeSciences, Irvine, Calif) and CoreValve (Medtronic Inc, Minneapolis, Minn) system was used in 33 and 12 cases, respectively. The access route was transapical in 25, transfemoral in 17, transaortic in 2, and subclavian in 1 case. The mean follow-up was 14.4 months. The periprocedural and postoperative outcomes were assessed using the Valve Academic Research Consortium criteria. less thanbrgreater than less thanbrgreater thanResults: No intraprocedural mortality occurred. The technical success rate was 95.6% (1 second valve implantation, 1 conversion to open surgery). The all-cause 30-day mortality was 4.4% (1 cardiac-related and 1 aspiration pneumonia). The major complications within 30 days included stroke in 2.2%, periprocedural myocardial infarction in 4.4%, and major vascular complication in 2.2% of patients. At 1 month, all but 1 patient had either no or mild paravalvular leakage, with a mean and peak valve gradient of 17 mm Hg (range, 4-38) and 30 mm Hg (range, 7-68), respectively. The mean gradient was greater than 20 mm Hg in 17% of patients and remained unchanged at 12 months. The 1-year survival was 88.1%. less thanbrgreater than less thanbrgreater thanConclusions: Transcatheter valve-in-valve implantation is widely performed, albeit in small numbers, in most centers in the Nordic countries. The short-termresults were excellent in this high-risk patient population, demonstrating a low incidence of device-or procedure-related complications. However, a considerable number of patients were left with suboptimal systolic valve performance with unknown long-term effects, warranting close surveillance after transcatheter valve-in-valve implantation.
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| 6. |
- Jönsson, Henrik, et al.
(författare)
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Sulphur abundances in halo giants from the [S I] line at 1082 nm and the [S I] triplet around 1045 nm
- 2011
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 530, s. A144-
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Tidskriftsartikel (refereegranskat)abstract
- Context. It is still debated whether or not the Galactic chemical evolution of sulphur in the halo follows the flat trend with [Fe/H] that is ascribed to the result of explosive nucleosynthesis in type II SNe. It has been suggested that the disagreement between different investigations of sulphur abundances in halo stars might be owing to problems with the diagnostics used, that a new production source of sulphur might be needed in the early Universe, like hypernovae, or that the deposition of supernova ejecta into the interstellar medium is time-delayed. Aims. The aim of this study is to try to clarify this situation by measuring the sulphur abundance in a sample of halo giants using two diagnostics: the S I triplet around 1045 nm and the [S I] line at 1082 nm. The latter of the two is not believed to be sensitive to non-LTE effects. We can thereby minimize the uncertainties in the diagnostic used and estimate the usefulness of the triplet for the sulphur determination in halo K giants. We will also be able to compare our sulphur abundance differences from the two diagnostics with the expected non-LTE effects in the 1045 nm triplet previously calculated by others. Methods. High-resolution near-infrared spectra of ten K giants were recorded using the spectrometer CRIRES mounted at VLT. Two standard settings were used, one covering the S I triplet and one covering the [S I] line. The sulphur abundances were individually determined with equivalent widths and synthetic spectra for the two diagnostics using tailored 1D model atmospheres and relying on non-LTE corrections from the litterature. Effects of convective inhomogeneities in the stellar atmospheres are investigated. Results. The sulphur abundances derived from both the [S I] line and the non-LTE corrected 1045 nm triplet favor a flat trend for the evolution of sulphur. In contrast to some previous studies, we saw no "high" values of [S/Fe] in our sample. Conclusions. We corroborate the flat trend in the [S/Fe] vs. [Fe/H] plot for halo stars found in some previous studies but do not find a scatter or a rise in [S/Fe] as obtained in other works. We find the sulphur abundances deduced from the non-LTE corrected triplet to be somewhat lower than the abundances from the [S I] line, possibly indicating too large non-LTE corrections. Considering 3D modeling, however, they might instead be too small. Moreover, we show that the [S I] line can be used as a sulphur diagnostic down to [Fe/H] similar to - 2.3 in giants.
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| 7. |
- Thyregod, Hans Gustav Hørsted, et al.
(författare)
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Transcatheter or surgical aortic valve implantation: 10-year outcomes of the NOTION trial.
- 2024
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Ingår i: European heart journal. - 1522-9645.
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Tidskriftsartikel (refereegranskat)abstract
- Transcatheter aortic valve implantation (TAVI) has become a viable treatment option for patients with severe aortic valve stenosis across a broad range of surgical risk. The Nordic Aortic Valve Intervention (NOTION) trial was the first to randomize patients at lower surgical risk to TAVI or surgical aortic valve replacement (SAVR). The aim of the present study was to report clinical and bioprosthesis outcomes after 10 years.The NOTION trial randomized 280 patients to TAVI with the self-expanding CoreValve (Medtronic Inc.) bioprosthesis (n = 145) or SAVR with a bioprosthesis (n = 135). The primary composite outcome was the risk of all-cause mortality, stroke, or myocardial infarction. Bioprosthetic valve dysfunction (BVD) was classified as structural valve deterioration (SVD), non-structural valve dysfunction (NSVD), clinical valve thrombosis, or endocarditis according to Valve Academic Research Consortium-3 criteria. Severe SVD was defined as (i) a transprosthetic gradient of 30mmHg or more and an increase in transprosthetic gradient of 20mmHg or more or (ii) severe new intraprosthetic regurgitation. Bioprosthetic valve failure (BVF) was defined as the composite rate of death from a valve-related cause or an unexplained death following the diagnosis of BVD, aortic valve re-intervention, or severe SVD.Baseline characteristics were similar between TAVI and SAVR: age 79.2 ± 4.9 years and 79.0 ± 4.7 years (P = .7), male 52.6% and 53.8% (P = .8), and Society of Thoracic Surgeons score < 4% of 83.4% and 80.0% (P = .5), respectively. After 10 years, the risk of the composite outcome all-cause mortality, stroke, or myocardial infarction was 65.5% after TAVI and 65.5% after SAVR [hazard ratio (HR) 1.0; 95% confidence interval (CI) 0.7-1.3; P = .9], with no difference for each individual outcome. Severe SVD had occurred in 1.5% and 10.0% (HR 0.2; 95% CI 0.04-0.7; P = .02) after TAVI and SAVR, respectively. The cumulative incidence for severe NSVD was 20.5% and 43.0% (P < .001) and for endocarditis 7.2% and 7.4% (P = 1.0) after TAVI and SAVR, respectively. No patients had clinical valve thrombosis. Bioprosthetic valve failure occurred in 9.7% of TAVI and 13.8% of SAVR patients (HR 0.7; 95% CI 0.4-1.5; P = .4).In patients with severe AS and lower surgical risk randomized to TAVI or SAVR, the risk of major clinical outcomes was not different 10 years after treatment. The risk of severe bioprosthesis SVD was lower after TAVR compared with SAVR, while the risk of BVF was similar.
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