| 1. |
- Gunst, Jesper D., et al.
(författare)
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Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial
- 2021
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Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 35
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Tidskriftsartikel (refereegranskat)abstract
- Background: The trans-membrane protease serine 2 (TMPRSS2) is essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry and infection. Efficacy and safety of TMPRSS2 inhibitors in patients with coronavirus disease 2019 (Covid-19) have not been evaluated in randomized trials.Methods: We conducted an investigator-initiated, double-blind, randomized, placebo-controlled multicenter trial in patients hospitalized with confirmed SARS-CoV-2 infection from April 4, to December 31, 2020. Within 48 h of admission, participants were randomly assigned in a 2:1 ratio to receive the TMPRSS2 inhibitor camostat mesilate 200 mg three times daily for 5 days or placebo. The primary outcome was time to discharge or clinical improvement measured as ≥2 points improvement on a 7-point ordinal scale. Other outcomes included 30-day mortality, safety and change in oropharyngeal viral load. ClinicalTrials.gov Identifier: NCT04321096. EudraCT Number: 2020-001,200-42.Findings: 137 patients were assigned to receive camostat mesilate and 68 to placebo. Median time to clinical improvement was 5 days (interquartile range [IQR], 3 to 7) in the camostat group and 5 days (IQR, 2 to 10) in the placebo group (P = 0·31). The hazard ratio for 30-day mortality in the camostat compared with the placebo group was 0·82 (95% confidence interval [CI], 0·24 to 2·79; P = 0·75). The frequency of adverse events was similar in the two groups. Median change in viral load from baseline to day 5 in the camostat group was -0·22 log10 copies/mL (p <0·05) and -0·82 log10 in the placebo group (P <0·05).Interpretation: Under this protocol, camostat mesilate treatment was not associated with increased adverse events during hospitalization for Covid-19 and did not affect time to clinical improvement, progression to ICU admission or mortality.
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| 2. |
- Broesby-Olsen, Sigurd, et al.
(författare)
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Multidisciplinary Management of Mastocytosis : Nordic Expert Group Consensus
- 2016
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 96:5
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Tidskriftsartikel (refereegranskat)abstract
- Mastocytosis is a heterogeneous group of diseases defined by an increased number and accumulation of mast cells, and often also by signs and symptoms of mast cell activation. Disease subtypes range from indolent to rare aggressive forms. Mastocytosis affects people of all ages and has been considered rare; however, it is probably underdiagnosed with potential severe implications. Diagnosis can be challenging and symptoms may be complex and involve multiple organ-systems. In general it is advised that patients should be referred to centres with experience in the disease offering an individualized, multidisciplinary approach. We present here consensus recommendations from a Nordic expert group for the diagnosis and general management of patients with mastocytosis.
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| 3. |
- Erlström, Mikael, et al.
(författare)
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Stratigraphy and geothermal assessment of Mesozoic sandstone reservoirs in the Öresund Basin - exemplified by well data and seismic profiles
- 2018
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Ingår i: Bulletin of the Geological Society of Denmark. - 0011-6297. ; 66, s. 123-149
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Tidskriftsartikel (refereegranskat)abstract
- The Øresund Basin in the transnational area between Sweden and Denmark forms a marginal part of the Danish Basin. The structural outline and stratigraphy of the Mesozoic succession is described, and a novel interpretation and description of the subsurface geology and geothermal potential in the North Sjælland Half-graben is presented. The subsurface bedrock in the basin includes several Mesozoic intervals with potential geothermal sandstone reservoirs. Parts of the succession fulfill specific geological requirements about distribution, composition and quality of the sandstones. A characterisation of these is presently of great interest in the attempt to identify geothermal reservoirs suitable for district heating purposes. The results presented in this paper include for the first time a comprehensive description of the stratigraphic intervals as well as the characteristics of the potential Mesozoic geothermal reservoirs in the Øresund region, including their distribution, composition and physical properties. This is illustrated by seismic cross-sections and well sections. In addition, results from analyses and evaluations of porosity, permeability, formation fluids and temperature are presented. Six potential geothermal reservoirs in the Mesozoic succession are described and assessed. Primary focus is placed on the characteristics of the reservoirs in the Lower Triassic and Rhaetian–Lower Jurassic succession. The study shows that the Mesozoic reservoir sandstones vary considerably with respect to porosity and permeability. Values range between 5–25% for the pre-Rhaetian Triassic sandstones, but are commonly > 25% for the Rhaetian–Lower Jurassic and Lower Cretaceous sandstones. The corresponding permeability rarely reaches above 500 mD for the pre-Rhaetian Triassic reservoirs, but often reach >1 Darcy for the Rhaetian–Lower Jurassic and the Lower Cretaceous sandstones. The interpreted formation temperatures for the reservoirs in the Øresund Basin are: 45–50°C at 1500 m, 60–70°C at 2000 m and 70–90°C at 2500 m depth . The combined results provide a geological framework for making site specific predictions regarding appraisal of viable geothermal projects for district heating purposes in the region as well as reducing the risk of unsuccessful wells
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| 4. |
- Fedorov, R V, et al.
(författare)
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Structure of ribosomal protein TL5 complexed with RNA provides new insights into the CTC family of stress proteins
- 2001
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Ingår i: Acta Crystallographica. Section D: Biological Crystallography. - 1399-0047. ; D57:7, s. 968-976
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Tidskriftsartikel (refereegranskat)abstract
- The crystal structure of Thermus thermophilus ribosomal protein TL5 in complex with a fragment of Escherichia coli 5S rRNA has been determined at 2.3 Å resolution. The protein consists of two domains. The structure of the N-terminal domain is close to the structure of E. coli ribosomal protein L25, but the C-terminal domain represents a new fold composed of seven -strands connected by long loops. TL5 binds to the RNA through its N-terminal domain, whereas the C-terminal domain is not included in this interaction. Cd2+ ions, the presence of which improved the crystal quality significantly, bind only to the protein component of the complex and stabilize the protein molecule itself and the interactions between the two molecules in the asymmetric unit of the crystal. The TL5 sequence reveals homology to the so-called general stress protein CTC. The hydrophobic cores which stabilize both TL5 domains are highly conserved in CTC proteins. Thus, all CTC proteins may fold with a topology close to that of TL5.
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| 5. |
- Holm, Niels R, et al.
(författare)
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OCT or Angiography Guidance for PCI in Complex Bifurcation Lesions.
- 2023
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Ingår i: The New England journal of medicine. - 1533-4406. ; 389:16, s. 1477-1487
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Tidskriftsartikel (refereegranskat)abstract
- Imaging-guided percutaneous coronary intervention (PCI) is associated with better clinical outcomes than angiography-guided PCI. Whether routine optical coherence tomography (OCT) guidance in PCI of lesions involving coronary-artery branch points (bifurcations) improves clinical outcomes as compared with angiographic guidance is uncertain.We conducted a multicenter, randomized, open-label trial at 38 centers in Europe. Patients with a clinical indication for PCI and a complex bifurcation lesion identified by means of coronary angiography were randomly assigned in a 1:1 ratio to OCT-guided PCI or angiography-guided PCI. The primary end point was a composite of major adverse cardiac events (MACE), defined as death from a cardiac cause, target-lesion myocardial infarction, or ischemia-driven target-lesion revascularization at a median follow-up of 2 years.We assigned 1201 patients to OCT-guided PCI (600 patients) or angiography-guided PCI (601 patients). A total of 111 patients (18.5%) in the OCT-guided PCI group and 116 (19.3%) in the angiography-guided PCI group had a bifurcation lesion involving the left main coronary artery. At 2 years, a primary end-point event had occurred in 59 patients (10.1%) in the OCT-guided PCI group and in 83 patients (14.1%) in the angiography-guided PCI group (hazard ratio, 0.70; 95% confidence interval, 0.50 to 0.98; P=0.035). Procedure-related complications occurred in 41 patients (6.8%) in the OCT-guided PCI group and 34 patients (5.7%) in the angiography-guided PCI group.Among patients with complex coronary-artery bifurcation lesions, OCT-guided PCI was associated with a lower incidence of MACE at 2 years than angiography-guided PCI. (Funded by Abbott Vascular and others; OCTOBER ClinicalTrials.gov number, NCT03171311.).
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| 6. |
- Johansson, Henrik J., et al.
(författare)
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Breast cancer quantitative proteome and proteogenomic landscape
- 2019
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- In the preceding decades, molecular characterization has revolutionized breast cancer (BC) research and therapeutic approaches. Presented herein, an unbiased analysis of breast tumor proteomes, inclusive of 9995 proteins quantified across all tumors, for the first time recapitulates BC subtypes. Additionally, poor-prognosis basal-like and luminal B tumors are further subdivided by immune component infiltration, suggesting the current classification is incomplete. Proteome-based networks distinguish functional protein modules for breast tumor groups, with co-expression of EGFR and MET marking ductal carcinoma in situ regions of normal-like tumors and lending to a more accurate classification of this poorly defined subtype. Genes included within prognostic mRNA panels have significantly higher than average mRNA-protein correlations, and gene copy number alterations are dampened at the protein-level; underscoring the value of proteome quantification for prognostication and phenotypic classification. Furthermore, protein products mapping to non-coding genomic regions are identified; highlighting a potential new class of tumor-specific immunotherapeutic targets.
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| 7. |
- Kristensen, Ole, et al.
(författare)
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Crystallization of a stringent response factor from Aquifex aeolicus.
- 2002
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Ingår i: Acta Crystallographica. Section D: Biological Crystallography. - 1399-0047. ; 58:Pt 7, s. 1198-1200
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Tidskriftsartikel (refereegranskat)abstract
- The crystallization of a key enzyme from Aquifex aeolicus with suggested bifunctional activity, acting as an exopolyphosphatase and a guanosine pentaphosphate phosphohydrolase, is reported. Native data were collected to below 2 A resolution from an orthorhombic crystal with unit-cell parameters a = 50.8, b = 70.3, c = 90.9 A. Methionine residues were introduced by mutation and deliberate oxidation of the protein allowed us to produce additional crystal forms with reproducible diffraction ability and increased phasing potential. This is the first report on the crystallization of a member of the Ppx/GppA phosphatase family.
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| 8. |
- Kristensen, Ole, et al.
(författare)
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Expression, refolding and crystallization of Aquifex aeolicus elongation factor P.
- 2002
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Ingår i: Acta Crystallographica. Section D: Biological Crystallography. - 1399-0047. ; D58:Pt 6 Nr 2, s. 1039-1041
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Tidskriftsartikel (refereegranskat)abstract
- Elongation factor P is a universally conserved protein stimulating peptidyltransferase activity during protein synthesis. The factor is sensitive to classical inhibitors of the ribosomal peptidyltransferase activity and is possibly involved in alignment of the substrate tRNAs in the catalytic centre of 70S ribosomes. Elongation factor P from the thermophilic Aquifex aeolicus was overexpressed as a soluble protein in Escherichia coli and crystallized. A fast generally applicable refolding protocol was developed to improve crystal quality and circumvent strong binding of oligonucleotides to the protein. Diffraction data collected to 2.7 A resolution present twinning.
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| 9. |
- Metcalfe, Daniel B., et al.
(författare)
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Ecological stoichiometry and nutrient partitioning in two insect herbivores responsible for large-scale forest disturbance in the Fennoscandian subarctic
- 2019
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Ingår i: Ecological Entomology. - : Wiley. - 0307-6946 .- 1365-2311. ; 44:1, s. 118-128
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Tidskriftsartikel (refereegranskat)abstract
- 1. Outbreaks of herbivorous insects can have large impacts on regional soil carbon (C) storage and nutrient cycling. In northernmost Europe, population outbreaks of several geometrid moth species regularly cause large-scale defoliation in subarctic birch forests. An improved understanding is required of how leaf C and nutrients are processed after ingestion by herbivores and what this means for the quantity and quality of different materials produced (frass, bodies). 2. In this study, larvae of two geometrid species responsible for major outbreaks (Epirrita autumnata and Operophtera brumata) were raised on exclusive diets of Betula pubescens var. czerepanovii (N. I. Orlova) Hämet Ahti and two other abundant understorey species (Betula nana, Vaccinium myrtillus). The quantities of C, nitrogen (N) and phosphorus (P) ingested and allocated to frass, bodies and (in the case of C) respired were recorded. 3. Overall, 23%, 70% and 48% of ingested C, N and P were allocated to bodies, respectively, rather than frass and (in the case of C) respiration. Operophtera brumata consistently maintained more constant body stoichiometric ratios of C, N and P than did E. autumnata, across the wide variation in physico-chemical properties of plant diet supplied. 4. These observed differences and similarities on C and nutrient processing may improve researchers' ability to predict the amount and stoichiometry of frass and bodies generated after geometrid outbreaks.
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| 10. |
- Nan, Jie, et al.
(författare)
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Bioinformatics and structural characterization of a hypothetical protein from Streptococcus mutans : implication of antibiotic resistance
- 2009
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:10, s. 7245-7245
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Tidskriftsartikel (refereegranskat)abstract
- As an oral bacterial pathogen, Streptococcus mutans has been known as the aetiologic agent of human dental caries. Among a total of 1960 identified proteins within the genome of this organism, there are about 500 without any known functions. One of these proteins, SMU.440, has very few homologs in the current protein databases and it does not fall into any protein functional families. Phylogenetic studies showed that SMU.440 is related to a particular ecological niche and conserved specifically in some oral pathogens, due to lateral gene transfer. The co-occurrence of a MarR protein within the same operon among these oral pathogens suggests that SMU.440 may be associated with antibiotic resistance. The structure determination of SMU.440 revealed that it shares the same fold and a similar pocket as polyketide cyclases, which indicated that it is very likely to bind some polyketide-like molecules. From the interlinking structural and bioinformatics studies, we have concluded that SMU.440 could be involved in polyketide-like antibiotic resistance, providing a better understanding of this hypothetical protein. Besides, the combination of multiple methods in this study can be used as a general approach for functional studies of a protein with unknown function.
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| 11. |
- Nan, Jie, et al.
(författare)
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Structure of a fatty-acid-binding protein from Bacillus subtilis determined by sulfur-SAD phasing using in-house chromium radiation
- 2009
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Ingår i: Acta Crystallographica. Section D: Biological Crystallography. - 1399-0047. ; 65:Pt 5, s. 8-440
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Tidskriftsartikel (refereegranskat)abstract
- Sulfur single-wavelength anomalous dispersion (S-SAD) and halide-soaking methods are increasingly being used for ab initio phasing. With the introduction of in-house Cr X-ray sources, these methods benefit from the enhanced anomalous scattering of S and halide atoms, respectively. Here, these methods were combined to determine the crystal structure of BsDegV, a DegV protein-family member from Bacillus subtilis. The protein was cocrystallized with bromide and low-redundancy data were collected to 2.5 A resolution using Cr Kalpha radiation. 17 heavy-atom sites (ten sulfurs and seven bromides) were located using standard methods. The anomalous scattering of some of the BsDegV S atoms and Br atoms was weak, thus neither sulfurs nor bromides could be used alone for structure determination using the collected data. When all 17 heavy-atom sites were used for SAD phasing, an easily interpretable electron-density map was obtained after density modification. The model of BsDegV was built automatically and a palmitate was found tightly bound in the active site. Sequence alignment and comparisons with other known DegV structures provided further insight into the specificity of fatty-acid selection and recognition within this protein family.
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| 12. |
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| 13. |
- Otzen, Daniel E, et al.
(författare)
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Designed protein tetramer zipped together with a hydrophobic Alzheimer homology: A structural clue to amyloid assembly
- 2000
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Ingår i: PNAS. - : Proceedings of the National Academy of Sciences. ; , s. 9907-12
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Tidskriftsartikel (refereegranskat)abstract
- Limited solubility and precipitation of amyloidogenic sequences such as the Alzheimer peptide (-AP) are major obstacles to a molecular understanding of protein fibrillation and deposition processes. Here we have circumvented the solubility problem by stepwise engineering a -AP homology into a soluble scaffold, the monomeric protein S6. The S6 construct with the highest -AP homology crystallizes as a tetramer that is linked by the -AP residues forming intermolecular antiparallel -sheets. This construct also shows increased coil aggregation during refolding, and a 14-mer peptide encompassing the engineered sequence forms fibrils. Mutational analysis shows that intermolecular association is linked to the overall hydrophobicity of the sticky sequence and implies the existence of "structural gatekeepers" in the wild-type protein, that is, charged side chains that prevent aggregation by interrupting contiguous stretches of hydrophobic residues in the primary sequence.
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| 14. |
- Otzen, Daniel E, et al.
(författare)
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Structural Changes in the Transition State of Protein Folding: Alternative Interpretations of Curved Chevron Plots
- 1999
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 38:20, s. 6499-6511
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Tidskriftsartikel (refereegranskat)abstract
- The interpretation of folding rates is often rationalized within the context of transition state theory. This means that the reaction rate is linked to an activation barrier, the height of which is determined by the free energy difference between a ground state (the starting point) and an apparent transition state. Changes in the folding kinetics are thus caused by effects on either the ground state, the transition state, or both. However, structural changes of the transition state are rarely discussed in connection with experimental data, and kinetic anomalies are commonly ascribed to ground state effects alone, e.g., depletion or accumulation of structural intermediates upon addition of denaturant. In this study, we present kinetic data which are best described by transition state changes. We also show that ground state effects and transition state effects are in general difficult to distinguish kinetically. The analysis is based on the structurally homologous proteins U1A and S6. Both proteins display two-state behavior, but there is a marked difference in their kinetics. S6 exhibits a classical V-shaped chevron plot (log observed rate constant vs denaturant concentration), whereas U1A's chevron plot is symmetrically curved, like an inverted bell curve. However, S6 is readily mutated to display U1A-like kinetics. The seemingly drastic effects of these mutations are readily ascribed to transition state movements where large kinetic differences result from relatively small alterations of a common free energy profile and broad activation barriers.
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| 15. |
- Persson, Roger, et al.
(författare)
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Relationship Between Changes in Workplace Bullying Status and the Reporting of Personality Characteristics
- 2016
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Ingår i: Journal of Occupational and Environmental Medicine. - 1536-5948. ; 58:9, s. 10-902
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine whether a shift in work-related bullying status, from being non-bullied to being bullied or vice versa, was associated with changes in reporting of personality characteristics.METHODS: Data on bullying and personality (neuroticism, extraversion, and sense of coherence) were collected in three waves approximately 2 years apart (N = 4947). Using a within-subjects design, personality change scores that followed altered bullying status were evaluated with one-sample t tests. Sensitivity analyses targeted depressive symptoms.RESULTS: Shifts from non-bullied to frequently bullied were associated with increased neuroticism or decreased sense of coherence manageability scores. Shifts from bullied to non-bullied were associated with decreasing neuroticism and increasing extraversion scores, or increasing sense of coherence meaningfulness and comprehensibility scores. Excluding depressive cases had minor effects.CONCLUSIONS: Bullying seems to some extent to affect personality scale scores, which thus seem sensitive to environmental and social circumstances.
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| 16. |
- Sejr-Hansen, Martin, et al.
(författare)
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Comparison of Quantitative Flow Ratio and Instantaneous Wave-Free Ratio for Immediate Assessment of Non-Culprit Lesions in Patients With ST-Segment Elevation Myocardial Infarction An iSTEMI Substudy
- 2018
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 72:13, s. B248-B249
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Quantitative flow ratio (QFR) is an angiography-based approach for in-procedure functional evaluation of coronary artery lesions. We evaluated the diagnostic performance of QFR with instantaneous wave-free ratio (iFR) in non-culprit lesions (NCLs) in patients with ST-segment elevation myocardial infarction (STEMI) and with staged fractional flow reserve (FFR) as reference standard.METHODS: This is a post-hoc analysis of the iSTEMI study. All NCLs were assessed with iFR in the acute setting and with iFR and FFR at staged (median 19 days) follow-up. QFR (Medis Medical Imaging bv., The Netherlands) was computed for all analyzable NCLs in a core lab by an investigator blinded to iFR and FFR results. Diagnostic cut-off values were 0.80 for QFR, 0.89 for iFR, and 0.80 for FFR.RESULTS: A total of 156 NCLs in 120 patients were included in the iSTEMI study. Paired iFR and FFR data were available for 146 NCls in 112 patients. Of these, QFR analysis was feasible in 103 (71 %) lesions assessed in the acute setting. Mean acute QFR was 0.800.13, acute iFR was 0.860.12, and staged FFR was 0.800.11. With staged FFR as reference standard, diagnostic accuracy was 84% (95%CI: 76-90) for acute QFR and 73% (95%CI: 66-83) for acute iFR (p¼0.09), area under the receiver operating curve (AUC) was 0.89 (95%CI: 0.82-0.95) vs. 0.77 (95%CI: 0.68-0.87) (p¼0.02), sensitivity was 83% (95%CI: 69-92) vs. 85% (95%CI: 73-92) (p¼0.79), specificity was 84% (95%CI: 72-92) vs. 64% (95%CI: 53-75) (p¼0.11), positive predictive value was 81% (95%CI: 57-82) vs. 70% (95%CI: 57-82)(p¼0.06), and negative predictive value was 86% (95%CI: 76-95) vs. 84% (95%CI: 69-91)(p¼0.37), for acute QFR and acute iFR, respectively.CONCLUSION: The diagnostic performance of acute QFR in post hocevaluation of NCLs in STEMI patients was at least similar to acuteassessment by iFR with staged procedure FFR as reference. QFR couldprovide an easy, safe and cost-effective solution to evaluate NCLs inthe acute phase, thus potentially reducing the number of unnecessaryfollow-up procedures.CATEGORIES IMAGING: Physiologic Lesion Assessment.
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| 17. |
- Sejr-Hansen, Martin, et al.
(författare)
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Quantitative flow ratio for immediate assessment of nonculprit lesions in patients with ST-segment elevation myocardial infarction—An iSTEMI substudy
- 2019
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Ingår i: Catheterization and Cardiovascular Interventions. - : Wiley. - 1522-1946 .- 1522-726X. ; 94:5, s. 686-692
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We evaluated the diagnostic performance of quantitative flow ratio (QFR) assessment of nonculprit lesions (NCLs) based on acute setting angiograms obtained in patients with ST-segment elevation myocardial infarction (STEMI) with QFR, fractional flow reserve (FFR), and instantaneous wave-free ratio (iFR) in the staged setting as reference. Background: QFR is an angiography-based approach for the functional evaluation of coronary artery lesions. Methods: This was a post-hoc analysis of the iSTEMI study. NCLs were assessed with iFR in the acute setting and with iFR and FFR at staged (median 13 days) follow-up. Acute and staged QFR values were computed in a core laboratory based on the coronary angiography recordings. Diagnostic cut-off values were ≤0.80 for QFR and FFR, and ≤0.89 for iFR. Results: Staged iFR and FFR data were available for 146 NCLs in 112 patients in the iSTEMI study. Among these, QFR analysis was feasible in 103 (71%) lesions assessed in the acute setting with a mean QFR value of 0.82 (IQR: 0.73–0.91). Staged QFR, FFR, and iFR were 0.80 (IQR: 0.70–0.90), 0.81 (IQR: 0.71–0.88), and 0.91 (IQR: 0.87–0.96), respectively. Classification agreement of acute and staged QFR was 93% (95%Cl: 87–99). The classification agreement of acute QFR was 84% (95%CI: 76–90) using staged FFR as reference and 74% (95%CI: 65–83) using staged iFR as reference. Conclusions: Acute QFR showed a very good diagnostic performance with staged QFR as reference, a good diagnostic performance with staged FFR as reference, and a moderate diagnostic performance with staged iFR as reference.
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| 18. |
- Tekpli, Xavier, et al.
(författare)
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An independent poor-prognosis subtype of breast cancer defined by a distinct tumor immune microenvironment
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- How mixtures of immune cells associate with cancer cell phenotype and affect pathogenesis is still unclear. In 15 breast cancer gene expression datasets, we invariably identify three clusters of patients with gradual levels of immune infiltration. The intermediate immune infiltration cluster (Cluster B) is associated with a worse prognosis independently of known clinicopathological features. Furthermore, immune clusters are associated with response to neoadjuvant chemotherapy. In silico dissection of the immune contexture of the clusters identified Cluster A as immune cold, Cluster C as immune hot while Cluster B has a pro-tumorigenic immune infiltration. Through phenotypical analysis, we find epithelial mesenchymal transition and proliferation associated with the immune clusters and mutually exclusive in breast cancers. Here, we describe immune clusters which improve the prognostic accuracy of immune contexture in breast cancer. Our discovery of a novel independent prognostic factor in breast cancer highlights a correlation between tumor phenotype and immune contexture.
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| 19. |
- Thim, Troels, et al.
(författare)
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Agreement between iFR and FFR in staged follow-up evaluation of non-culprit stenoses after ST-segment elevation myocardial infarction (iSTEMI substudy)
- 2017
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 70:18, s. B91-B91
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Classification agreement between instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) is approximately 80% in stable patients. It was recently shown that FFR guidance, as compared to iFR guidance, was associated with a higher risk of subsequent revascularization among patients with non- ST-segment elevation myocardial infarction. The classification agreement, and the impact of time interval, between iFR and FFR in the assessment of non-culprit lesions after recent ST-segment elevation myocardial infarction (STEMI) has not been described.METHODS: The iSTEMI study assessed agreement between iFR across non-culprit stenoses at the index procedure in patients with STEMI versus iFR and FFR at a follow-up angiography. The interval between STEMI and follow-up evaluation was at the discretion of the treating physicians. In this substudy, classification agreement between follow-up iFR and follow-up FFR was evaluated within groups defined according to follow-up time point after STEMI, i.e., <5days, 5-15days, and16 days. iFR<0.90 and FFR0.80 were considered hemodynamically significant.RESULTS: Among 120 patients with 157 non-culprit stenoses, follow-up iFR and FFR was available in 112 patients with 146 non-culprit stenoses. Median follow-up interval was 16 days (IQR 5-32 days). The overall classification agreement was 84%. With follow-up<5days after STEMI, there was classification agreement between iFR and FFR was in 27 of 35 (77%) non-culprit stenoses. With follow-up 5-15 after STEMI, there was classification agreement in 33 of 38 (86%) non-culprit stenoses. With follow-up 16 days after STEMI, there was classification agreement in 63 of 73 (86%) non-culprit stenoses. The observed differences in these proportions over time after STEMI were not statistically significant (<5versus5days, p¼0.19).CONCLUSION: Overall, classification agreement between iFR and FFR in the assessment of non-culprit lesions after STEMI was comparable to that observed in stable patients. Time interval between STEMI and follow-up evaluation may impact agreement between follow-up iFR and follow-up FFR, although the observed differences were not statistically significant.
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| 20. |
- Thim, Troels, et al.
(författare)
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Agreement between nonculprit stenosis follow-up iFR and FFR after STEMI (iSTEMI substudy)
- 2020
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Ingår i: BMC Research Notes. - : BioMed Central. - 1756-0500. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate agreement between instantaneous wave free ratio (iFR) and fractional flow reserve (FFR) for the functional assessment of nonculprit coronary stenoses at staged follow-up after ST-segment elevation myocardial infarction (STEMI).RESULTS: We measured iFR and FFR at staged follow-up in 112 STEMI patients with 146 nonculprit stenoses. Median interval between STEMI and follow-up was 16 (interquartile range 5-32) days. Agreement between iFR and FFR was 77% < 5 days after STEMI and 86% after ≥ 5 days (p = 0.19). Among cases with disagreement, the proportion of cases with hemodynamically significant iFR and non-significant FFR were different when assessed < 5 days (5 in 8, 63%) versus ≥ 5 days (3 in 15, 20%) after STEMI (p = 0.04). Overall classification agreement between iFR and FFR was comparable to that observed in stable patients. Time interval between STEMI and follow-up evaluation may impact agreement between iFR and FFR.
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| 21. |
- Thim, Troels, et al.
(författare)
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Instantaneous wave-free ratio cutoff values for nonculprit stenosis classification in patients with ST-segment elevation myocardial infarction (an iSTEMI substudy)
- 2020
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Ingår i: Coronary Artery Disease. - : Lippincott Williams & Wilkins. - 0954-6928 .- 1473-5830. ; 31:5, s. 411-416
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The instantaneous wave-free ratio cutoff value of <0.90 for hemodynamic significance of coronary stenoses has been validated in stable patients. We examined different cutoff values in the evaluation of nonculprit stenoses in patients with ST-segment elevation myocardial infarction.Methods: We measured instantaneous wave-free ratio across nonculprit stenoses in the acute setting and at follow-up in 120 patients with ST-segment elevation myocardial infarction and 157 nonculprit stenoses, of which, 113 patients with 147 nonculprit stenoses completed follow-up.Results: The prevalence of nonculprit stenosis hemodynamic significance was 52% in the acute setting and 41% at follow-up. With follow-up, instantaneous wave-free ratio as reference, acute instantaneous wave-free ratio >0.90 had a negative predictive value of 89%. Acute instantaneous wave-free ratio <0.90 had a positive predictive value of 68%. Acute instantaneous wave-free ratio >0.93 had a negative predictive value of 100%. Acute instantaneous wave-free ratio <0.86 and <0.83 had positive predictive values of 71 and 77%. Using acute instantaneous wave-free ratio <0.90 as cutoff for hemodynamic significance yielded the highest degree of classification agreement between acute and follow-up instantaneous wave-free ratio.Conclusions: In patients with ST-segment elevation myocardial infarction, acute instantaneous wave-free ratio with the cutoff values <0.90 for hemodynamic significance appears optimal in the evaluation of nonculprit stenoses and has a high negative predictive value and a moderate positive predictive value.
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- Thim, Troels, et al.
(författare)
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Nonculprit Stenosis Evaluation Using Instantaneous Wave-Free Ratio in Patients With ST-Segment Elevation Myocardial Infarction
- 2017
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Ingår i: JACC. - New York, USA : Elsevier. - 1936-8798 .- 1876-7605. ; 10:24, s. 2528-2535
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to examine the level of agreement between acute instantaneous wave-free ratio (iFR) measured across nonculprit stenoses in patients with ST-segment elevation myocardial infarction (STEMI) and iFR measured at a staged follow-up procedure.BACKGROUND: Acute full revascularization of nonculprit stenoses in STEMI is debated and currently guided by angiography. Acute functional assessment of nonculprit stenoses may be considered.METHODS: Immediately after successful primary culprit intervention for STEMI, nonculprit coronary stenoses were evaluated with iFR and left untreated. Follow-up evaluation with iFR was performed at a later stage. iFR <0.90 was considered hemodynamically significant.RESULTS: One hundred twenty patients with 157 nonculprit lesions were included. Median acute iFR was 0.89 (interquartile range: 0.82 to 0.94; n = 156), and median follow-up iFR was 0.91 (interquartile range [IQR]: 0.86 to 0.96; n = 147). Classification agreement was 78% between acute and follow-up iFR. The negative predictive value of acute iFR was 89%. Median time from acute to follow-up evaluation was 16 days (IQR: 5 to 32 days). With follow-up within 5 days after STEMI, no difference was observed between acute and follow-up iFR, and classification agreement was 89%. With follow-up ≥16 days after STEMI, acute iFR was lower than follow-up iFR, and classification agreement was 70%.CONCLUSIONS: Acute iFR evaluation appeared valid for ruling out significant nonculprit stenoses in patients with STEMI undergoing primary percutaneous coronary intervention. The time interval from acute to follow-up iFR influenced classification agreement, suggesting that inherent physiological disarrangements during STEMI may contribute to classification disagreement.
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