| 1. |
- Böhm, Felix, et al.
(författare)
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FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction
- 2024
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 390:16, s. 1481-1492
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The benefit of fractional flow reserve (FFR)-guided complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease remains unclear. METHODS: In this multinational, registry-based, randomized trial, we assigned patients with STEMI or very-high-risk non-STEMI (NSTEMI) and multivessel disease who were undergoing primary percutaneous coronary intervention (PCI) of the culprit lesion to receive either FFR-guided complete revascularization of nonculprit lesions or no further revascularization. The primary outcome was a composite of death from any cause, myocardial infarction, or unplanned revascularization. The two key secondary outcomes were a composite of death from any cause or myocardial infarction and unplanned revascularization. RESULTS: A total of 1542 patients underwent randomization, with 764 assigned to receive FFR-guided complete revascularization and 778 assigned to receive culprit-lesion-only PCI. At a median follow-up of 4.8 years (interquartile range, 4.3 to 5.2), a primary-outcome event had occurred in 145 patients (19.0%) in the complete-revascularization group and in 159 patients (20.4%) in the culprit-lesion-only group (hazard ratio, 0.93; 95% confidence interval [CI], 0.74 to 1.17; P = 0.53). With respect to the secondary outcomes, no apparent between-group differences were observed in the composite of death from any cause or myocardial infarction (hazard ratio, 1.12; 95% CI, 0.87 to 1.44) or unplanned revascularization (hazard ratio, 0.76; 95% CI, 0.56 to 1.04). There were no apparent between-group differences in safety outcomes. CONCLUSIONS: Among patients with STEMI or very-high-risk NSTEMI and multivessel coronary artery disease, FFR-guided complete revascularization was not shown to result in a lower risk of a composite of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only PCI at 4.8 years. (Funded by the Swedish Research Council and others; FULL REVASC ClinicalTrials.gov number, NCT02862119.).
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| 2. |
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| 3. |
- Frodlund, Martina, et al.
(författare)
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The impact of immunomodulating treatment on the immunogenicity of COVID-19 vaccines in patients with immune-mediated inflammatory rheumatic diseases compared to healthy controls. : A Swedish nationwide study (COVID19-REUMA)
- 2023
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 41:20, s. 3247-3257
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To elucidate antibody responses after the second and third dose of COVID-19 vaccine in patients with inflammatory rheumatic diseases (IRD) treated with biologic/targeted disease modifying anti-rheumatic drugs (b/ts DMARDs).Methods: Antibody levels to antigens representing spike full length protein and spike S1 were measured before vaccination, 2-12 weeks after the second dose, before and after the third dose using multiplex bead-based serology assay. Positive antibody response was defined as antibody levels over cut off (seropositivity) in seronegative individuals or >= 4-fold increase in antibodies in individuals seropositive for both spike proteins.Results: Patients (n = 414) receiving b/ts DMARDs (283 had arthritis, 75 systemic vasculitis and 56 other autoimmune diseases) and controls (n = 61) from five Swedish regions participated. Treatments groups were: rituximab (n = 145); abatacept (n = 22); Interleukin 6 receptor inhibitors [IL6i (n = 79)]; JAnus Kinase Inhibitors [JAKi (n = 58)], Tumour Necrosis Factor inhibitor [TNFi (n = 68)] and Interleukin12/23/17 inhibitors [IL12/23/17i (n = 42)]. Percentage of patients with positive antibody response after two doses was significantly lower in rituximab (33,8%) and abatacept (40,9%) (p < 0,001) but not in IL12/23/17i, TNFi or JAKi groups compared to controls (80,3%). Higher age, ritux-imab treatment and shorter time between last rituximab course and vaccination predicted impaired anti-body response. Antibody levels collected 21-40 weeks after second dose decreased significantly (IL6i: p = 0,02; other groups: p < 0,001) compared to levels at 2-12 week but most participants remained seropositive. Proportion of patients with positive antibody response increased after third dose but was still significantly lower in rituximab (p < 0,001).Conclusions: Older individuals and patients on maintenance rituximab have an impaired response after two doses of COVID-19 vaccine which improves if the time between last rituximab course and vaccina-tion extends and also after an additional vaccine dose. Rituximab patients should be prioritized for (2023) booster vaccine doses. TNFi, JAKi and IL12/23/17i does not diminished humoral response to primary and an additional vaccination.
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| 4. |
- Holmberg, Kristina, et al.
(författare)
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The combination of work organizational climate and individual work commitment predicts return to work in women but not in men
- 2013
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Ingår i: Journal of Occupational and Environmental Medicine. - : Lippincott Williams & Wilkins. - 1076-2752 .- 1536-5948. ; 55:2, s. 121-127
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:: To analyze if the combination of organizational climate and work commitment can predict return to work (RTW). METHODS:: This prospective Swedish study was based on 2285 participants, 19 to 64 years old, consecutively selected from the employed population, newly sick-listed for more than 14 days. Data were collected in 2008 through postal questionnaire and from register data. RESULTS:: Among women, the combination of good organizational climate and fair work commitment predicted an early RTW with an adjusted relative risk of 2.05 (1.32 to 3.18). Among men, none of the adjusted variables or combinations of variables was found significantly to predict RTW. CONCLUSIONS:: This study demonstrated the importance of integrative effects of organizational climate and individual work commitment on RTW among women. These factors did not predict RTW in men. More research is needed to understand the RTW process among men.
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| 5. |
- Jakobsen Falk, Ingrid, et al.
(författare)
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Decreased survival in normal karyotype AML with single-nucleotide polymorphisms in genes encoding the AraC metabolizing enzymes cytidine deaminase and 5'-nucleotidase
- 2013
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Ingår i: American Journal of Hematology. - : John Wiley & Sons. - 0361-8609 .- 1096-8652. ; 88:12, s. 1001-1006
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Tidskriftsartikel (refereegranskat)abstract
- De novo acute myeloid leukemia with normal karyotype (NK-AML) comprises a large group of patients with no common cytogenetic alterations and with a large variation in treatment response. Single-nucleotide polymorphisms (SNPs) in genes related to the metabolism of the nucleoside analogue AraC, the backbone in AML treatment, might affect drug sensitivity and treatment outcome. Therefore, SNPs may serve as prognostic biomarkers aiding clinicians in individualized treatment decisions, with the aim of improving patient outcomes. We analyzed polymorphisms in genes encoding cytidine deaminase (CDA 79A>C rs2072671 and −451C>T rs532545), 5′-nucleotidase (cN-II 7A>G rs10883841), and deoxycytidine kinase (DCK 3′UTR 948T>C rs4643786) in 205 de novo NK-AML patients. In FLT3-internal tandem duplication (ITD)-positive patients, the CDA 79C/C and −451T/T genotypes were associated with shorter overall survival compared to other genotypes (5 vs. 24 months, P < 0.001 and 5 vs. 23 months, P = 0.015, respectively), and this was most pronounced in FLT3-ITD-positive/NPM1-positive patients. We observed altered in vitro sensitivity to topoisomerase inhibitory drugs, but not to nucleoside analogues, and a decrease in global DNA methylation in cells carrying both CDA variant alleles. A shorter survival was also observed for the cN-II variant allele, but only in FLT3-ITD-negative patients (25 vs. 31 months, P = 0.075). Our results indicate that polymorphisms in genes related to nucleoside analog drug metabolism may serve as prognostic markers in de novo NK-AML
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| 6. |
- Jakobsen Falk, Ingrid, et al.
(författare)
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Impact of ABCB1 single nucleotide polymorphisms 1236C>T and 2677G>T on overall survival in FLT3 wild-type de novo AML patients with normal karyotype
- 2014
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 167:5, s. 671-680
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Tidskriftsartikel (refereegranskat)abstract
- Drug resistance is a clinically relevant problem in the treatment of acute myeloid leukaemia (AML). We have previously reported a relationship between single nucleotide polymorphisms (SNPs) of ABCB1, encoding the multi-drug transporter P-glycoprotein, and overall survival (OS) in normal karyotype (NK)-AML. Here we extended this material, enabling subgroup analysis based on FLT3 and NPM1 status, to further elucidate the influence of ABCB1 SNPs. De novo NK-AML patients (n = 201) were analysed for 1199G>A, 1236C>T, 2677G>T/A and 3435C>T, and correlations to outcome were investigated. FLT3 wild-type 1236C/C patients have significantly shorter OS compared to patients carrying the variant allele; medians 20 vs. 49 months, respectively, P = 0.017. There was also an inferior outcome in FLT3 wild-type 2677G/G patients compared to patients carrying the variant allele, median OS 20 vs. 35 months, respectively, P = 0.039. This was confirmed in Cox regression analysis. Our results indicate that ABCB1 1236C>T and 2677G>T may be used as prognostic markers to distinguish relatively high risk patients in the intermediate risk FLT3 wild-type group, which may contribute to future individualizing of treatment strategies.
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| 7. |
- Johansson, Björn, et al.
(författare)
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Visual and optical performance of the Akreos Adapt Advanced Optics and Tecnis Z9000 intraocular lenses. Swedish multicenter study
- 2007
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Ingår i: Journal of cataract and refractive surgery. - : Ovid Technologies (Wolters Kluwer Health). - 0886-3350 .- 1873-4502. ; 33:9, s. 1565-1572
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To compare the subjective visual and objective optical performance of 2 aspherical intraocular lenses (lOLs), the Akreos Adapt Advanced Optics (AO) (Bausch & Lomb, Inc.) and the Tecnis Z9000 (Advanced Medical Optics, Inc.). SETTING: Four university hospitals in Sweden. METHODS: This study comprised 80 patients, 20 each from 4 university hospital centers in Sweden. All patients had bilateral clear corneal phacoemulsification with implantation of an Akreos Adapt AO IOL in 1 eye and Tecnis Z9000 IOL in the other eye according to a randomization protocol. Preoperatively, 90% contrast Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity was measured and the mesopic pupil sizes were determined. Ten to 12 weeks postoperatively, 12.5% and 90% contrast ETDRS visual acuities and photopic and mesopic Functional Acuity Contrast Test chart contrast sensitivities were determined. Wavefront analysis was performed with the Zywave II aberrometer (Bausch & Lomb, Inc.), and a questionnaire on the subjective quality of vision was completed by each patient. RESULTS: The Akreos AO IOL and Tecnis Z9000 IOL produced similar high- and low-contrast visual acuities as well as photopic and mesopic contrast sensitivities. The Tecnis Z9000 IOL resulted in lower spherical aberrations of the eye (mean 0.05 ± 0.13 μm versus 0.35 ± 0.13 μm root mean square, 6.0 mm pupil) (P<.001); however, the Akreos AO IOL provided a larger depth of field (mean 1.22 diopter [D] ± 0.48 [SD] versus 0.86 ± 0.50 D, 6.0 mm pupil) (P<.001). Patient satisfaction was generally high, although 68.8% of the patients reported some type of visual disturbance postoperatively. Twenty-eight percent of patients reported better subjective visual quality in the Akreos AO eye and 14%, in the Tecnis Z9000 eye (P<.0001). Accordingly, 33% perceived more visual disturbances in the Tecnis Z9000 eye and 11%, in the Akreos AO eye (P<.0001). CONCLUSIONS: Maximum reduction of spherical aberration did not maximize subjective visual quality. The higher perceived quality of vision with the Akreos AO IOL could be because of differences in depth of field, lOL material, or IOL design.
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| 8. |
- Karlsson, Johan, 1984, et al.
(författare)
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Stem cell homing using local delivery of plerixafor and stromal derived growth factor-1alpha for improved bone regeneration around Ti-implants
- 2016
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Ingår i: Journal of Biomedical Materials Research - Part A. - : Wiley. - 1552-4965 .- 1549-3296. ; 104:10, s. 2466-2475
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Tidskriftsartikel (refereegranskat)abstract
- Triggering of the early healing events, including the recruitment of progenitor cells, has been suggested to promote bone regeneration. In implantology, local drug release technologies could provide an attractive approach to promote tissue regeneration. In this study, we targeted the chemotactic SDF-1a/CXCR4 axis that is responsible e.g. for the homing of stem cells to trauma sites. This was achieved by local delivery of plerixafor, an antagonist to CXCR4, and/or SDF-1a from titanium implants coated with mesoporous titania thin films with a pore size of 7.5 nm. In vitro drug delivery experiments demonstrated that the mesoporous coating provided a high drug loading capacity and controlled release. The subsequent in vivo study in rat tibia showed beneficial effects with respect to bone-implant anchorage and bone-formation along the surface of the implants when plerixafor and SDF-1a were delivered locally. The effect was most prominent by the finding that the combination of the drugs significantly improved the mechanical bone anchorage. These observations suggest that titanium implants with local delivery of drugs for enhanced local recruitment of progenitor cells have the ability to promote osseointegration. This approach may provide a potential strategy for the development of novel implant treatments.
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| 9. |
- Klevebro, Susanna, et al.
(författare)
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Arachidonic acid and docosahexaenoic acid levels correlate with the inflammation proteome in extremely preterm infants
- 2024
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 0261-5614 .- 1532-1983. ; 43:5, s. 1162-1170
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Tidskriftsartikel (refereegranskat)abstract
- Background & aim: Clinical trials supplementing the long-chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA) and arachidonic acid (AA) to preterm infants have shown positive effects on inflammation-related morbidities, but the molecular mechanisms underlying these effects are not fully elucidated. This study aimed to determine associations between DHA, AA, and inflammation-related proteins during the neonatal period in extremely preterm infants. Methods: A retrospective exploratory study of infants (n = 183) born below 28 weeks gestation from the Mega Donna Mega trial, a randomized multicenter trial designed to study the effect of DHA and AA on retinopathy of prematurity. Serial serum samples were collected after birth until postnatal day 100 (median 7 samples per infant) and analyzed for phospholipid fatty acids and proteins using targeted proteomics covering 538 proteins. Associations over time between LCPUFAs and proteins were explored using mixed effect modeling with splines, including an interaction term for time, and adjusted for gestational age, sex, and center. Results: On postnatal day one, 55 proteins correlated with DHA levels and 10 proteins with AA levels. Five proteins were related to both fatty acids, all with a positive correlation. Over the first 100 days after birth, we identified 57 proteins to be associated with DHA and/or AA. Of these proteins, 41 (72%) related to inflammation. Thirty-eight proteins were associated with both fatty acids and the overall direction of association did not differ between DHA and AA, indicating that both LCPUFAs similarly contribute to up- and down-regulation of the preterm neonate inflammatory proteome. Primary examples of this were the inflammation-modulating cytokines IL-6 and CCL7, both being negatively related to levels of DHA and AA in the postnatal period. Conclusions: This study supports postnatal non-antagonistic and potentially synergistic effects of DHA and AA on the inflammation proteome in preterm infants, indicating that supplementation with both fatty acids may contribute to limiting the disease burden in this vulnerable population. Clinical registration number: ClinicalTrials.gov (NCT03201588).
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| 10. |
- Larsson, Jenny, 1974-, et al.
(författare)
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Anti-inflammatory effects of a titanium-peroxy gel: role of oxygen metabolites and apoptosis.
- 2004
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Ingår i: Journal of biomedical materials research. Part A. - : Wiley. - 1549-3296 .- 0021-9304 .- 1097-4636. ; 68:3, s. 448-57
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphonuclear neutrophils (PMN) are among the first inflammatory cells to arrive at an implant interface, where they encounter with the foreign material and may produce reactive oxygen species (ROS). During the interaction between titanium and ROS, titanium-peroxy (Ti-peroxy) compounds may be formed. We used a Ti-peroxy gel, made from titanium and hydrogen peroxide, to study the effects of Ti-peroxy compounds on PMN. In the absence of serum, the Ti-peroxy gel decreased the oxidative response of PMN to yeast and PMA and reduced PMN apoptosis without inducing necrosis. These effects could not be ascribed to the release of hydrogen peroxide from the Ti-peroxy gel, because a steady-state hydrogen peroxide producing system failed to mimic the effects of the gel. The effects were similarly unaffected when PMN were preincubated with beta(2)-integrin antibodies, questioning the involvement of adhesion molecules. Nevertheless, when a filter was used to separate the Ti-peroxy gel from the cells, the gel effect on PMN life span was abolished, pointing to a contact-dependent mechanism. In the presence of serum, the Ti-peroxy gel had no effect on the PMN oxidative response and life span, but appeared rather inert. In summary, this study demonstrates that the Ti-peroxy gel has potentially anti-inflammatory properties through a combined peroxide and physical contact effect, supporting the notion that interactions between titanium and inflammatory cells are responsible for the good performance of titanium in vivo.
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