| 1. |
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| 2. |
- Ederle, Joerg, et al.
(författare)
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Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
- 2010
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Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Tidskriftsartikel (refereegranskat)abstract
- Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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| 3. |
- Robinson, N. A., et al.
(författare)
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Applying genetic technologies to combat infectious diseases in aquaculture
- 2022
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Ingår i: Reviews in Aquaculture. - : Wiley. - 1753-5123 .- 1753-5131. ; 15:2, s. 491-535
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Tidskriftsartikel (refereegranskat)abstract
- Disease and parasitism cause major welfare, environmental and economic concerns for global aquaculture. In this review, we examine the status and potential of technologies that exploit genetic variation in host resistance to tackle this problem. We argue that there is an urgent need to improve understanding of the genetic mechanisms involved, leading to the development of tools that can be applied to boost host resistance and reduce the disease burden. We draw on two pressing global disease problems as case studies—sea lice infestations in salmonids and white spot syndrome in shrimp. We review how the latest genetic technologies can be capitalised upon to determine the mechanisms underlying inter- and intra-species variation in pathogen/parasite resistance, and how the derived knowledge could be applied to boost disease resistance using selective breeding, gene editing and/or with targeted feed treatments and vaccines. Gene editing brings novel opportunities, but also implementation and dissemination challenges, and necessitates new protocols to integrate the technology into aquaculture breeding programmes. There is also an ongoing need to minimise risks of disease agents evolving to overcome genetic improvements to host resistance, and insights from epidemiological and evolutionary models of pathogen infestation in wild and cultured host populations are explored. Ethical issues around the different approaches for achieving genetic resistance are discussed. Application of genetic technologies and approaches has potential to improve fundamental knowledge of mechanisms affecting genetic resistance and provide effective pathways for implementation that could lead to more resistant aquaculture stocks, transforming global aquaculture. © 2022 The Authors. Reviews in Aquaculture published by John Wiley & Sons Australia, Ltd.
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| 4. |
- Salomonsson, S., et al.
(författare)
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A Population-based Investigation of the Autoantibody Profile in Mothers of Children with Atrioventricular Block
- 2011
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Ingår i: Scandinavian Journal of Immunology. - Oxford : Blackwell Publishing. - 0300-9475 .- 1365-3083. ; 74:5, s. 511-517
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Tidskriftsartikel (refereegranskat)abstract
- The objective of the study was to investigate the antigen specificity and occurrence of individual autoantibodies in mothers of children diagnosed with atrioventricular (AV) block in a nation-wide setting. Patients with AV block detected before 15 years of age were identified using national quality registries as well as a network of pediatric and adult cardiologists and rheumatologists at the six university hospitals in Sweden. Patients with gross heart malformations, surgically or infectiously induced blocks were excluded. Blood samples were obtained from the mothers and maternal autoantibody profile, including the occurrence of antibodies against Ro52, Ro60, La, SmB, SmD, RNP-70k, RNP-A, RNP-C, CENP-C, Scl-70, Jo-1, ribosomal RNP and histones was investigated in 193 mothers of children with AV block by immunoblotting and ELISA. Autoantibody reactivity was detected in 48% (93/193) of the mothers of children with AV block. In autoantibody-positive mothers, the vast majority, 95% (88/93), had antibodies against Ro52, while 63% (59/93) had autoantibodies to Ro60 and 58% (54/93) had autoantibodies to La. In addition, 13% (12/93) of the autoantibody-positive mothers had antibodies to other investigated antigens besides Ro52, Ro60 and La, and of these anti-histone antibodies were most commonly represented, detected in 8% (7/93) of the mothers. In conclusion, this Swedish population-based study confirms that maternal autoantibodies may associate with heart block in the child. Further, our data demonstrate a dominant role of Ro52 antibodies in association with AV block.
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| 5. |
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| 6. |
- Meisgen, S, et al.
(författare)
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Auxilin is a novel susceptibility gene for congenital heart block which directly impacts fetal heart function
- 2022
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 81:8, s. 1151-1161
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Tidskriftsartikel (refereegranskat)abstract
- Neonatal lupus erythematosus (NLE) may develop after transplacental transfer of maternal autoantibodies with cardiac manifestations (congenital heart block, CHB) including atrioventricular block, atrial and ventricular arrhythmias, and cardiomyopathies. The association with anti-Ro/SSA antibodies is well established, but a recurrence rate of only 12%–16% despite persisting maternal autoantibodies suggests that additional factors are required for CHB development. Here, we identify fetal genetic variants conferring risk of CHB and elucidate their effects on cardiac function.MethodsA genome-wide association study was performed in families with at least one case of CHB. Gene expression was analysed by microarrays, RNA sequencing and PCR and protein expression by western blot, immunohistochemistry, immunofluorescence and flow cytometry. Calcium regulation and connectivity were analysed in primary cardiomyocytes and cells induced from pleuripotent stem cells. Fetal heart performance was analysed by Doppler/echocardiography.ResultsWe identified DNAJC6 as a novel fetal susceptibility gene, with decreased cardiac expression of DNAJC6 associated with the disease risk genotype. We further demonstrate that fetal cardiomyocytes deficient in auxilin, the protein encoded by DNAJC6, have abnormal connectivity and Ca2+ homoeostasis in culture, as well as decreased cell surface expression of the Cav1.3 calcium channel. Doppler echocardiography of auxilin-deficient fetal mice revealed cardiac NLE abnormalities in utero, including abnormal heart rhythm with atrial and ventricular ectopias, as well as a prolonged atrioventricular time intervals.ConclusionsOur study identifies auxilin as the first genetic susceptibility factor in NLE modulating cardiac function, opening new avenues for the development of screening and therapeutic strategies in CHB.
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| 7. |
- Colombo, P. E., et al.
(författare)
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Optimizing School Food Supply: Integrating Environmental, Health, Economic, and Cultural Dimensions of Diet Sustainability with Linear Programming
- 2019
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601 .- 1661-7827. ; 16:17
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Tidskriftsartikel (refereegranskat)abstract
- There is great potential for reducing greenhouse gas emissions (GHGE) from public-sector meals. This paper aimed to develop a strategy for reducing GHGE in the Swedish school food supply while ensuring nutritional adequacy, affordability, and cultural acceptability. Amounts, prices and GHGE-values for all foods and drinks supplied to three schools over one year were gathered. The amounts were optimized by linear programming. Four nutritionally adequate models were developed: Model 1 minimized GHGE while constraining the relative deviation (RD) from the observed food supply, Model 2 minimized total RD while imposing stepwise GHGE reductions, Model 3 additionally constrained RD for individual foods to an upper and lower limit, and Model 4 further controlled how pair-wise ratios of 15 food groups could deviate. Models 1 and 2 reduced GHGE by up to 95% but omitted entire food categories or increased the supply of some individual foods by more than 800% and were deemed unfeasible. Model 3 reduced GHGE by up to 60%, excluded no foods, avoided high RDs of individual foods, but resulted in large changes in food-group ratios. Model 4 limited the changes in food-group ratios but resulted in a higher number of foods deviating from the observed supply and limited the potential of reducing GHGE in one school to 20%. Cost was reduced in almost all solutions. An omnivorous, nutritionally adequate, and affordable school food supply with considerably lower GHGE is achievable with moderate changes to the observed food supply; i.e., with Models 3 and 4. Trade-offs will always have to be made between achieving GHGE reductions and preserving similarity to the current supply.
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| 8. |
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| 9. |
- Hjorth, Stephan, 1953, et al.
(författare)
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(3S)-3-(2,3-difluorophenyl)-3-methoxypyrrolidine (IRL752)-a Novel Cortical-Preferring Catecholamine Transmission- and Cognition-Promoting Agent
- 2020
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Ingår i: Journal of Pharmacology and Experimental Therapeutics. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0022-3565 .- 1521-0103. ; 374:3, s. 404-419
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Tidskriftsartikel (refereegranskat)abstract
- Here we describe for the first time the distinctive pharmacological profile for (35)-3-(2,3-difluorophenyI)-3-nnethoxypyrrolidine (IRL752), a new phenyl-pyrrolidine derivative with regioselective central nervous system transmission-enhancing properties. IRL752 (3.7-150 mu mol/kg, s.c.) was characterized through extensive in vivo studies using behavioral, tissue neurochemical, and gene expression as well as microdialysis methods. Behaviorally, the compound normalized tetrabenazine-induced hypo-activity, whereas it was unable to stimulate basal locomotion in normal animals or either accentuate or reverse hyperactivity induced by amphetamine or MK-801. IRL752 induced but minor changes in monoaminergic tissue neurochemistry across noradrenaline (NA)- and dopamine (DA)-dominated brain regions. The expression of neuronal activity-, plasticity-, and cognition-related immediate early genes (IEGs), however, increased by 1.5-fold to 2-fold. Furthermore, IRL752 dose-dependently enhanced cortical catecholamine dialysate output to 600%-750% above baseline, whereas striatal DA remained unaltered, and NA rose to similar to 250%; cortical and hippocampal dialysate acetylcholine (ACh) increased to similar to 250% and 190% above corresponding baseline, respectively. In line with this cortically preferential transmission-promoting action, the drug was also procognitive in the novel object recognition and reversal learning tests. In vitro neurotarget affinity and functional data coupled to drug exposure support the hypothesis that 5-hydroxytryptannine 7 receptor and alpha 2(C)-adrenoceptor antagonism are key contributors to the in vivo efficacy and original profile of IRL752. The cortical-preferring facilitatory impact on cate-cholamine (and ACh) neurotransmission, along with effects on IEG expression and cognition-enhancing features, are in line with the potential clinical usefulness of IRL752 in conditions wherein these aspects may be dysregulated, such as in axial motor and cognitive deficits in Parkinson disease. SIGNIFICANCE STATEMENT This report describes the distinctive preclinical profile of (3S)3-(2,3-difluorophenyI)-3-nnethoxypyrrolidine (IRL752). Its in vivo neurochemical, behavioral, microdialysis, and gene expression properties are consistent with a cortically regioselective facilitatory impact on catecholaminergic and cholinergic neurotransmission accompanied by cognitive impairment-reversing features. The pharmacological characteristics of IRL752 are in line with the clinical usefulness of IRL752 in conditions wherein these aspects may be dysregulated, such as in axial motor and cognitive deficits in Parkinson disease.
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| 10. |
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| 11. |
- Ottosson, L., et al.
(författare)
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Structurally derived mutations define congenital heart block-related epitopes within the 200-239 amino acid stretch of the Ro52 protein
- 2005
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 61:2, s. 109-118
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Tidskriftsartikel (refereegranskat)abstract
- Congenital heart block is a passively transferred autoimmune condition, which affects the children of mothers with Ro/SSA autoantibodies. During pregnancy, the antibodies are transported across the placenta and affect the fetus. We have previously demonstrated that antibodies directed to the 200-239 amino acid (aa) stretch of the Ro52 component of the Ro/SSA antigen correlate with the development of congenital heart block. In this report, we investigated the antibody-antigen interaction of this target epitope in detail at a molecular and structural level. Peptides representing aa 200-239 (p200) with structurally derived mutations were synthesized to define the epitopes recognized by two Ro52 human monoclonal antibodies, S3A8 and M4H1, isolated from patient-derived phage display libraries. Analyses by ELISA, circular dichroism and MALDI-TOF-MS demonstrate that the antibody recognition is dependent on a partly a-helical fold within the putative leucine zipper of the 200-239 aa stretch and that the two human anti-p200 monoclonal antibodies, M4H1 and S3A8, recognize different epitopic structures within the p200 peptide. In addition, we investigated the representation of each fine specificity within the sera of mothers with children born with congenital heart block, and in such sera, antibodies of the S3A8 idiotype were more commonly detected and at higher levels than M4H1-like antibodies.
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| 12. |
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| 13. |
- Ross, S E, et al.
(författare)
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Variation and control of growth-form in the moss Hylocomium splendens
- 2001
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Ingår i: Journal of Bryology. - 1743-2820. ; 23, s. 283-292
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Tidskriftsartikel (refereegranskat)abstract
- The moss Hylocomium splendens has both sympodial and monopodial forms of growth. One aim of this study was to document the growth-form of shoots from different populations. A further aim was to discover the extent to which genetic or environmental factors determine whether monopodial or sympodial growth-form is predominant in a population. Switching between growth-forms within shoots occurs in most populations. Populations in forest habitats in temperate to mid-Arctic environments have predominantly sympodial shoots whereas shoots of populations from tundra habitats, in high-Arctic environments or at high altitudes, are predominantly monopodial. Transplant experiments showed that sympodial and monopodial shoots can respond plastically, by changing growth-form to some extent in different environments, and that high nutrient availability is an important environmental factor in promoting sympodial growth-form. However, even after 14 years, transplants did not show the same variation in growth-form as shoots in natural populations at the transplant sites. This suggests that populations are also genetically differentiated with respect to growth-form.
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| 14. |
- Uhlin, F., et al.
(författare)
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Endopeptidase Cleavage of Anti-Glomerular Basement Membrane Antibodies in vivo in Severe Kidney Disease: An Open-Label Phase 2a Study
- 2022
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Ingår i: Journal of the American Society of Nephrology. - : Ovid Technologies (Wolters Kluwer Health). - 1046-6673 .- 1533-3450. ; 33:4, s. 829-838
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Tidskriftsartikel (refereegranskat)abstract
- Background The prognosis for kidney survival is poor in patients presenting with circulating anti-glomerular basement membrane (GBM) antibodies and severe kidney injury. It is unknown if treat-ment with an endopeptidase that cleaves circulating and kidney bound IgG can alter the prognosis.& nbsp;Methods An investigator-driven phase 2a one-arm study (EudraCT 2016-004082-39) was performed in 17 hospitals in five European countries. A single dose of 0.25 mg/kg of imlifidase was given to 15 adults with circulating anti-GBM antibodies and an eGFR < 15 ml/min per 1.73m(2). All patients received standard treatment with cyclophosphamide and corticosteroids, but plasma exchange only if autoantibodies rebounded. The primary outcomes were safety and dialysis independency at 6 months.& nbsp;Results At inclusion, ten patients were dialysis dependent and the other five had eGFR levels between 7 and 14 ml/min per 1.73m(2). The median age was 61 years (range 19-77), six were women, and six were also positive for anti-neutrophil cytoplasmic antibodies. Then 6 hours after imlifidase infusion, all patients had anti-GBM antibodies levels below the reference range of a prespecified assay. At 6 months 67% (ten out of 15) were dialysis independent. This is significantly higher compared with 18% (nine out of 50) in a historical control cohort (P < 0.001, Fisher's exact test). Eight serious adverse events (including one death) were reported, none assessed as probably or possibly related to the study drug.& nbsp;Conclusions In this pilot study, the use of imlifidase was associated with a better outcome compared with earlier publications, without major safety issues, but the findings need to be confirmed in a randomized controlled trial.
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| 15. |
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| 16. |
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| 17. |
- Herling, L., et al.
(författare)
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Automated analysis of fetal cardiac function using color tissue Doppler imaging
- 2018
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Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 52:5, s. 599-608
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate the feasibility of automated analysis of fetal myocardial velocity recordings obtained by color tissue Doppler imaging (cTDI). Methods This was a prospective cross-sectional observational study of 107 singleton pregnancies >= 41 weeks of gestation. Myocardial velocity recordings were obtained by cTDI in a long-axis four-chamber view of the fetal heart. Regions of interest were placed in the septum and the right (RV) and left (LV) ventricular walls at the level of the atrioventricular plane. Peak myocardial velocities and mechanical cardiac time intervals were measured both manually and by an automated algorithm and agreement between the two methods was evaluated. Results In total, 321 myocardial velocity traces were analyzed using each method. It was possible to analyze all velocity traces obtained from the LV, RV and septal walls with the automated algorithm, and myocardial velocities and cardiac mechanical time intervals could be measured in 96% of all traces. The same results were obtained when the algorithm was run repeatedly. The myocardial velocities measured using the automated method correlated significantly with those measured manually. The agreement between methods was not consistent and some cTDI parameters had considerable bias and poor precision. Conclusions Automated analysis of myocardial velocity recordings obtained by cTDI was feasible, suggesting that this technique could simplify and facilitate the use of cTDI in the evaluation of fetal cardiac function, both in research and in clinical practice.
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| 18. |
- Herling, L., et al.
(författare)
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Automated analysis of fetal cardiac function using color tissue Doppler imaging in second half of normal pregnancy
- 2019
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Ingår i: Ultrasound in Obstetrics and Gynecology. - : WILEY. - 0960-7692 .- 1469-0705. ; 53:3, s. 348-357
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Color tissue Doppler imaging (cTDI) is a promising tool for the assessment of fetal cardiac function. However, the analysis of myocardial velocity traces is cumbersome and time-consuming, limiting its application in clinical practice. The aim of this study was to evaluate fetal cardiac function during the second half of pregnancy and to develop reference ranges using an automated method to analyze cTDI recordings from a cardiac four-chamber view. Methods This was a cross-sectional study including 201 normal singleton pregnancies between 18 and 42weeks of gestation. During fetal echocardiography, a four-chamber view of the heart was visualized and cTDI was performed. Regions of interest were positioned at the level of the atrioventricular plane in the left ventricular (LV), right ventricular (RV) and septal walls of the fetal heart, to obtain myocardial velocity traces that were analyzed offline using the automated algorithm. Peak myocardial velocities during atrial contraction (Am), ventricular ejection (Sm) and rapid ventricular filling, i. e. early diastole (Em), as well as the Em/Am ratio, mechanical cardiac time intervals and myocardial performance index (cMPI) were evaluated, and gestational age-specific reference ranges were constructed. Results At 18 weeks of gestation, the peak myocardial velocities, presented as fitted mean with 95% CI, were: LV Am, 3.39 (3.09-3.70) cm/s; LV Sm, 1.62 (1.46-1.79) cm/s; LV Em, 1.95 (1.75-2.15) cm/s; septal Am, 3.07 (2.80-3.36) cm/s; septal Sm, 1.93 (1.81-2.06) cm/s; septal Em, 2.57 (2.32-2.84) cm/s; RV Am, 4.89 (4.59-5.20) cm/s; RV Sm, 2.31 (2.16-2.46) cm/s; and RV Em, 2.94 (2.69-3.21) cm/s. At 42weeks of gestation, the peak myocardial velocities had increased to: LV Am, 4.25 (3.87-4.65) cm/s; LV Sm, 3.53 (3.19-3.89) cm/s; LV Em, 4.55 (4.18-4.94) cm/s; septal Am, 4.49 (4.17-4.82) cm/s; septal Sm, 3.36 (3.17-3.55) cm/s; septal Em, 3.76 (3.51-4.03) cm/s; RV Am, 6.52 (6.09-6.96) cm/s; RV Sm, 4.95 (4.59-5.32) cm/s; and RV Em, 5.42 (4.99-5.88) cm/s. The mechanical cardiac time intervals generally remained more stable throughout the second half of pregnancy, although, with increased gestational age, there was an increase in duration of septal and RV atrial contraction, LV pre-ejection and septal and RV ventricular ejection, while there was a decrease in duration of septal postejection. Regression equations used for the construction of gestational age-specific reference ranges for peak myocardial velocities, Em/Am ratios, mechanical cardiac time intervals and cMPI are presented. Conclusion Peak myocardial velocities increase with gestational age, while the mechanical time intervals remain more stable throughout the second half of pregnancy. Using an automated method to analyze cTDI-derived myocardial velocity traces, it was possible to construct reference ranges, which could be used in distinguishing between normal and abnormal fetal cardiac function.
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| 19. |
- Hoxha, A., et al.
(författare)
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Identification of discrete epitopes of Ro52p200 and association with fetal cardiac conduction system manifestations in a rodent model
- 2016
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Ingår i: Clinical and Experimental Immunology. - : Wiley-Blackwell. - 0009-9104 .- 1365-2249. ; 186:3, s. 284-291
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Tidskriftsartikel (refereegranskat)abstract
- Congenital heart block (CHB) is a potentially lethal condition characterized by a third-degree atrioventricular block (AVB). Despite anti-Ro52 antibodies being detected in nearly 90% of mothers of affected children, CHB occurs in only 1-2% of anti-Ro/Sjogrens-syndrome-related antigen A (SSA) autoantibody-positive pregnancies. Maternal antibodies have been suggested to bind molecules crucial to fetal cardiac function; however, it remains unknown whether a single antibody profile associates with CHB or whether several specificities and cross-reactive targets exist. Here, we aimed to define further the reactivity profile of CHB-associated antibodies towards Ro52p200 (amino acid 200-239). We first analysed reactivity of a monoclonal anti-Ro52 antibody shown to induce AVB in rats (7.8C7) and of sera from anti-Ro52p200 antibody-positive mothers of children with CHB towards a panel of modified Ro52p200 peptides, and subsequently evaluated their potential to induce AVB in rats upon transfer during gestation. We observed that CHB maternal sera displayed a homogeneous reactivity profile targeting preferentially the C-terminal part of Ro52p200, in contrast to 7.8C7 that specifically bound the p200 N-terminal end. In particular, amino acid D233 appeared crucial to maternal antibody reactivity towards p200. Despite low to absent reactivity towards rat p200 and different binding profiles towards mutated rat peptides indicating recognition of different epitopes within Ro52p200, immunoglobulin (Ig)G purified from two mothers of children with CHB could induce AVB in rats. Our findings support the hypothesis that several fine antibody specificities and cross-targets may exist and contribute to CHB development in anti-Ro52 antibody-positive pregnancies.
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| 20. |
- Ivanchenko, M, et al.
(författare)
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Natural killer cells and type II interferon in Ro/SSA and La/SSB autoantibody-exposed newborns at risk of congenital heart block
- 2021
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 80:2, s. 194-202
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Tidskriftsartikel (refereegranskat)abstract
- Congenital heart block (CHB) with immune cell infiltration develops in the fetus after exposure to maternal Ro/La autoantibodies. CHB-related serology has been extensively studied, but reports on immune-cell profiles of anti-Ro/La-exposed neonates are lacking. In the current study, we characterised circulating immune-cell populations in anti-Ro/La+mothers and newborns, and explored potential downstream effects of skewed neonatal cell populations.MethodsIn total, blood from mothers (n=43) and neonates (n=66) was sampled at birth from anti-Ro/La+ (n=36) and control (n=30) pregnancies with or without rheumatic disease and CHB. Flow cytometry, microarrays and ELISA were used for characterising cells and plasma.ResultsSimilar to non-pregnant systemic lupus erythematosus and Sjögren-patients, anti-Ro/La+mothers had altered B-cell subset frequencies, relative T-cell lymphopenia and lower natural killer (NK)-cell frequencies. Surprisingly, their anti-Ro/La exposed neonates presented higher frequencies of CD56dimCD16hiNK cells (p<0.01), but no other cell frequency differences compared with controls. Type I and II interferon (IFN) gene-signatures were revealed in neonates of anti-Ro/La+ pregnancy, and exposure of fetal cardiomyocytes to type I IFN induced upregulation of several NK-cell chemoattractants and activating ligands. Intracellular flow cytometry revealed IFNγ production by NK cells, CD8+and CD4+T cells in anti-Ro/La exposed neonates. IFNγ was also detectable in their plasma.ConclusionOur study demonstrates an increased frequency of NK cells in anti-Ro/La exposed neonates, footprints of type I and II IFN and an upregulation of ligands activating NK cells in fetal cardiac cells after type I IFN exposure. These novel observations demonstrate innate immune activation in neonates of anti-Ro/La+pregnancy, which could contribute to the risk of CHB.
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| 21. |
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| 22. |
- Tsilimparis, Nikolaos, et al.
(författare)
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Transatlantic multicenter study on the use of a modified preloaded delivery system for fenestrated endovascular aortic repair
- 2023
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Ingår i: Journal of Vascular Surgery. - 0741-5214. ; 78:4, s. 3-873
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Analyze the outcomes of endovascular complex abdominal and thoracoabdominal aortic aneurysm repair using the Cook fenestrated device with the modified preloaded delivery system (MPDS) with a biport handle and preloaded catheters. Methods: A multicenter retrospective single arm cohort study was performed, including all consecutive patients with complex abdominal aortic aneurysm repair and thoracoabdominal aortic aneurysms treated with the MPDS fenestrated device (Cook Medical). Patient clinical characteristics, anatomy, and indications for device use were collected. Outcomes, classified according to the Society for Vascular Surgery reporting standards, were collected at discharge, 30 days, 6 months, and annually thereafter. Results: Overall, 712 patients (median age, 73 years; interquartile range [IQR], 68-78 years; 83% male) from 16 centers in Europe and the United States treated electively were included: 35.4% (n = 252) presented with thoracoabdominal aortic aneurysms and 64.6% (n = 460) with complex abdominal aortic aneurysm repair. Overall, 2755 target vessels were included (mean, 3.9 per patient). Of these, 1628 were incorporated via ipsilateral preloads using the MPDS (1440 accessed from the biport handle and 188 from above). The mean size of the contralateral femoral sheath during target vessel catheterization was 15F ± 4, and in 41 patients (6.7%) the sheath size was ≤8F. Technical success was 96.1%. Median procedural time was 209 minutes (IQR, 161-270 minutes), contrast volume was 100 mL (IQR, 70-150mL), fluoroscopy time was 63.9 minutes (IQR, 49.7-80.4 minutes) and median cumulative air kerma radiation dose was 2630 mGy (IQR, 838-5251 mGy). Thirty-day mortality was 4.8% (n = 34). Access complications occurred in 6.8% (n = 48) and 30-day reintervention in 7% (n = 50; 18 branch related). Follow-up of >30 days was available for 628 patients (88%), with a median follow-up of 19 months (IQR, 8-39 months). Branch-related endoleaks (type Ic/IIIc) were observed in 15 patients (2.6%) and aneurysm growth of >5 mm was observed in 54 (9.5%). Freedom from reintervention at 12 and 24 months was 87.1% (standard error [SE],1.5%) and 79.2% (SE, 2.0%), respectively. Overall target vessel patency at 12 and 24 months was 98.6% (SE, 0.3%) and 96.8% (SE, 0.4%), respectively, and was 97.9% (SE, 0.4%) and 95.3% (SE, 0.8%) for arteries stented from below using the MPDS, respectively. Conclusions: The MPDS is safe and effective. Overall benefits include a decrease in contralateral sheath size in the treatment of complex anatomies with favorable results.
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| 23. |
- Öhman, Annika, et al.
(författare)
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Transplantation-free survival after Norwood surgery for hypoplastic left heart syndrome with aortic atresia: A Swedish national cohort study
- 2020
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Ingår i: Cardiology in the Young. - : Cambridge University Press (CUP). - 1047-9511 .- 1467-1107. ; 30:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Norwood surgery has been available in Sweden since 1993. In this national cohort study, we analysed transplantation-free survival after Norwood surgery for hypoplastic left heart syndrome with aortic atresia. Methods: Patients were identified from the complete national cohort of live-born with hypoplastic left heart syndrome/aortic atresia 1993-2010. Analysis of survival after surgery was performed using Cox proportional hazards models for the total cohort and for birth period and gender separately. Thirty-day mortality and inter-stage mortality were analysed. Patients were followed until September 2016. Results: The 1993-2010 cohort consisted of 208 live-born infants. Norwood surgery was performed in 121/208 (58%). The overall transplantation-free survival was 61/121 (50%). The survival was higher in the late period (10-year survival 63%) than in the early period (10-year survival 40%) (p = 0.010) and lower for female (10-year survival 34%) than for male patients (10-year survival 59%) (p = 0.002). Inter-stage mortality between stages I and II decreased from 23 to 8% (p = 0.008). For male patients, low birthweight in relation to gestational age was a factor associated with poor outcome. Conclusion: The survival after Norwood surgery for hypoplastic left heart syndrome/aortic atresia improved by era of surgery, mainly explained by improved survival between stages I and II. Female gender was a significant risk factor for death or transplantation. For male patients, there was an increased risk of death when birthweight was lower than expected in relation to gestational age.
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