| 1. |
- Ederle, Joerg, et al.
(author)
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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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In: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Journal article (peer-reviewed)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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| 2. |
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| 3. |
- Robinson, N. A., et al.
(author)
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Applying genetic technologies to combat infectious diseases in aquaculture
- 2022
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In: Reviews in Aquaculture. - : Wiley. - 1753-5123 .- 1753-5131. ; 15:2, s. 491-535
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Journal article (peer-reviewed)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. |
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| 5. |
- Meisgen, S, et al.
(author)
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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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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 81:8, s. 1151-1161
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Journal article (peer-reviewed)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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| 6. |
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| 8. |
- Uhlin, F., et al.
(author)
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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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In: 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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Journal article (peer-reviewed)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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| 9. |
- Dizdarevic, A., et al.
(author)
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Intervention study to evaluate the importance of information given to patients with contact allergy : a randomized, investigator-blinded clinical trial*
- 2021
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In: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 184:1, s. 43-49
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Journal article (peer-reviewed)abstract
- Background: In contact dermatitis, it is crucial to understand and remember the outcome of patch testing. Unfortunately, many patients do not remember the results of their patch tests. Objectives: Our aim was to evaluate the effects of an intervention programme in which extensive information on specific contact allergy was provided, in individuals with positive patch test reactions. Methods: The study was designed as a randomized, investigator-blinded clinical trial. Participants with positive test reactions were randomized into two groups that received either standard information according to clinical routine or standard information and a reminder letter. Knowledge of contact allergies was evaluated using questionnaires 12 months after inclusion. Results: There were 184 adults included in the trial and the response rate at 1-year follow-up was 78% (143 of 184). Sixty-five per cent (45 of 69) in the intervention group and 54% (40 of 74) in the control group reported the correct name of the allergen (P = 0·23). Participants with several – as opposed to few – positive patch test reactions had difficulty in remembering the correct names of the allergens (P = 0·001). Moreover, the type of allergy had an influence on their ability to remember the name of the allergen correctly and their ability to make changes in lifestyle. Conclusions: The intervention performed did not significantly affect the participants’ ability to remember their contact allergy. To achieve better knowledge and changes in lifestyle, efforts to inform should concentrate on individuals with several positive patch test reactions, those with particular allergens, individuals over 60 years of age, and – concerning changes in lifestyle – males.
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| 10. |
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| 11. |
- Hoxha, A., et al.
(author)
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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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In: Clinical and Experimental Immunology. - : Wiley-Blackwell. - 0009-9104 .- 1365-2249. ; 186:3, s. 284-291
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Journal article (peer-reviewed)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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| 12. |
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| 13. |
- Mofors, J, et al.
(author)
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Comorbidity and long-term outcome in patients with congenital heart block and their siblings exposed to Ro/SSA autoantibodies in utero
- 2019
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:5, s. 696-703
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Journal article (peer-reviewed)abstract
- Congenital heart block (CHB) may develop in fetuses of Ro/SSA autoantibody-positive women. Given the rarity of CHB, information on comorbidity and complications later in life is difficult to systematically collect for large groups of patients. We therefore used nation-wide healthcare registers to investigate comorbidity and outcomes in patients with CHB and their siblings.MethodsData from patients with CHB (n= 119) and their siblings (n= 128), all born to anti-Ro/SSA-positive mothers, and from matched healthy controls (n= 1,190) and their siblings (n= 1,071), were retrieved from the Swedish National Patient Register. Analyses were performed by Cox proportional hazard modelling.ResultsIndividuals with CHB had a significantly increased risk of cardiovascular comorbidity, with cardiomyopathy and/or heart failure observed in 20 (16.8%) patients versus 3 (0.3%) controls, yielding a HR of 70.0 (95% CI 20.8 to 235.4), and with a HR for cerebral infarction of 39.9 (95% CI 4.5 to 357.3). Patients with CHB also had a higher risk of infections. Pacemaker treatment was associated with a decreased risk of cerebral infarction but increased risks of cardiomyopathy/heart failure and infection. The risk of systemic connective tissue disorder was also increased in patients with CHB (HR 11.8, 95% CI 4.0 to 11.8), and both patients with CHB and their siblings had an increased risk to develop any of 15 common autoimmune conditions (HR 5.7, 95% CI 2.83 to 11.69 and 3.6, 95% CI 1.7 to 8.0, respectively).ConclusionsThe data indicate an increased risk of several cardiovascular, infectious and autoimmune diseases in patients with CHB, with the latter risk shared by their siblings.
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| 14. |
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| 15. |
- Abdelhalim, Mohamed A., et al.
(author)
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Multicenter trans-Atlantic experience with fenestrated-branched endovascular aortic repair of chronic post-dissection thoracoabdominal aortic aneurysms
- 2023
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In: Journal of Vascular Surgery. - : Elsevier. - 0741-5214 .- 1097-6809. ; 78:4, s. 854-862.e1
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Journal article (peer-reviewed)abstract
- OBJECTIVE: This multicenter international study aimed to describe outcomes of fenestrated-branched endovascular aortic repairs (FB-EVAR) in a cohort of patients treated for chronic post-dissection thoracoabdominal aortic aneurysms (PD-TAAAs).METHODS: We reviewed the clinical data of all consecutive patients treated by FB-EVAR for repair of extent I to III PD-TAAAs in 16 centers from the United States and Europe (2008-2021). Data were extracted from institutional prospectively maintained databases and electronic patient records. All patients received off-the-shelf or patient-specific manufactured fenestrated-branched stent grafts. Endpoints were any cause mortality and major adverse events at 30 days, technical success, target artery (TA) patency, freedom from TA instability, minor (endovascular with <12 Fr sheath) and major (open or ≥12 Fr sheath) secondary interventions, patient survival, and freedom from aortic-related mortality (ARM).RESULTS: A total of 246 patients (76% male; median age, 67 years [interquartile range, 61-73 years]) were treated for extent I (7%), extent II (55%), and extent III (35%) PD-TAAAs by FB-EVAR. The median aneurysm diameter was 65 mm (interquartile range, 59-73 mm). Eighteen patients (7%) were octogenarians, 212 (86%) were American Society of Anesthesiologists class ≥3, and 21 (9%) presented with contained ruptured or symptomatic aneurysms. There were 917 renal-mesenteric vessels targeted by 581 fenestrations (63%) and 336 directional branches (37%), with a mean of 3.7 vessels per patient. Technical success was 96%. Mortality and rate of major adverse events at 30 days was 3% and 28%, including disabling complications such as new onset dialysis in 1%, major stroke in 1%, and permanent paraplegia in 2%. Mean follow-up was 24 months. Kaplan-Meier (KM) estimated patient survival at 3 and 5 years was 79% ± 6% and 65% ± 10%. KM estimated freedom from ARM was 95% ± 3% and 93% ± 5% at the same intervals. Unplanned secondary interventions were needed in 94 patients (38%), including minor procedures in 64 (25%) and major procedures in 30 (12%). There was one conversion to open surgical repair (<1%). KM estimated freedom from any secondary intervention was 44% ± 9% at 5 years. KM estimated primary and secondary TA patency were 93% ± 2% and 96% ± 1% at 5 years, respectively.CONCLUSIONS: FB-EVAR for chronic PD-TAAAs was associated with high technical success and a low rate of mortality (3%) and disabling complications at 30 days. Although the procedure is effective in the prevention of ARM, patient survival was low at 5 years (65%), likely due to the significant comorbidities in this cohort of patients. Freedom from secondary interventions at 5 years was 44%, although most procedures were minor. The significant rate of reinterventions highlights the need for continued patient surveillance.
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| 19. |
- Eriksson, S., et al.
(author)
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Antibacterial and antibiofilm effects of sodium hypochlorite against Staphylococcus aureus isolates derived from patients with atopic dermatitis
- 2017
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In: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963. ; 117:2, s. 513-521
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Journal article (peer-reviewed)abstract
- Background: Atopic dermatitis (AD) is characterized by an increased susceptibility to skin infections. Staphylococcus aureus is reported to dominate in AD lesions and reports have revealed the presence of staphylococcal biofilms. These infections contribute to aggravation of the eczema. Sodium hypochlorite is known to reduce bacterial load of skin lesions, as well as disease severity, in patients with AD, but the effect on biofilms is unknown. Objectives: To investigate the antimicrobial and antibiofilm effects of sodium hypochlorite against S. aureus isolates derived from patients with AD. Methods: Skin biopsies derived from patients with infected AD were examined by scanning electron microscopy (SEM). Using radial diffusion assays, biofilm assays and confocal laser scanning microscopy, we assessed the effect of sodium hypochlorite on S. aureus isolates derived from lesional skin of patients with AD. Results: SEM revealed clusters of coccoid bacteria embedded in fibrin and extracellular substances at the skin of a patient with infected AD. At concentrations of 0·01-0·08%, sodium hypochlorite showed antibacterial effects against planktonic cells. Eradication of S. aureus biofilms in vitro was observed in concentrations ranging from 0·01% to 0·16%. Confocal laser scanning microscopy confirmed these results. Finally, when human AD skin was subjected to sodium hypochlorite in an ex vivo model, a dose of 0·04% reduced the bacteria derived from AD skin. Conclusions: Sodium hypochlorite has antimicrobial and antibiofilm effects against clinical S. aureus isolates. Our findings suggest usage of a higher concentration than currently used in bleach baths of patients with skin-infected AD.
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| 20. |
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| 21. |
- Hallström, Elinor, et al.
(author)
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Climate impact of alcohol consumption in Sweden
- 2018
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In: Journal of Cleaner Production. - : Elsevier BV. - 0959-6526 .- 1879-1786. ; 201, s. 287-294
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Journal article (peer-reviewed)abstract
- Knowledge about the environmental impact of alcohol is limited and as an effect alcohol is often excluded from environmental studies of diets or included in incomplete ways. This paper describes the climate impact of beer, wine and liquor by using life cycle assessment. The climate impact is quantified per litre of specific alcoholic beverages and per total amount of alcohol consumed based on self-reported data of 50 000 individuals from 2009 within two population-based cohorts in Sweden. The results show that alcoholic beverages generate greenhouse gas (GHG) emissions in the range of 0.73–2.38 kg carbon dioxide equivalents (CO2e) per litre. Alcohol consumption in the population studied generates on average 52 kg CO2e per person and year. Within the 10% of the population with the highest intake of alcohol GHG emissions are up to 202 kg CO2e per person and year. Consumption of wine is responsible for the largest share of GHG emissions from alcoholic beverages (61%) followed by beer (33%), while liquor and strong wine account for a smaller share (6%). Alcohol consumption among men generates 90% higher GHG emissions than among women. Alcohol consumption and in consequence alcohol-related emissions are decreasing with increasing age of men and women. Our results indicate that alcohol consumption in Swedish men and women is responsible for an average of 3% of total diet-related GHG emissions and in sub-populations with the highest consumption up to 6–11%. Limiting alcohol could be an effective option to reduce the climate impact of diets, especially among men.
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| 22. |
- Hallström, Elinor, et al.
(author)
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Dietary climate impact : Contribution of foods and dietary patterns by gender and age in a Swedish population
- 2021
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In: Journal of Cleaner Production. - : Elsevier BV. - 0959-6526 .- 1879-1786. ; 306
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Journal article (peer-reviewed)abstract
- Dietary climate impact in a Swedish population (56–95 years old) was estimated based on self-reported food intake from 50 000 men and women within two population-based cohorts and on climate data, covering emissions from farm to fork, for 600 foods representative for the Swedish market. Aims were to assess variation in dietary climate impact between population groups and between food categories. Mean dietary climate impact was 2.0 tons of CO2e/person/year, with about a threefold variation between high and low impact individuals. Food loss and waste accounted for 18%. Older individuals and women on average had lower total dietary climate impact per year, while differences between gender were smaller per 1000 kcal. Climate impact was greatly affected by dietary composition and especially by the content of animal-based and discretionary foods, responsible for 71% and 12% of total climate impact, respectively. Results indicate a large potential for reduced climate impact by adopting realistic dietary patterns. Suggested strategies to reach climate goals include reduction of red meat and prioritising lower impact foods within meat, dairy and seafood categories, limited consumption of discretionary foods and decreased over-consumption of total calories, combined with improvements in production including reduction of food loss and waste.
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| 23. |
- Hallström, Elinor, et al.
(author)
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Dietary environmental impacts relative to planetary boundaries for six environmental indicators – A population-based study
- 2022
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In: Journal of Cleaner Production. - : Elsevier Ltd. - 0959-6526 .- 1879-1786. ; 373
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Journal article (peer-reviewed)abstract
- The environmental impact of Swedish diets was assessed for six indicators (greenhouse gas [GHG] emissions, cropland use, nitrogen application, phosphorus application, consumptive water use and extinction rate), using self-reported food intake within two population-based cohorts of men and women, 56–96 years of age. The dietary environmental impact was assessed in relation to per capita planetary boundaries, overall and by population subgroups, addressing the relative importance of specific foods and food groups. The total average dietary impact exceeded the planetary boundaries by 1.6 to 4-fold for five of the six environmental indicators; consumptive water use did not exceed the boundaries. Comparing the highest with lowest quintiles of the population impact showed >2.5-fold differences across all environmental indicators. Of the diet's total average environmental impact, animal-based, plant-based and discretionary foods accounted for 28–83%, 8–40% and 9–37%, respectively, across the six indicators. Animal-based foods dominated the impact on GHG emissions, cropland use and nitrogen and phosphorus application, while plant-based and discretionary foods contributed more to consumptive water use and extinction rate. Environmental impact was driven predominantly by consumption of red meat, dairy, fresh fruit and coffee. The findings show major challenges in affluent countries that have to be addressed to achieving sustainable food production systems and diets. They provide guidance on critical food groups, environmental indicators and population subgroups to prioritize in future efforts to reduce the environmental impact. © 2022 The Authors
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