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- Dahlqvist, Johanna, 1979-, et al.
(författare)
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Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA
- 2022
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Ingår i: Rheumatology. - Oxford, United Kingdom : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:8, s. 3461-3470
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Tidskriftsartikel (refereegranskat)abstract
- Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. Results PR3-ANCA(+) AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 x 10(-61), odds ratio (OR) 0.10; rs9277341, P = 1.5 x 10(-44), OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 x 10(-10), OR 2.9). MPO-ANCA(+) AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 x 10(-25), OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 x 10(-7), OR 3.0), the latter a novel susceptibility locus for MPO-ANCA(+) granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. Conclusion We identified a novel susceptibility locus for MPO-ANCA(+) AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.
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| 2. |
- Ekman, Diana, et al.
(författare)
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Stratified genetic analysis reveals sex differences in MPO-ANCA-associated vasculitis
- 2023
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:9, s. 3213-3218
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To identify and genetically characterize subgroups of patients with ANCA-associated vasculitides (AAV) based on sex and ANCA subtype. Methods: A previously established SNP dataset derived from DNA sequencing of 1853 genes and genotyping of 1088 Scandinavian cases with AAV and 1589 controls was stratified for sex and ANCA subtype and analysed for association with five top AAV SNPs. rs9274619, a lead variant at the HLA-DQB1/HLA-DQA2 locus previously associated with AAV positive for myeloperoxidase (MPO)-ANCA, was analysed for association with the cumulative disease involvement of ten different organ systems. Results: rs9274619 showed a significantly stronger association to MPO-ANCA-positive females than males [P = 2.0 × 10-4, OR = 2.3 (95% CI 1.5, 3.5)], whereas proteinase 3 (PR3)-ANCA-associated variants rs1042335, rs9277341 (HLA-DPB1/A1) and rs28929474 (SERPINA1) were equally associated with females and males with PR3-ANCA. In MPO-ANCA-positive cases, carriers of the rs9274619 risk allele were more prone to disease engagement of eyes [P = 0.021, OR = 11 (95% CI 2.2, 205)] but less prone to pulmonary involvement [P = 0.026, OR = 0.52 (95% CI 0.30, 0.92)]. Moreover, AAV with both MPO-ANCA and PR3-ANCA was associated with the PR3-ANCA lead SNP rs1042335 [P = 0.0015, OR = 0.091 (95% CI 0.0022, 0.55)] but not with rs9274619. Conclusions: Females and males with MPO-ANCA-positive AAV differ in genetic predisposition to disease, suggesting at least partially distinct disease mechanisms between the sexes. Double ANCA-positive AAV cases are genetically similar to PR3-ANCA-positive cases, providing clues to the clinical follow-up and treatment of these patients.
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| 3. |
- Herlitz, Johan, 1949, et al.
(författare)
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Association between interval between call for ambulance and return of spontaneous circulation and survival in out-of-hospital cardiac arrest
- 2006
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 71:1, s. 40-6
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To describe the association between the interval between the call for ambulance and return of spontaneous circulation (ROSC) and survival in out-of-hospital cardiac arrest. PATIENTS: All patients suffering an out-of-hospital cardiac arrest in whom cardiopulmonary resuscitation (CPR) was started, included in the Swedish Cardiac Arrest Registry (SCAR) for whom information about the time of calling for an ambulance and the time of ROSC was available. RESULTS: Among 26,192 patients who were included in SCAR and were not witnessed by the ambulance crew, information about the time of call for an ambulance and the time of ROSC was available in 4847 patients (19%). There was a very strong relationship between the interval between call for an ambulance and ROSC and survival to one month. If the interval was less than or equal to 5 min, 47% survived to one month. If the interval exceeded 30 min, only 5% (n = 35) survived to one month. The vast majority of the latter survivors had a shockable rhythm either on admission of the rescue team or at some time during resuscitation. CONCLUSION: Among patients who have ROSC after an out-of-hospital cardiac arrest, there is a very strong association between the interval between the call for ambulance and ROSC and survival to one month. However, even if this delay is very long (> 30 min after calling for an ambulance), a small percentage will ultimately survive; they are mainly patients who at some time during resuscitation have a shockable rhythm. The overall percentage of patients for whom CPR continued for more than 30 min who are alive one month later can be assumed to be extremely low.
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| 4. |
- Herlitz, Johan, 1949, et al.
(författare)
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Characteristics and outcome amongst young adults suffering from out-of-hospital cardiac arrest in whom cardiopulmonary resuscitation is attempted
- 2006
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Ingår i: J Intern Med. - : Wiley. - 0954-6820 .- 1365-2796. ; 260:5, s. 435-41
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Amongst patients suffering from out-of-hospital cardiac arrest, young adults represent a minority. However, these victims suffer from the catastrophe when they are in a very active phase of life and have a long life expectancy. This survey aims to describe young adults in Sweden who suffer from out-of-hospital cardiac arrest and in whom cardiopulmonary resuscitation (CPR) is attempted in terms of characteristics and outcome. DESIGN: Prospective and descriptive design. SUBJECTS AND METHODS: Young adults (18-35 years) who suffered from out-of-hospital cardiac arrest in whom CPR was attempted and who were included in the Swedish Cardiac Arrest Registry between 1990 and 2004. MAIN OUTCOME MEASURES: Survival to 1 month. RESULTS: In all, 1105 young adults (3.1% of all the patients in the registry) were included, of which 29% were females, 51% were nonwitnessed and 15% had a cardiac aetiology. Only 17% were found in ventricular fibrillation, 53% received bystander CPR. The overall survival to 1 month was 6.3%. High survival was found amongst patients found in ventricular fibrillation (20.8%) and those with a cardiac aetiology (14.8%). Ventricular fibrillation at the arrival of the rescue team remained an independent predictor of an increased chance of survival (odds ratio: 7.43; 95% confidence interval: 3.44-16.65). CONCLUSION: Amongst young adults suffering from out-of-hospital cardiac arrest and in whom CPR was attempted, a minority survived to 1 month. Subgroups with a higher survival could be defined (patients found in ventricular fibrillation and patients in whom there was a cardiac aetiology). However, only one independent predictor of an increased chance of survival could be demonstrated, i.e. ventricular fibrillation at the arrival of the rescue team.
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| 5. |
- Herlitz, Johan, 1949, et al.
(författare)
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Major differences in 1-month survival between hospitals in Sweden among initial survivors of out-of-hospital cardiac arrest
- 2006
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 70:3, s. 404-9
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To explore the rate of survival to hospital discharge among patients who were brought to hospital alive after an out-of-hospital cardiac arrest in different hospitals in Sweden. PATIENTS AND METHODS: All patients who had suffered an out-of-hospital cardiac arrest which was not witnessed by the ambulance crew, in whom cardiopulmonary resuscitation (CPR) was started and who had a palpable pulse on admission to hospital were evaluated for inclusion. Each participating ambulance organisation and its corresponding hospital(s) required at least 50 patients fulfilling these criteria. RESULTS: Three thousand eight hundred and fifty three patients who were brought to hospital by 21 different ambulance organisations fulfilled the inclusion criteria. The number of patients rescued by each ambulance organisation varied between 55 and 900. The survival rate, defined as alive 1 month after cardiac arrest, varied from 14% to 42%. When correcting for dissimilarities in characteristics and factors of the resuscitation, the adjusted odds ratio for survival to 1 month among patients brought to hospital alive in the three ambulance organisations with the highest survival versus the three with the lowest survival was 2.63 (95% CI: 1.77-3.88). CONCLUSION: There is a marked variability between hospitals in the rate of 1-month survival among patients who were alive on hospital admission after an out-of-hospital cardiac arrest. One possible contributory factor is the standard of post-resuscitation care.
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