| 31. |
- Huang, X. F., et al.
(författare)
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Genomewide Association Study of Acute Anterior Uveitis Identifies New Susceptibility Loci
- 2020
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 61:6
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Acute anterior uveitis (AAU) is a common intraocular inflammatory disease. AAU occurs in 30% to 50% of patients with ankylosing spondylitis (AS), and both conditions are strongly associated with human leukocyte antigen (HLA)-B 27 , implying a shared etiology. This study aims to apply genomewide association study (GWAS) to characterize the genetic associations of AAU and their relationship to the genetics of AS. METHODS. We undertook the GWAS analyses in 2752 patients with AS with AAU (cases) and 3836 patients with AS without AAU (controls). There were 7,436,415 single-nucleotide polymorphisms (SNPs) available alter SNP microarray genotyping, imputation, and quality-control filtering. RESULTS. We identified one locus associated with AAU at genomewide significance: rs9378248 (P = 2.69 x 10(-8), odds ratio [OR] = 0.78), lying close to HLA-B. Suggestive association was observed at 11 additional loci, including previously reported AS loci ERAP1 (rs27529, P = 2.19 x 10(-7), OR = 1.22) and NOS2 (rs2274894, P = 8.22 x 10(-7), OR = 0.83). Multiple novel suggestive associations were also identified, including MERTK (rsl0171979, P = 2.56 x 10(-6), OR = 1.20), KIFAP3 (rs508063, P = 5.64 x 10(-7), OR = 1.20), CLCN7 (rs67412457, P = 1.33 x 10(-6), OR = 1.25), ACAA2 (rs9947182, P = 9.70 x 10(-7), OR = 1.37), and 5 intergenic loci. The SNP-based heritability is approximately 0.5 for AS alone, and is much higher (approximately 0.7) for AS with AAU. Consistent with the high heritability, a genomewide polygenic risk score shows strong power in identifying individuals at high risk of either AS with AAU or AS alone. CONCLUSIONS. We report here the first GWAS for AAU and identify new susceptibility loci. Our findings confirm the strong overlap in etiopathogenesis of AAU with AS, and also provide new insights into the genetic basis of AAU.
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| 32. |
- Ingvarsson, R. F., et al.
(författare)
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Good survival rates in systemic lupus erythematosus in southern Sweden, while the mortality rate remains increased compared with the population.
- 2019
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Ingår i: Lupus. - : SAGE Publications. - 1477-0962 .- 0961-2033. ; 28:12, s. 1488-1494
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Tidskriftsartikel (refereegranskat)abstract
- To ascertain the mortality rate and causes of death in patients with systemic lupus erythematosus (SLE) within a defined region in southern Sweden during the time period 1981-2014 and determine whether these have changed over time.In 1981, a prospective observation study of patients with SLE was initiated in southern Sweden. All incident SLE patients within a defined geographic area were identified using previously validated methods including diagnosis and immunology registers. Patients with a confirmed SLE diagnosis were then followed prospectively at the Department of Rheumatology in Lund. Clinical data was collected at regular visits. Patients were recruited from 1981 to 2006 and followed until 2014. The patient cohort was split into two groups based on the year of diagnosis to determine secular trends. Causes of death were retrieved from medical records and from the cause of death registry at The National Board of Health and Welfare in Sweden.In all, 175 patients were diagnosed with SLE during the study period. A total of 60 deaths occurred during a total of 3053 years of follow-up. In the first half of the study inclusion period 46 patients died, compared with 14 in the latter. The majority of patients (51.7%) died of cardiovascular disease. Infections caused 15% of the deaths and malignancy was the cause of death in 13.3% of patients. SLE was the main cause of death for 6.7% of the patients and a contributing factor for half of the patients. Standardized mortality ratio was increased in patients by a factor of 2.5 compared with the general population. Deaths occurred at an even rate throughout the whole observation period. No significant difference in standardized mortality ratio was observed between genders but was increased in older female patients. Furthermore, secular mortality trends were not identified.In this long-term epidemiologic follow-up study of incident SLE, we report a substantially raised mortality rate amongst SLE patients compared with the general population. The mortality rates have not changed significantly during the observation period that spanned three decades. The main cause of death was cardiovascular disease and this finding was consistent over time.
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| 33. |
- Klingberg, Eva, et al.
(författare)
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A distinct gut microbiota composition in patients with ankylosing spondylitis is associated with increased levels of fecal calprotectin
- 2019
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Ankylosing spondylitis (AS) shares many characteristics with inflammatory bowel disease (IBD). Intestinal microbiota most likely plays an important role in the development of IBDs and may also be involved in the pathogenesis of AS. We aimed to define and compare the fecal microbiota composition in patients with AS, ulcerative colitis (UC), and healthy controls (HC) and to determine relationships between fecal microbiota, fecal calprotectin, and disease-related variables in AS. Methods Fecal microbiota composition was assessed with GA-map (TM) Dysbiosis Test (Genetic Analysis, Oslo, Norway), which also reports the degree of deviation of the microbiota composition compared with a healthy control population, a Dysbiosis Index (DI) score 1-5. The AS patients were assessed with questionnaires, back mobility tests, fecal calprotectin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Results Totally, 150 patients with AS (55% men, median age 55.5 years, median BASDAI 3.2), 18 patients with UC (56% men, median age 30.5 years), and 17 HC (65% men, median age 22 years) were included. Principal component analysis showed highly separate clustering of fecal microbiota from the patients with AS, UC, and HC. Compared with HC, fecal microbiota in AS was characterized by a higher abundance of Proteobacteria, Enterobacteriaceae, Bacilli, Streptococcus species, and Actinobacteria, but lower abundance of Bacteroides and Lachnospiraceae. Further, fecal microbiota composition differed between patients with normal (<= 50 mg/kg, n = 57) and increased (>= 200 mg/kg, n = 36) fecal calprotectin. Patients with increased fecal calprotectin had lower abundance of bacteria with anti-inflammatory properties such as Faecalibacterium prausnitzii and Clostridium and higher abundance of the genus Streptococcus. No association was found between the fecal microbiota composition and HLAB27 status, disease activity, function, or medication. Dysbiosis (defined as DI >= 3) was found in 87% of AS patients. Conclusions Patients with AS have a distinct fecal microbiota signature, which is linked to fecal calprotectin levels, a marker of intestinal inflammation, but not to other clinical parameters. These findings suggest a local interplay between intestinal microbiota and gut inflammation in AS.
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| 34. |
- Rydenman, Karin, 1982, et al.
(författare)
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Tonsillectomy reduces the family impact of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome and improves health-related quality of life in affected children
- 2023
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Ingår i: Orphanet Journal of Rare Diseases. - 1750-1172. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is an autoinflammatory disorder that primarily affects young children, and typically gives rise to fever episodes that recur monthly for several years. This study investigated the impact of PFAPA syndrome on the families of affected children, the health-related quality of life (HRQOL) of children with the syndrome, and how these factors were influenced by tonsillectomy. Methods: This prospective cohort study included 24 children with typical PFAPA syndrome that were referred for tonsillectomy, of whom 20 underwent the procedure. The control group consisted of randomly selected children from the general population. Family impact and HRQOL were measured using the standardized, validated questionnaires Pediatric Quality of Life Inventory™ (PedsQL™) Family Impact Module (FIM) and PedsQL™ 4.0 Generic Core Scales (GCS). Parents to children with PFAPA completed the questionnaires before and 6 months after their child underwent tonsillectomy, and HRQOL was measured both between and during PFAPA episodes. The Wilcoxon signed-rank test was used to compare data before and after tonsillectomy in the patient group, while the Mann–Whitney test was used for comparison of the patient and control groups. Results: Before tonsillectomy, children with PFAPA had significantly lower scores than the control group on the PedsQL™ FIM and the PedsQL™ 4.0 GCS during fever episodes. After tonsillectomy, all patients improved with diminished febrile episodes, which resulted in significantly higher scores regarding both family impact and HRQOL at the time of follow-up. HRQOL of in children with PFAPA improved after tonsillectomy even when compared to afebrile intervals before the procedure. The differences between PFAPA patients and controls were eliminated after tonsillectomy. Conclusion: PFAPA syndrome has a profound negative impact on the families of affected children. Tonsillectomy that leads to cessation or reduction of fever episodes eases the impact of the disease on the family. HRQOL in children with PFAPA is low during febrile episodes and similar to healthy controls in between episodes. The improvement of HRQOL in patients with PFAPA after tonsillectomy compared to the afebrile intervals before tonsillectomy highlights that the constantly recurring fevers may affect the children’s well-being even between fever episodes.
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| 35. |
- Simard, Julia F, et al.
(författare)
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Lifestyle factors, autoimmune disease and family history in prognosis of non-hodgkin lymphoma overall and subtypes
- 2013
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 132:11, s. 2659-2666
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Tidskriftsartikel (refereegranskat)abstract
- Lifestyle factors and medical history are known to influence risk of non-Hodgkin lymphoma (NHL). Whether these factors affect the prognosis of NHL, especially its subtypes, is unclear. To investigate this, the association between these factors and all-cause and lymphoma-related mortality was assessed in a population-based cohort of 1,523 Swedish NHL patients included in the Scandinavian Lymphoma Etiology study in 1999-2002. Participants contributed time from NHL diagnosis until death or October 1, 2010, with virtually complete follow-up through linkage to the Swedish Cause of Death Register. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using stratified and multivariable-adjusted Cox regression models. During a median follow-up of 8.8 years, 670 patients (44%) died, with the majority of deaths attributed to lymphoma (86%). Current versus never smoking at diagnosis was associated with increased rate of all-cause death for all NHL (HR = 1.5, 1.2-1.8) and diffuse large B-cell lymphoma (HR = 1.8, 1.2-2.7). Low educational level (HR = 1.3, 1.1-1.7, <9 vs. >12 years) and NHL risk-associated autoimmune disease (HR = 1.4, 1.0-1.8) were associated with death for all NHL combined. However, evidence of an association with lymphoma-related death was limited. Body mass index, recent sunbathing and family history of hematopoietic malignancy were not consistently associated with death after NHL or its specific subtypes. These results add to the evidence that cigarette smoking, socioeconomic status and certain autoimmune diseases affect survival after NHL. Further investigations are needed to determine how these factors should be incorporated into clinical prognostic assessment.
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| 36. |
- Subramaniyam, Devipriya, et al.
(författare)
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TNF-alpha-induced self expression in human lung endothelial cells is inhibited by native and oxidized alpha 1-antitrypsin
- 2008
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Ingår i: International Journal of Biochemistry & Cell Biology. - : Elsevier BV. - 1878-5875 .- 1357-2725. ; 40:2, s. 258-271
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Tidskriftsartikel (refereegranskat)abstract
- Endothelial cells are among the main physiological targets of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). In endothelial cells TNF-alpha elicits a broad spectrum of biological effects including differentiation, proliferation and apoptosis. alpha 1-antitrypsin (AAT), an endogenous inhibitor of serine proteases plays a vital role in protecting host tissue from proteolytic injury at sites of inflammation. Recently, it has been shown that AAT can be internalized by pulmonary endothelial cells, raising speculation that it may modulate endothelial cell function in addition to suppressing protease activity. Using Affymetrix microarray technology, real time PCR and ELISA methods we have investigated the effects of AAT on un-stimulated and TNF-alpha stimulated human primary lung microvascular endothelial cell gene expression and protein secretion. We find that AAT and TNF-alpha generally induced expression of distinct gene families with AAT exhibiting little activity in terms of inflammatory gene expression. Approximately 25% of genes up regulated by TNF-alpha were inhibited by co-administration of AAT including TNF-alpha-induced self expression. Surprisingly, the effects of AAT on TNF-alpha-induced self expression was inhibited equally well by oxidized AAT, a modified form of AAT, which lacks serine protease inhibitor activity. Overall, the pattern of gene expression regulated by native and oxidized AAT was similar with neither inducing pro-inflammatory gene expression. These findings suggest that inhibitory effects of native and oxidized forms of AAT on TNF-alpha stimulated gene expression may play an important role in limiting the uncontrolled endothelial cell activation and vascular injury in inflammatory disease.
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| 37. |
- Sundberg, Frida, et al.
(författare)
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Children younger than 7 years with type 1 diabetes are less physically active than healthy controls.
- 2012
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - : Wiley. - 1651-2227 .- 0803-5253. ; 101:11, s. 1164-9
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To examine if children younger than 7years with type 1 diabetes are less physically active and spend more time sedentary than healthy children. Methods: Using a repeated measures case-control study design, physical activity (PA) was measured by continuous combined accelerometer and heart rate registration for 7days at two time points during 1year (autumn and spring). PA data were expressed as time spent sedentary, in moderate and vigorous intensity PA and total PA. Differences between groups and gender were analysed with mixed linear regression models. In this study there were 24 children (12 girls) with type 1 diabetes mellitus and 26 (14 girls) healthy controls, all younger than 7years at inclusion. Results: Children with diabetes were less active overall (p=0.010) and spent 16min less in moderate-to-vigorous PA (p=0.006). The difference in sedentary time (21min less) between groups was not significant (p=0.21). Overall PA (12.1 counts/min per day, p=0.004) and time in moderate and vigorous PA (16.0min/day, p=0.002) was significantly higher in boys than in girls. A significant effect of age was observed. Conclusion: Physical activity is significantly reduced in young children with type 1 diabetes.
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| 38. |
- Törnblom, Margareta, et al.
(författare)
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Development of radiographic knee osteoarthritis and the associations to radiographic changes and baseline variables in individuals with knee pain : a 2-year longitudinal study
- 2024
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Ingår i: BMJ Open. - London : BMJ Publishing Group Ltd. - 2044-6055. ; 14:3
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim was to study the development of radiographic knee osteoarthritis (RKOA) in individuals with knee pain over 2 years, and the associations between radiographic changes and baseline variables.Design: Longitudinal cohort study.Participants and setting: This study is part of the Halland Osteoarthritis cohort. The included 178 individuals, aged 30-67, had knee pain, without cruciate ligament injury or radiographic findings and 67% were women. The presence of RKOA was defined as Ahlbäck score of ≥1 in ≥1 knee. (Ahlbäck grade 1: joint space narrowing in the tibiofemoral joint <3 mm). Diagnosis of clinical KOA was based on the clinical guideline from the National Institute for Health and Care Excellence (NICE). Knee injury and Osteoarthritis Outcome Score (KOOS), pain intensity, physical function, body mass index (BMI) and visceral fat area (VFA) were measured. Associations to RKOA were analysed with logistic regression (OR).Results: In all, 13.8% (n=24) developed RKOA in 2 years whereof all had clinical KOA at baseline, as defined by NICE. Deterioration to RKOA was significantly associated with higher BMI, OR 1.119 (95% CI 1.024 to 1.223; p=0.013), and VFA, 1.008 (95% CI 1.000 to 1.016; p=0.049), worse knee pain intensity, 1.238 (95% CI 1.028 to 1.490; p=0.024), worse scores for KOOS Pain, 0.964 (95% CI 0.937 to 0.992; p=0.013) and KOOS Symptoms, 0.967 (95% CI 0.939 to 0.996; p=0.027), KOOS Activities of daily living 0.965 (95% CI 0.935 to 0.996; p=0.026) and KOOS Quality of Life 0.973 (95% CI 0.947 to 0.999; p=0.044), at baseline.Conclusions: One out of seven individuals with clinical KOA developed RKOA in only 2 years. Baseline variables associated with RKOA after 2 years may possibly be detected early by using the NICE guideline, assessment of obesity and self-reported data of symptoms to support first-line treatment: education, exercise and weight control. © Author(s) (or their employer(s)) 2024.
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| 39. |
- Westman, Gabriel, et al.
(författare)
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N-Methyl-D-Aspartate Receptor Autoimmunity Affects Cognitive Performance in Herpes Simplex Encephalitis
- 2016
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Ingår i: Clinical Microbiology And Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 22:11, s. 934-940
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the prevalence and temporal development of N-methyl-D-aspartate receptor (NMDAR) autoantibodies in relation to neurocognitive performance in patients with herpes simplex encephalitis (HSE). Methods: This prospective observational study enrolled a total of 49 HSE patients within a randomized controlled trial of valacyclovir. Cerebrospinal fluid and serum samples were drawn in the initial stage of disease, after 2 to 3 weeks and after 3 months. Anti-NMDAR IgG was detected with HEK293 cells transfected with plasmids encoding the NMDA NR1 type glutamate receptor. A batch of neurocognitive tests, including the Mattis Dementia Rating Scale (MDRS), Glasgow Coma Scale (GCS), Reaction Level Scale (RLS85), Mini-Mental State Examination (MMSE) and National Institutes of Health (NIH) stroke scale, was performed during 24 months' follow-up. Results: Anti-NMDAR IgG was detected in 12 of 49 participants. None were antibody positive in the initial stage of disease. In ten of 12 positive cases, specific antibodies were detectable only after 3 months. Notably, the development of NMDAR autoantibodies was associated with significantly impaired recovery of neurocognitive performance. After 24 months' follow-up, the median increase in MDRS total score was 1.5 vs. 10 points in antibody-positive and -negative participants (p = 0.018). Conclusions: Anti-NMDAR autoimmunity is a common complication to HSE that develops within 3 months after onset of disease. The association to impaired neurocognitive recovery could have therapeutical implications, as central nervous system autoimmunity is potentially responsive to immunotherapy.
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| 40. |
- Englund, Martin, et al.
(författare)
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Comorbidities in patients with antineutrophil cytoplasmic antibody-associated vasculitis versus the general population
- 2016
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 43:8, s. 1553-1558
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To evaluate the consultation rates of selected comorbidities in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) compared with the general population in southern Sweden. Methods. We used data from a population-based cohort of patients with AAV diagnosed between 1998 and 2010 in Southern Sweden (701,000 inhabitants). For each patient we identified 4 reference subjects randomly sampled from the general population and matched for year of birth, sex, area of residence, and index year. Using the population-based Skåne Healthcare Register, we identified relevant diagnostic codes, registered between 1998 and 2011, for selected comorbidities assigned after the date of diagnosis of AAV or the index date for the reference subjects. We calculated rate ratios for comorbidities (AAV:reference subjects). Results. There were 186 patients with AAV (95 women, mean age 64.5 yrs) and 744 reference persons included in the analysis. The highest rate ratios (AAV:reference) were obtained for osteoporosis (4.6, 95% CI 3.0-7.0), followed by venous thromboembolism (4.0, 95% CI 1.9-8.3), thyroid diseases (2.1, 95% CI 1.3-3.3), and diabetes mellitus (2.0, 95% CI 1.3-2.9). For ischemic heart disease, the rate ratio of 1.5 (95% CI 1.0-2.3) did not reach statistical significance. No statistically significant differences were found for cerebrovascular accidents. Conclusion. AAV is associated with increased consultation rates of several comorbidities including osteoporosis and thromboembolic and endocrine disorders. Comorbid conditions should be taken into consideration when planning and providing care for patients with AAV.
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