Egeberg A.,Herlev and Gentofte Hospital
Danish Medical Journal | Year: 2016
Psoriasis is a prevalent chronic inflammatory disease whose exact etiology is not fully understood, but both genetic and environmental factors have been implicated in the onset and progression of the disease. At the skin level, psoriasis is characterized by localized or widespread thick raised silvery-white scaling and pruritic plaques and studies have shown that psoriasis negatively affects patients’ quality of life, and depression occurs more often in patients with psoriasis. However, data have shown that psoriasis is a systemic disease which affects the joints, vasculature, and other tissues as well. Indeed, approximately one-third of patients with psoriasis develop psoriatic arthritis, and patients with severe psoriasis have a shortened life expectancy. Although our knowledge of the pathogenesis of psoriasis has advanced significantly in the past decade, as have the pharmacological treatment options which are now available, several important knowledge gaps re-main. Many of the proinflammatory mediators involved in psoriasis have also been implicated in some central nervous system (CNS) diseases. However, studies on associations between psoriasis and CNS diseases are scarce. Based on nationwide registry data from the entire Danish population, the present thesis examined the as-sociations between psoriasis and certain CNS diseases. The specific objectives of this work were to investigate the independent impact of depression on the risk of cardiovascular disease (CVD) in patients with psoriasis, the relationship between psoriasis and uveitis, and the risk of incident multiple sclerosis (MS) following the onset of psoriasis, respectively. The main results were a significantly increased risk of myocardial infarction (MI), stroke, and CV death in patients with psoriasis during stages of acute depression. Moreover, we found a bidirectional relationship between psoriasis and uveitis, where the occurrence of either disease significantly increased the risk of the other. Perhaps most notably, however, was that we found a psoriasis severity dependent increased risk of MS. In conclusion, psoriasis was significantly associated with certain CNS diseases, and the risk of CVD was strongly associated with acute depression in these patients. These novel findings suggest an important link between psoriasis and CNS diseases, and high-light the necessity for a holistic approach to the diagnosis and treatment of patients with psoriasis. © 2016, Danish Medical Association. All rights reserved.
Bay B.,University of Aarhus |
Bay B.,University of Cambridge |
Mortensen E.L.,Copenhagen University |
Golombok S.,University of Cambridge |
And 4 more authors.
Fertility and Sterility | Year: 2016
Objective: To study whether fertility treatment, subfertility, or pregnancy planning are related to long-term intellectual development. Design: Cohort study. Setting: Not applicable. Patient(s): A total of 5,032 singletons born from 1990 to 1992 in the Aarhus Birth Cohort were followed up to a mean age of 19 years. These children were born as a result of fertility treatment (n = 210), had subfertile parents who took more than 12 months before conceiving naturally (n = 334), had fertile parents who conceived naturally within 12 months (n = 2,661), or had parents who reported the pregnancy as unplanned (n = 1,827). Intervention(s): The children were followed up using questionnaires and information from Danish national registers. Main Outcome Measure(s): Parent reported school difficulties at ages 9-11 years, register-based school grades at ages 16, 17, and 19 years, and conscription intelligence test scores at age 19 years. Result(s): We found no evidence of school difficulties in childhood, impaired school performance in adolescence, or lower intelligence in young adulthood in multivariate analyses adjusted for parental age, educational level, maternal parity, before pregnancy body mass index (BMI), smoking and alcohol intake in pregnancy, cohabitation status, child gender, and age. Conclusion(s): In the longest follow-up of cognitive development of children conceived after fertility treatment or by subfertile parents conducted so far, this study did not show any association between pregnancy planning, subfertility, or fertility treatment and cognitive ability or academic performance. © 2016 American Society for Reproductive Medicine.
Pociot F.,Herlev and Gentofte Hospital |
Lernmark A.,Skane University Hospital
The Lancet | Year: 2016
Type 1 diabetes is diagnosed at the end of a prodrome of β-cell autoimmunity. The disease is most likely triggered at an early age by autoantibodies primarily directed against insulin or glutamic acid decarboxylase, or both, but rarely against islet antigen-2. After the initial appearance of one of these autoantibody biomarkers, a second, third, or fourth autoantibody against either islet antigen-2 or the ZnT8 transporter might also appear. The larger the number of β-cell autoantibody types, the greater the risk of rapid progression to clinical onset of diabetes. This association does not necessarily mean that the β-cell autoantibodies are pathogenic, but rather that they represent reproducible biomarkers of the pathogenesis. The primary risk factor for β-cell autoimmunity is genetic, mainly occurring in individuals with either HLA-DR3-DQ2 or HLA-DR4-DQ8 haplotypes, or both, but a trigger from the environment is generally needed. The pathogenesis can be divided into three stages: 1, appearance of β-cell autoimmunity, normoglycaemia, and no symptoms; 2, β-cell autoimmunity, dysglycaemia, and no symptoms; and 3, β-cell autoimmunity, dysglycaemia, and symptoms of diabetes. The genetic association with each one of the three stages can differ. Type 1 diabetes could serve as a disease model for organ-specific autoimmune disorders such as coeliac disease, thyroiditis, and Addison's disease, which show similar early markers of a prolonged disease process before clinical diagnosis. © 2016 Elsevier Ltd
The effects of psoriasis go far deeper than the skin: The condition may raise a person's risk of a potentially deadly aneurysm, a new study from Denmark finds. People in the study who had psoriasis — an inflammatory skin condition that causes red, scaly patches of skin — also had a greater risk of having an abdominal aortic aneurysm, according to the study, published today (April 14) in the journal Arteriosclerosis, Thrombosis and Vascular Biology. An abdominal aortic aneurysm is a relatively rare condition that occurs when the aorta, the large blood vessel that carries blood to the abdomen, becomes enlarged. If the enlarged aorta ruptures, it can be deadly, and there are often no symptoms of the aneurysm before a rupture occurs. The researchers found that as the severity of a person's psoriasis increased, so did the person's risk for an abdominal aortic aneurysm. [Heart Disease: Types, Prevention & Treatments] In the study, the researchers looked at nearly 60,000 people with mild psoriasis and more than 11,000 people with severe psoriasis. The researchers compared the risk of an aneurysm in each of these groups with the risk of having one among the 5.4 million people in the general population of Denmark, according to the study. Over a 14-year study period, 50 people with severe psoriasis, and 240 people with the mild form of the condition, developed an aneurysm. When the researchers took into account other factors that can affect people's risk of an aneurysm, such as their age and smoking history, they found that people with severe psoriasis had a 67 percent greater risk of developing an abdominal aortic aneurysm compared with the control group. People with mild psoriasis were also found to have an elevated risk: They were 20 percent more likely to develop the condition compared with the control group. This is not the first study to suggest that psoriasis may be linked to cardiovascular health. Psoriasis results from inflammation in the skin, and a 2015 study found that the skin condition was linked to the amount of inflammation in a person's blood vessels, which increases a person's risk for heart disease. In the new study, the researchers noted that inflammation in the aorta is necessary for the development of an aneurysm. Indeed, "psoriasis must be considered as a systemic inflammatory disease rather than an isolated skin disease," Dr. Usman Khalid, a cardiology researcher at Herlev and Gentofte Hospital in Denmark and the lead author of the study, said in a statement. [4 Common Skin Woes, and How to Fix Them] Because of this, patients with psoriasis should be more aware of their possible risk of cardiovascular diseases, including abdominal aortic aneurysms, Khalid said. More research is needed, however, to determine if patients with psoriasis should undergo additional screenings for aneurysms, he said. In addition, further research is required to determine if treating psoriasis with anti-inflammatory drugs may also reduce the risk of aneurysms, he said. Currently, there is no cure for psoriasis, but certain drugs can help patients manage their symptoms. Copyright 2016 LiveScience, a Purch company. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
Boisen M.K.,Herlev and Gentofte Hospital |
Dehlendorff C.,Danish Cancer Society |
Linnemann D.,Herlev and Gentofte Hospital |
Schultz N.A.,Rigshospitalet |
And 4 more authors.
BMC Cancer | Year: 2015
Background: Archival formalin-fixed paraffin-embedded (FFPE) cancer tissue samples are a readily available resource for microRNA (miRNA) biomarker identification. No established standard for reference miRNAs in FFPE tissue exists. We sought to identify stable reference miRNAs for normalization of miRNA expression in FFPE tissue samples from patients with colorectal (CRC) and pancreatic (PC) cancer and to quantify the variability associated with sample age and fixation. Methods: High-throughput miRNA profiling results from 203 CRC and 256 PC FFPE samples as well as from 37 paired frozen/FFPE samples from nine other CRC tumors (methodological samples) were used. Candidate reference miRNAs were identified by their correlation with global mean expression. The stability of reference genes was analyzed according to published methods. The association between sample age and global mean miRNA expression was tested using linear regression. Variability was described using correlation coefficients and linear mixed effects models. Normalization effects were determined by changes in standard deviation and by hierarchical clustering. Results: We created lists of 20 miRNAs with the best correlation to global mean expression in each cancer type. Nine of these miRNAs were present in both lists, and miR-103a-3p was the most stable reference miRNA for both CRC and PC FFPE tissue. The optimal number of reference miRNAs was 4 in CRC and 10 in PC. Sample age had a significant effect on global miRNA expression in PC (50% reduction over 20years) but not in CRC. Formalin fixation for 2-6 days decreased miRNA expression 30-65%. Normalization using global mean expression reduced variability for technical and biological replicates while normalization using the expression of the identified reference miRNAs reduced variability only for biological replicates. Normalization only had a minor impact on clustering results. Conclusions: We identified suitable reference miRNAs for future miRNA expression experiments using CRC- and PC FFPE tissue samples. Formalin fixation decreased miRNA expression considerably, while the effect of increasing sample age was estimated to be negligible in a clinical setting. © 2015 Boisen et al.