| 1. |
- Thunström, Sofia, et al.
(författare)
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Aortic size predicts aortic dissection in Turner syndrome - A 25-year prospective cohort study
- 2023
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 373, s. 47-54
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Tidskriftsartikel (refereegranskat)abstract
- Background: Women with Turner syndrome (TS) have an increased risk of aortic dissection. The current recommended cutoff to prevent aortic dissection in TS is an aortic size index (ASI) of ≥2.5 cm/m2. This study estimated which aortic size had the best predictive value for the risk of aortic dissection, and whether adjusting for body size improved risk prediction. Methods: A prospective, observational study in Sweden, of women with TS, n = 400, all evaluated with echocardiography of the aorta and data on medical history for up to 25 years. Receiver operating characteristic (ROC) curves, sensitivity and specificity were calculated for the absolute ascending aortic diameter (AAD), ascending ASI and TS specific z-score. Results: There were 12 patients (3%) with aortic dissection. ROC curves demonstrated that absolute AAD and TS specific z-score were superior to ascending ASI in predicting aortic dissection. The best cutoff for absolute AAD was 3.3 cm and 2.12 for the TS specific z-score, respectively, with a sensitivity of 92% for both. The ascending ASI cutoff of 2.5 cm/m2 had a sensitivity of 17% only. Subgroup analyses in women with an aortic diameter ≥ 3.3 cm could not demonstrate any association between karyotype, aortic coarctation, bicuspid aortic valve, BMI, antihypertensive medication, previous growth hormone therapy or ongoing estrogen replacement treatment and aortic dissection. All models failed to predict a dissection in a pregnant woman. Conclusions: In Turner syndrome, absolute AAD and TS-specific z-score were more reliable predictors for aortic dissection than ASI. Care should be taken before and during pregnancy.
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| 4. |
- Bjurulf, Björn, 1962, et al.
(författare)
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Dravet syndrome in children - A population-based study
- 2022
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Ingår i: Epilepsy Research. - : Elsevier BV. - 0920-1211 .- 1872-6844. ; 182
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim was to describe age at diagnosis, cumulative incidence, SCN1A variants, mortality, seizure types and treatments in children with Dravet Syndrome (DS) in Sweden. Methods: Children diagnosed with DS, born between January 1st 2000 and December 31st 2018 were included in a population-based study. Clinical data, frequency of seizure types and treatments were collected from caregivers and medical records in 42 children. Age at diagnosis, cumulative incidence and treatment were compared between children born in Sweden 2000–2009 and 2010–2018. Results: We identified 55 children with DS, 53 were born in Sweden. Three children had died of definite, probable, or possible sudden unexpected death in epilepsy, one of acute anoxic brain injury and three of pneumonia or pneumonitis. Median age at death was 4.7 (range 3.3–11) years. In 49/53 children with known SCN1A status, a pathogenic/likely pathogenic variant of SCN1A was detected. In two a SCN1A variant of unknown significance was found. For children born in Sweden 2010–2018, median age at DS diagnosis was lower (1.6 vs 4.5 years, p = 0.001) and cumulative incidence higher (1/33,000 vs 1/46,000 live-born children, p = 0.03), compared to children born in 2000–2009. The most common seizure types were focal to bilateral tonic clonic (n = 41/42) and myoclonic (n = 35/42). Tonic seizures were reported in 25/42 children. Sodium-channel inhibitors had been used in 9/24 children born in 2010–2018 and 17/18 children born in 2000–2009 (p = 0.001). Significance: A SCN1A variant that could explain the syndrome was found in over 90% of children. Tonic seizures seem to be more frequent than earlier described. Median age at diagnosis was lower, cumulative incidence higher and use of contra-indicated sodium-channel inhibitors less common for children born in 2010–2018 compared with children born in 2000–2009. This could indicate an increased awareness of DS.
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| 5. |
- Hammarsten, Ola, et al.
(författare)
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Clinical measurement of cellular DNA damage hypersensitivity in patients with DNA repair defects
- 2022
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Ingår i: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: DNA repair deficiency disorders are rare inherited diseases arising from pathogenic (disease-causing) variants in genes involved in DNA repair. There are no standardized diagnostic assays for the investigation of pathological significance of unknown variants in DNA repair genes. We hypothesized that our assays for measuring in vitro patient blood cell hypersensitivity to DNA-damaging agents can be used to establish the pathological significance of unknown variants in DNA repair genes. Six patients with variants in the DNA repair genes PRKDC (two siblings), DCLRE1C (two siblings), NBN, and MSH6 were included. Here, we used the cell division assay (CDA) and the gamma-H2AX assay, which were both developed and clinically validated by us, to measure patient cell hypersensitivity in response to ionizing radiation, mitomycin C, cytarabine and doxorubicin. Results: Radiation hypersensitivity was detected in the two patients with variants in the PRKDC gene (p < 0.0001 for both at 3.5 Gy), and the two patients with DCLRE1C variants (p < 0.0001 at 3.5 Gy for sibling 1 and p < 0.0001 at 1 Gy for sibling 2). The cells from the patients with the PRKDC variant were also deficient in removing gamma-H2AX (p < 0.001). The cells from the patient with variants in the NBN gene were hypersensitive to mitomycin C (p = 0.0008) and deficient in both induction and removal of gamma-H2AX in response to radiation. Conclusions: The combination of the CDA and the gamma-H2AX assay is useful in investigating the significance of unknown variants in some DNA repair genes.
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| 6. |
- Hammarsten, Ola, et al.
(författare)
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Use of the cell division assay to diagnose Fanconi anemia patients' hypersensitivity to mitomycin C
- 2021
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Ingår i: Cytometry Part B-Clinical Cytometry. - : Wiley. - 1552-4949 .- 1552-4957. ; 100:3, s. 1894-1906
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Tidskriftsartikel (refereegranskat)abstract
- The recently reported cell division assay (CDA) was optimized to measure the relative sensitivity of cells to cytotoxic drugs in vitro. Here, we investigated the in vitro hypersensitivity of lymphocytes from Fanconi anemia (FA) patients, to cytotoxic drugs using CDA. Peripheral blood mononuclear cells (PBMC) as well as cell lines derived from FA patients were treated with two DNA interstrand crosslinking (ICL) agents, mitomycin C and cyclophosphamide. Our data indicate that the CDA detects hypersensitivity of cells from FA patients to mitomycin C. Further, cell lines derived from FA-patients were also hypersensitive to mitomycin C as well as cyclophosphamide, when assayed by the CDA. This study suggests that the CDA is a useful alternative for the diagnosis of FA patients' hypersensitivity to ICL agents.
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| 7. |
- Naessen, Sabine, et al.
(författare)
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Autoimmune Disease in Turner Syndrome in Sweden : An up to 25 Years' Controlled Follow-up Study
- 2024
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine Society. - 0021-972X .- 1945-7197. ; 109:2, s. e602-e612
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Tidskriftsartikel (refereegranskat)abstract
- Context: Turner syndrome (TS) is the most common chromosomal aberration in women; it is the result of structural or numeric abnormalities in the X chromosome. Autoimmune hypothyroidism has been recognized as one of the more prominent disorders associated with TS.Objective: This work aimed to study the prevalence of autoimmune diseases in TS.Methods: A cross-sectional, longitudinal, 25-year follow-up study was conducted of patients from adult Turner centers at the University Hospitals, Sweden. During 1994 to 2020, a total of 503 women aged 16 to 71 years with TS were evaluated consecutively every fifth year according to national guidelines. A random population sample of women, n = 401, aged 25 to 44 years, from the World Health Organization Monitoring of Trends and Determinants for Cardiovascular Disease (MONICA) project served as controls. Serum thyrotropin, free thyroxine, vitamin B-12, antithyroid peroxidase (anti-TPO), and antitransglutaminase antibodies were measured.Results: Mean follow-up time (years) was 16 +/- 7 for patients and 13 +/- 1 for controls. From study start, the prevalence increased in TS for hypothyroidism 40% to 58%, vitamin B-12 deficiency 5% to 12%, celiac disease 4% to 7%, positive anti-TPO 26% to 41%, and antitransglutaminase antibodies 6% to 8% (P < .0001 vs controls). Type 1 diabetes and Addison disease were rare. The only interrelationship was between hypothyroidism and vitamin B-12 deficiency, both in TS and controls. No association between autoimmune disease and karyotype, antecedent growth hormone treatment, or ongoing estrogen hormone replacement, was seen in TS.Conclusion: In women with TS up to older than 80 years, more than half developed hypothyroidism, mainly autoimmune, during follow-up. Awareness of vitamin B-12 deficiency and celiac disease throughout life is also recommended in women with TS.
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| 8. |
- Sederholm Lawesson, Sofia, 1973-, et al.
(författare)
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Association Between History of Adverse Pregnancy Outcomes and Coronary Artery Disease Assessed by Coronary Computed Tomography Angiography.
- 2023
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Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 329:5, s. 393-404
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Tidskriftsartikel (refereegranskat)abstract
- Adverse pregnancy outcomes are recognized risk enhancers for cardiovascular disease, but the prevalence of subclinical coronary atherosclerosis after these conditions is unknown.To assess associations between history of adverse pregnancy outcomes and coronary artery disease assessed by coronary computed tomography angiography screening.Cross-sectional study of a population-based cohort of women in Sweden (n=10528) with 1 or more deliveries in 1973 or later, ascertained via the Swedish National Medical Birth Register, who subsequently participated in the Swedish Cardiopulmonary Bioimage Study at age 50 to 65 (median, 57.3) years in 2013-2018. Delivery data were prospectively collected.Adverse pregnancy outcomes, including preeclampsia, gestational hypertension, preterm delivery, small-for-gestational-age infant, and gestational diabetes. The reference category included women with no history of these exposures.Coronary computed tomography angiography indexes, including any coronary atherosclerosis, significant stenosis, noncalcified plaque, segment involvement score of 4 or greater, and coronary artery calcium score greater than 100.A median 29.6 (IQR, 25.0-34.9) years after first registered delivery, 18.9% of women had a history of adverse pregnancy outcomes, with specific pregnancy histories ranging from 1.4% (gestational diabetes) to 9.5% (preterm delivery). The prevalence of any coronary atherosclerosis in women with a history of any adverse pregnancy outcome was 32.1% (95% CI, 30.0%-34.2%), which was significantly higher (prevalence difference, 3.8% [95% CI, 1.6%-6.1%]; prevalence ratio, 1.14 [95% CI, 1.06-1.22]) compared with reference women. History of gestational hypertension and preeclampsia were both significantly associated with higher and similar prevalence of all outcome indexes. For preeclampsia, the highest prevalence difference was observed for any coronary atherosclerosis (prevalence difference, 8.0% [95% CI, 3.7%-12.3%]; prevalence ratio, 1.28 [95% CI, 1.14-1.45]), and the highest prevalence ratio was observed for significant stenosis (prevalence difference, 3.1% [95% CI, 1.1%-5.1%]; prevalence ratio, 2.46 [95% CI, 1.65-3.67]). In adjusted models, odds ratios for preeclampsia ranged from 1.31 (95% CI, 1.07-1.61) for any coronary atherosclerosis to 2.21 (95% CI, 1.42-3.44) for significant stenosis. Similar associations were observed for history of preeclampsia or gestational hypertension among women with low predicted cardiovascular risk.Among Swedish women undergoing coronary computed tomography angiography screening, there was a statistically significant association between history of adverse pregnancy outcomes and image-identified coronary artery disease, including among women estimated to be at low cardiovascular disease risk. Further research is needed to understand the clinical importance of these associations.
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| 9. |
- Thunström, Sofia, et al.
(författare)
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Side differences in the degree of mosaicism of the buccal mucosa in Turner syndrome
- 2019
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Ingår i: Molecular Genetics & Genomic Medicine. - : Wiley. - 2324-9269. ; 7:10
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Tidskriftsartikel (refereegranskat)abstract
- Background The aim was to investigate if there were any differences in the degree of mosaicism between the left- and right-hand sides of the buccal mucosa in women with Turner syndrome. Methods Buccal smears were taken on the left- and right-hand sides at the same time for genetic analyses with fluorescence in situ hybridization in women with Turner syndrome, n = 20; 10 with and 10 without mosaicism based on the blood karyotype, and one control. A difference in the degree of mosaicism >= 5% between the sides was considered as an actual difference and Of 20, 10 (50%) had >= 5% difference in the degree of mosaicism between the left- and right-hand sides of the buccal mucosa. The mean difference was 9.1% and the median was 4.5%, range 1%-38%. The control with ordinary female karyotype had no side difference. Conclusion There was an intraorganic mosaicism of the buccal mucosa with a side difference in the degree of mosaicism of up to 38% in women with Turner syndrome. When mosaicism is strongly suspected, but not confirmed by the blood karyotype, it is recommended that buccal smears from both sides of the oral cavity should be analyzed.
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