| 1. |
- Carlsson, Jessica, 1984-, et al.
(författare)
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Quantity and quality of nucleic acids extracted from archival formalin fixed paraffin embedded prostate biopsies
- 2018
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Ingår i: BMC Medical Research Methodology. - : BioMed Central. - 1471-2288. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In Sweden, human tissue samples obtained from diagnostic and surgical procedures have for decades been routinely stored in a formalin-fixed, paraffin-embedded, form. Through linkage with nationwide registers, these samples are available for molecular studies to identify biomarkers predicting mortality even in slow-progressing prostate cancer. However, tissue fixation causes modifications of nucleic acids, making it challenging to extract high-quality nucleic acids from formalin fixated tissues.METHODS: In this study, the efficiency of five commercial nucleic acid extraction kits was compared on 30 prostate biopsies with normal histology, and the quantity and quality of the products were compared using spectrophotometry and Agilent's BioAnalyzer. Student's t-test's and Bland-Altman analyses were performed in order to investigate differences in nucleic acid quantity and quality between the five kits. The best performing extraction kits were subsequently tested on an additional 84 prostate tumor tissues. A Spearman's correlation test and linear regression analyses were performed in order to investigate the impact of tissue age and amount of tissue on nucleic acid quantity and quality.RESULTS: Nucleic acids extracted with RNeasy® FFPE and QIAamp® DNA FFPE Tissue kit had the highest quantity and quality, and was used for extraction from 84 tumor tissues. Nucleic acids were successfully extracted from all biopsies, and the amount of tumor (in millimeter) was found to have the strongest association with quantity and quality of nucleic acids.CONCLUSIONS: To conclude, this study shows that the choice of nucleic acid extraction kit affects the quantity and quality of extracted products. Furthermore, we show that extraction of nucleic acids from archival formalin-fixed prostate biopsies is possible, allowing molecular studies to be performed on this valuable sample collection.
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| 2. |
- Ludvigsson, Jonas F., et al.
(författare)
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Influenza H1N1 vaccination and adverse pregnancy outcome
- 2013
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 28:7, s. 579-588
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Tidskriftsartikel (refereegranskat)abstract
- Although vaccines against influenza can reduce maternal morbidity and mortality, large-scale data on adverse effects in the offspring are scarce. Historical cohort study in Stockholm County, Sweden. We linked H1N1 vaccination data (Pandemrix(A (R)), a mono-valent AS03 adjuvanted H1N1 vaccine) with pregnancy and birth data from 21,087 women with singleton offspring conceived between February 2009 and January 2010 (vaccinated during pregnancy: n = 13,297 vs. unvaccinated: n = 7,790). Data were analysed by conceptualizing the observational cohort as a series of nested cohorts defined at each week of gestation. Logistic regression estimated odds ratios (ORs) for low birth weight (LBW, < 2,500 g), preterm birth (< 37 completed weeks), small-for-gestational age (SGA, < 10th percentile of the gestational age-specific birth weight within the cohort), low 5-min Apgar score (< 7), and caesarean section. Data were adjusted for potential confounders, including maternal age, body mass index, smoking, parity, civil status and comorbidities. Compared with infants of non-vaccinated women, infants of vaccinated women had similar adjusted ORs (95 % CI) for LBW (0.91; 0.79-1.04), preterm birth (0.99; 0.89-1.10), SGA (0.97; 0.90-1.05), low Apgar score (1.05, 0.84-1.31), and a marginal risk reduction for caesarean section (0.94, 0.89-0.99). H1N1 vaccination during pregnancy, using an AS03-adjuvanted vaccine, does not appear to adversely influence offspring risks of LBW, preterm birth, SGA, or low Apgar score. Our results suggest that this vaccine is safe for the offspring when used in different stages of pregnancy.
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| 3. |
- Zelic, Renata, et al.
(författare)
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Estimation of Relative and Absolute Risks in a Competing-Risks Setting Using a Nested Case-Control Study Design : Example From the ProMort Study
- 2019
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Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1165-1173
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we describe the Prognostic Factors for Mortality in Prostate Cancer (ProMort) study and use it to demonstrate how the weighted likelihood method can be used in nested case-control studies to estimate both relative and absolute risks in the competing-risks setting. ProMort is a case-control study nested within the National Prostate Cancer Register (NPCR) of Sweden, comprising 1,710 men diagnosed with low- or intermediate-risk prostate cancer between 1998 and 2011 who died from prostate cancer (cases) and 1,710 matched controls. Cause-specific hazard ratios and cumulative incidence functions (CIFs) for prostate cancer death were estimated in ProMort using weighted flexible parametric models and compared with the corresponding estimates from the NPCR cohort. We further drew 1,500 random nested case-control subsamples of the NPCR cohort and quantified the bias in the hazard ratio and CIF estimates. Finally, we compared the ProMort estimates with those obtained by augmenting competing-risks cases and by augmenting both competing-risks cases and controls. The hazard ratios for prostate cancer death estimated in ProMort were comparable to those in the NPCR. The hazard ratios for dying from other causes were biased, which introduced bias in the CIFs estimated in the competing-risks setting. When augmenting both competing-risks cases and controls, the bias was reduced.
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| 4. |
- Zelic, Renata, et al.
(författare)
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Interchangeability of light and virtual microscopy for histopathological evaluation of prostate cancer
- 2021
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Virtual microscopy (VM) holds promise to reduce subjectivity as well as intra- and inter-observer variability for the histopathological evaluation of prostate cancer. We evaluated (i) the repeatability (intra-observer agreement) and reproducibility (inter-observer agreement) of the 2014 Gleason grading system and other selected features using standard light microscopy (LM) and an internally developed VM system, and (ii) the interchangeability of LM and VM. Two uro-pathologists reviewed 413 cores from 60 Swedish men diagnosed with non-metastatic prostate cancer 1998-2014. Reviewer 1 performed two reviews using both LM and VM. Reviewer 2 performed one review using both methods. The intra- and inter-observer agreement within and between LM and VM were assessed using Cohen's kappa and Bland and Altman's limits of agreement. We found good repeatability and reproducibility for both LM and VM, as well as interchangeability between LM and VM, for primary and secondary Gleason pattern, Gleason Grade Groups, poorly formed glands, cribriform pattern and comedonecrosis but not for the percentage of Gleason pattern 4. Our findings confirm the non-inferiority of VM compared to LM. The repeatability and reproducibility of percentage of Gleason pattern 4 was poor regardless of method used warranting further investigation and improvement before it is used in clinical practice.
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| 5. |
- Zelic, Renata, et al.
(författare)
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Prognostic Utility of the Gleason Grading System Revisions and Histopathological Factors Beyond Gleason Grade.
- 2022
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Ingår i: Clinical Epidemiology. - : Dove Medical Press Ltd.. - 1179-1349 .- 1179-1349. ; 14, s. 59-70
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Tidskriftsartikel (refereegranskat)abstract
- Background: The International Society of Urological Pathology (ISUP) revised the Gleason system in 2005 and 2014. The impact of these changes on prostate cancer (PCa) prognostication remains unclear.Objective: To evaluate if the ISUP 2014 Gleason score (GS) predicts PCa death better than the pre-2005 GS, and if additional histopathological information can further improve PCa death prediction.Patients and Methods: We conducted a case-control study nested among men in the National Prostate Cancer Register of Sweden diagnosed with non-metastatic PCa 1998-2015. We included 369 men who died from PCa (cases) and 369 men who did not (controls). Two uro-pathologists centrally re-reviewed biopsy ISUP 2014 Gleason grading, poorly formed glands, cribriform pattern, comedonecrosis, perineural invasion, intraductal, ductal and mucinous carcinoma, percentage Gleason 4, inflammation, high-grade prostatic intraepithelial neoplasia (HGPIN) and post-atrophic hyperplasia. Pre-2005 GS was back-transformed using i) information on cribriform pattern and/or poorly formed glands and ii) the diagnostic GS from the registry. Models were developed using Firth logistic regression and compared in terms of discrimination (AUC).Results: The ISUP 2014 GS (AUC = 0.808) performed better than the pre-2005 GS when back-transformed using only cribriform pattern (AUC = 0.785) or both cribriform and poorly formed glands (AUC = 0.792), but not when back-transformed using only poorly formed glands (AUC = 0.800). Similarly, the ISUP 2014 GS performed better than the diagnostic GS (AUC = 0.808 vs 0.781). Comedonecrosis (AUC = 0.811), HGPIN (AUC = 0.810) and number of cores with ≥50% cancer (AUC = 0.810) predicted PCa death independently of the ISUP 2014 GS.Conclusion: The Gleason Grading revisions have improved PCa death prediction, likely due to classifying cribriform patterns, rather than poorly formed glands, as Gleason 4. Comedonecrosis, HGPIN and number of cores with ≥50% cancer further improve PCa death discrimination slightly.
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| 6. |
- Zugna, Daniela, et al.
(författare)
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Mortality Rate in Children Born to Mothers and Fathers With Celiac Disease : A Nationwide Cohort Study
- 2013
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Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 177:12, s. 1348-1355
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Tidskriftsartikel (refereegranskat)abstract
- Celiac disease (CD) is associated with increased mortality rate and adverse pregnancy outcome, but little is known about offspring mortality rate. In this nationwide retrospective cohort study, we identified persons whose biopsy-verified CD was diagnosed in Sweden in 19692008. We compared mortality rates in children born to mothers with and without CD (n 16,121 vs. n 61,782) and children born to fathers with and without CD (n 9,289 vs. n 32,984). Median age of offspring at end of follow-up was 28.7 (range, 16.739.7) years. We also examined mortality rates in children born to mothers with undiagnosed CD (later CD diagnosis; n 12,919) and diagnosed CD (n 3,202) to determine if intrauterine exposures associated with CD could affect offspring mortality rate. We estimated hazard ratios for death by using Cox regression. Death rates were independent of maternal CD (60 deaths per 100,000 person-years in children of mothers with CD, vs. 54 in controls) and paternal CD (53 deaths per 100,000 person-years in children of fathers with CD, vs. 53 in controls). Corresponding adjusted hazard ratios were 1.09 (95 confidence interval: 0.95, 1.26) for maternal CD and 1.02 (95 confidence interval: 0.85, 1.23) for paternal CD. Death rates were similar in children born to mothers with undiagnosed CD and in children whose mothers had diagnosed CD during pregnancy. Parental CD does not seem to influence mortality rate in offspring, which suggests that neither genetic influences of CD nor intrauterine conditions have adverse effects on offspring mortality rate.
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| 7. |
- Zugna, Daniela, et al.
(författare)
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Risk of Congenital Malformations Among Offspring of Mothers and Fathers With Celiac Disease : A Nationwide Cohort Study
- 2014
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 12:7, s. 1108-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Many patients with celiac disease experience malabsorption, weight loss, and anemia; undiagnosed celiac disease during pregnancy has been linked with adverse outcomes. Studies of celiac disease and congenital malformations in offspring have been underpowered. We investigated the risk of congenital malformations among the offspring of parents with celiac disease. METHODS: We performed a nationwide cohort study of data from linked health care registers in Sweden from 1973 through 2009. We collected histopathology data from 28 pathology departments in Sweden to identify individuals with celiac disease (based on the presence of villous atrophy). We estimated the risks of malformations in the offspring of mothers and fathers with and without celiac disease. Logistic regression was used to estimate adjusted prevalence odds ratios (aPORs) with 95% confidence intervals (CIs). RESULTS: Among 11,382 offspring of mothers with celiac disease, there were 672 cases (5.9%) of malformation compared with 2098 cases (5.1%) among 40,922 offspring of mothers without celiac disease. Similarly, 352 (5.9%) of 6002 offspring of fathers with celiac disease and 1009 (5.1%) of 19,600 offspring of fathers without celiac disease had a malformation. In adjusted analyses, the offspring of mothers or fathers with celiac disease had a slightly increased risk of having children with malformations (for those with mothers with celiac disease: aPOR, 1.15; 95% CI, 1.05-1.26; for those with fathers with celiac disease: aPOR, 1.14; 95% CI, 1.00-1.29). However, these excess risks decreased or vanished entirely when we restricted our data to births since 2000 (for those with mothers with celiac disease: aPOR, 1.11; and 95% CI, 0.79-1.56; for those with fathers with celiac disease: aPOR, 1.01; 95% CI, 0.81-1.26). CONCLUSIONS: In a nationwide study, we found an increased risk for malformation among the offspring of mothers or fathers with celiac disease. However, the excess risk is small; the upper limits of the CIs for malformation indicate a 29% maximum relative increase.
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