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- López-Isac, Elena, et al.
(författare)
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Brief Report : IRF4 Newly Identified as a Common Susceptibility Locus for Systemic Sclerosis and Rheumatoid Arthritis in a Cross-Disease Meta-Analysis of Genome-Wide Association Studies
- 2016
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 68:9, s. 2338-2344
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that have similar clinical and immunologic characteristics. To date, several shared SSc–RA genetic loci have been identified independently. The aim of the current study was to systematically search for new common SSc–RA loci through an interdisease meta–genome-wide association (meta-GWAS) strategy. Methods: The study was designed as a meta-analysis combining GWAS data sets of patients with SSc and patients with RA, using a strategy that allowed identification of loci with both same-direction and opposite-direction allelic effects. The top single-nucleotide polymorphisms were followed up in independent SSc and RA case–control cohorts. This allowed an increase in the sample size to a total of 8,830 patients with SSc, 16,870 patients with RA, and 43,393 healthy controls. Results: This cross-disease meta-analysis of the GWAS data sets identified several loci with nominal association signals (P < 5 × 10−6) that also showed evidence of association in the disease-specific GWAS scans. These loci included several genomic regions not previously reported as shared loci, as well as several risk factors that were previously found to be associated with both diseases. Follow-up analyses of the putatively new SSc–RA loci identified IRF4 as a shared risk factor for these 2 diseases (Pcombined = 3.29 × 10−12). Analysis of the biologic relevance of the known SSc–RA shared loci identified the type I interferon and interleukin-12 signaling pathways as the main common etiologic factors. Conclusion: This study identified a novel shared locus, IRF4, for the risk of SSc and RA, and highlighted the usefulness of a cross-disease GWAS meta-analysis strategy in the identification of common risk loci.
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| 2. |
- Beijert, Irene J., et al.
(författare)
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International Opinions on Grading of Urothelial Carcinoma : A Survey Among European Association of Urology and International Society of Urological Pathology Members
- 2023
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Ingår i: European Urology Open Science. - 2666-1691. ; 52, s. 154-165
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Tidskriftsartikel (refereegranskat)abstract
- Background: Grade of non–muscle-invasive bladder cancer (NMIBC) is an important prognostic factor for progression. Currently, two World Health Organization (WHO) classification systems (WHO1973, categories: grade 1–3, and WHO2004 categories: papillary urothelial neoplasm of low malignant potential [PUNLMP], low-grade [LG], high-grade [HG] carcinoma) are used. Objective: To ask the European Association of Urology (EAU) and International Society of Urological Pathology (ISUP) members regarding their current practice and preferences of grading systems. Design, setting, and participants: A web-based, anonymous questionnaire with ten questions on grading of NMIBC was created. The members of EAU and ISUP were invited to complete an online survey by the end of 2021. Thirteen experts had previously answered the same questions. Outcome measurements and statistical analysis: The submitted answers from 214 ISUP members, 191 EAU members, and 13 experts were analyzed. Results and limitations: Currently, 53% use only the WHO2004 system and 40% use both systems. According to most respondents, PUNLMP is a rare diagnosis with management similar to Ta-LG carcinoma. The majority (72%) would consider reverting back to WHO1973 if grading criteria were more detailed. Separate reporting of WHO1973-G3 within WHO2004-HG would influence clinical decisions for Ta and/or T1 tumors according the majority (55%). Most respondents preferred a two-tier (41%) or a three-tier (41%) grading system. The current WHO2004 grading system is supported by a minority (20%), whereas nearly half (48%) supported a hybrid three- or four-tier grading system composed of both WHO1973 and WHO2004. The survey results of the experts were comparable with ISUP and EAU respondents. Conclusions: Both the WHO1973 and the WHO2004 grading system are still widely used. Even though opinions on the future of bladder cancer grading were strongly divided, there was limited support for WHO1973 and WHO2004 in their current formats, while the hybrid (three-tier) grading system with LG, HG-G2, and HG-G3 as categories could be considered the most promising alternative. Patient summary: Grading of non–muscle-invasive bladder cancer (NMIBC) is a matter of ongoing debate and lacks international consensus. We surveyed urologists and pathologists of European Association of Urology and International Society of Urological Pathology on their preferences regarding NMIBC grading to generate a multidisciplinary dialogue. Both the “old” World Health Organization (WHO) 1973 and the “new” WHO2004 grading schemes are still used widely. However, continuation of both the WHO1973 and the WHO2004 system showed limited support, while a hybrid grading system composed of both the WHO1973 and the WHO2004 classification system may be considered a promising alternative.
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| 3. |
- Lopez-Beltran, Antonio, et al.
(författare)
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International Society of Urological Pathology (ISUP) Consensus Conference on Current Issues in Bladder Cancer : Working Group 3: Subcategorization of T1 Bladder Cancer
- 2024
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Ingår i: American Journal of Surgical Pathology. - 0147-5185. ; 48:1, s. 24-31
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Tidskriftsartikel (refereegranskat)abstract
- Emerging data on T1 bladder cancer subcategorization (aka substaging) suggests a correlation with oncological outcomes. The International Society of Urological Pathology (ISUP) organized the 2022 consensus conference in Basel, Switzerland to focus on current issues in bladder cancer and tasked working group 3 to make recommendations for T1 subcategorization in transurethral bladder resections. For this purpose, the ISUP developed and circulated a survey to their membership querying approaches to T1 bladder cancer subcategorization. In particular, clinical relevance, pathological reporting, and endorsement of T1 subcategorization in the daily practice of pathology were surveyed. Of the respondents of the premeeting survey, about 40% do not routinely report T1 subcategory. We reviewed literature on bladder T1 subcategorization, and screened selected articles for clinical performance and practicality of T1 subcategorization methods. Published literature offered evidence of the clinical rationale for T1 subcategorization and at the conference consensus (83% of conference attendants) was obtained to report routinely T1 subcategorization of transurethral resections. Semiquantitative T1 subcategorization was favored (37%) over histoanatomic methods (4%). This is in line with literature findings on practicality and prognostic impact, that is, a shift of publications from histoanatomic to semiquantitative methods or by reports incorporating both methodologies is apparent over the last decade. However, 59% of participants had no preference for either methodology. They would add a comment in the report briefly stating applied method, interpretation criteria (including cutoff), and potential limitations. When queried on the terminology of T1 subcategorization, 34% and 20% of participants were in favor of T1 (microinvasive) versus T1 (extensive) or T1 (focal) versus T1 (nonfocal), respectively.
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| 4. |
- van der Kwast, Theo, et al.
(författare)
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International Society of Urological Pathology Expert Opinion on Grading of Urothelial Carcinoma
- 2022
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Ingår i: European Urology Focus. - : Elsevier BV. - 2405-4569. ; 8:2, s. 438-446
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Forskningsöversikt (refereegranskat)abstract
- Context: Grading is the mainstay for treatment decisions for patients with non–muscle-invasive bladder cancer (NMIBC). Objective: To determine the requirements for an optimal grading system for NMIBC via expert opinion. Evidence acquisition: A multidisciplinary working group established by the International Society of Urological Pathology reviewed available clinical, histopathological, and molecular evidence for an optimal grading system for bladder cancer. Evidence synthesis: Bladder cancer grading is a continuum and five different grading systems based on historical grounds could be envisaged. Splitting of the World Health Organization (WHO) 2004 low-grade class for NMIBC lacks diagnostic reproducibility and molecular-genetic support, while showing little difference in progression rate. Subdividing the clinically heterogeneous WHO 2004 high-grade class for NMIBC into intermediate and high risk categories using the WHO 1973 grading is supported by both clinical and molecular-genetic findings. Grading criteria for the WHO 1973 scheme were detailed on the basis of literature findings and expert opinion. Conclusions: Splitting of the WHO 2004 high-grade category into WHO 1973 grade 2 and 3 subsets is recommended. Provision of more detailed histological criteria for the WHO 1973 grading might facilitate the general acceptance of a hybrid four-tiered grading system or—as a preferred option—a more reproducible three-tiered system distinguishing low-, intermediate (high)-, and high-grade NMIBC. Patient summary: Improvement of the current systems for grading bladder cancer may result in better informed treatment decisions for patients with bladder cancer. A three-tiered grading system for non–muscle invasive bladder cancer derived by splitting the heterogeneous World Health Organization (WHO) 2004 high-grade category into WHO 1973 grade 2 and 3 subsets is recommended, as this may result in more informed treatment decisions.
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