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- Caspers, I. A., et al.
(författare)
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Effect of preoperative chemotherapy on the histopathological classification of gastric cancer
- 2024
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Ingår i: Gastric Cancer. - : Springer. - 1436-3291 .- 1436-3305. ; 27, s. 102-109
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the era of individualized gastric cancer (GC) treatment, accurate determination of histological subtype becomes increasingly relevant. As yet, it is unclear whether preoperative chemotherapy may affect the histological subtype. The aim of this study was to assess concordance in histological subtype between pretreatment biopsies and surgical resection specimens before and after the introduction of perioperative treatment.Methods: Histological subtype was centrally determined in paired GC biopsies and surgical resection specimens of patients treated with either surgery alone (SA) in the Dutch D1/D2 study or with preoperative chemotherapy (CT) in the CRITICS trial. The histological subtype as determined in the resection specimen was considered the gold standard. Concordance rates and sensitivity and specificity of intestinal, diffuse, mixed, and "other" subtypes of GC were analyzed.Results: In total, 105 and 515 pairs of GC biopsies and resection specimens of patients treated in the SA and CT cohorts, respectively, were included. Overall concordance in the histological subtype was 72% in the SA and 74% in the CT cohort and substantially higher in the diffuse subtype (83% and 86%) compared to the intestinal (70% and 74%), mixed (21% and 33%) and "other" subtypes (54% and 54%). In the SA cohort, sensitivities and specificities were 0.88 and 0.71 in the intestinal, 0.67 and 0.93 in the diffuse, 0.20 and 0.98 in the mixed, and 0.50 and 0.93 in the "other" subtypes, respectively.Conclusion: Our results suggest that accurate determination of histological subtype on gastric cancer biopsies is suboptimal but that the impact of preoperative chemotherapy on histological subtype is negligible.
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- Hagenbeek, FA, et al.
(författare)
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Heritability estimates for 361 blood metabolites across 40 genome-wide association studies
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 39-
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Tidskriftsartikel (refereegranskat)abstract
- Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2total), and the proportion of heritability captured by known metabolite loci (h2Metabolite-hits) for 309 lipids and 52 organic acids. Our study reveals significant differences in h2Metabolite-hits among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h2Metabolite-hits estimates than phosphatidylcholines with low degrees of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes.
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| 8. |
- Olsson, G, et al.
(författare)
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Metoprolol-induced reduction in post-infarction mortality : pooled results from five double-blind randomized trials
- 1992
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 13:1, s. 28-32
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Tidskriftsartikel (refereegranskat)abstract
- Several postinfarction trials have evaluated the effect of secondary prophylaxis with different beta-blockers. Although so called meta-analysis of the results from all the trials have shown a beneficial effect of postinfarction beta-blockade, many of the individual studies have shown inconclusive results, mainly due to low statistical power. In order to obtain an evaluation of the merits of postinfarction therapy with metoprolol, data from the five available studies with metoprolol have been pooled into one database. In the total material 5474 patients (4353 men, 1121 women) have been studied during double-blind therapy with metoprolol 100 mg twice daily or matching placebo. The follow-up ranges from 3 months to 3 years. In total 4732 patient years of observation have been obtained. In total there were 223 deaths in the placebo-treated patients as compared to 188 deaths in the metoprolol-treated patients (P = 0.036), which corresponds to mortality rates of 97.0 and 78.3 per 1000 patient years, respectively. The mortality reduction was found both in men and women. As has been reported from individual postinfarction beta-blocker trials, the pooled results showed a marked reduction in sudden deaths (104 in the placebo group, 62 in the metoprolol group, P = 0.002). In a Cox regression model the influence of sex, age and smoking habits on the effect of metoprolol was evaluated. None of these factors influenced the metoprolol effect significantly. It is concluded that metoprolol therapy after acute myocardial infarction reduces the total number of deaths, and especially sudden cardiac deaths. The mortality reduction was independent of gender, age and smoking habits. Available data support a continuous beneficial effect.
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