| 1. |
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| 2. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 3. |
- Drake, TM, et al.
(författare)
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Surgical site infection after gastrointestinal surgery in children: an international, multicentre, prospective cohort study
- 2020
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.MethodsA multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).ResultsOf 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.ConclusionThe odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Rheinbay, E, et al.
(författare)
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Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 102-
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of drivers of cancer has traditionally focused on protein-coding genes1–4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5′ region of TP53, in the 3′ untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.
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| 9. |
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| 10. |
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| 11. |
- Barnes, DR, et al.
(författare)
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Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores
- 2022
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 114:1, s. 109-122
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRecent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers.Methods483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)–negative (PRSER-), or ER-positive (PRSER+) breast cancer risk.ResultsPRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions.ConclusionsPopulation-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.
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| 12. |
- Coignard, J, et al.
(författare)
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A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 1078-
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.
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| 13. |
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| 14. |
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| 15. |
- Dareng, EO, et al.
(författare)
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Polygenic risk modeling for prediction of epithelial ovarian cancer risk
- 2022
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Ingår i: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 30:3, s. 349-362
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, “select and shrink for summary statistics” (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28–1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08–1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21–1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29–1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35–1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
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| 16. |
- Rodriguez-Martin, B, et al.
(författare)
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Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition
- 2020
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 52:3, s. 306-
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Tidskriftsartikel (refereegranskat)abstract
- About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage–fusion–bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of 22 L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors.
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| 17. |
- Akdemir, KC, et al.
(författare)
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Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer
- 2020
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 52:3, s. 294-
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Tidskriftsartikel (refereegranskat)abstract
- Chromatin is folded into successive layers to organize linear DNA. Genes within the same topologically associating domains (TADs) demonstrate similar expression and histone-modification profiles, and boundaries separating different domains have important roles in reinforcing the stability of these features. Indeed, domain disruptions in human cancers can lead to misregulation of gene expression. However, the frequency of domain disruptions in human cancers remains unclear. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumor types, we analyzed 288,457 somatic structural variations (SVs) to understand the distributions and effects of SVs across TADs. Notably, SVs can lead to the fusion of discrete TADs, and complex rearrangements markedly change chromatin folding maps in the cancer genomes. Notably, only 14% of the boundary deletions resulted in a change in expression in nearby genes of more than twofold.
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| 18. |
- Carlevaro-Fita, J, et al.
(författare)
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Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis
- 2020
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1, s. 56-
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Tidskriftsartikel (refereegranskat)abstract
- Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis.
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| 19. |
- Cortes-Ciriano, I, et al.
(författare)
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Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing
- 2020
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 52:3, s. 331-
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Tidskriftsartikel (refereegranskat)abstract
- Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer.
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| 20. |
- Li, YL, et al.
(författare)
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Patterns of somatic structural variation in human cancer genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 112-
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Tidskriftsartikel (refereegranskat)abstract
- A key mutational process in cancer is structural variation, in which rearrangements delete, amplify or reorder genomic segments that range in size from kilobases to whole chromosomes1–7. Here we develop methods to group, classify and describe somatic structural variants, using data from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumour types8. Sixteen signatures of structural variation emerged. Deletions have a multimodal size distribution, assort unevenly across tumour types and patients, are enriched in late-replicating regions and correlate with inversions. Tandem duplications also have a multimodal size distribution, but are enriched in early-replicating regions—as are unbalanced translocations. Replication-based mechanisms of rearrangement generate varied chromosomal structures with low-level copy-number gains and frequent inverted rearrangements. One prominent structure consists of 2–7 templates copied from distinct regions of the genome strung together within one locus. Such cycles of templated insertions correlate with tandem duplications, and—in liver cancer—frequently activate the telomerase gene TERT. A wide variety of rearrangement processes are active in cancer, which generate complex configurations of the genome upon which selection can act.
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| 21. |
- Gerstung, M, et al.
(författare)
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The evolutionary history of 2,658 cancers
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 122-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)4, we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection.
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| 22. |
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| 23. |
- Stenström, P, et al.
(författare)
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Total colonic aganglionosis: multicentre study of surgical treatment and patient-reported outcomes up to adulthood.
- 2020
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Ingår i: BJS open. - 2474-9842. ; 4:5, s. 943-953
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Tidskriftsartikel (refereegranskat)abstract
- Surgery for total colonic aganglionosis (TCA) is designed to preserve continence and achieve satisfactory quality of life. This study evaluated a comprehensive group of clinical and social outcomes.An international multicentre study from eight Nordic hospitals involving examination of case records and a patient-reported questionnaire survey of all patients born with TCA between 1987 and 2006 was undertaken.Of a total of 116 patients, five (4·3 per cent) had died and 102 were traced. Over a median follow-up of 12 (range 0·3-33) years, bowel continuity was established in 75 (73·5 per cent) at a median age of 11 (0·5-156) months. Mucosectomy with a short muscular cuff and straight ileoanal anastomosis (SIAA) (29 patients) or with a J pouch (JIAA) (26) were the most common reconstructions (55 of 72, 76 per cent). Major early postoperative complications requiring surgical intervention were observed in four (6 per cent) of the 72 patients. In 57 children aged over 4 years, long-term functional bowel symptoms after reconstruction included difficulties in holding back defaecation in 22 (39 per cent), more than one faecal accident per week in nine (16 per cent), increased frequency of defaecation in 51 (89 per cent), and social restrictions due to bowel symptoms in 35 (61 per cent). Enterocolitis occurred in 35 (47 per cent) of 72 patients. Supplementary enteral and/or parenteral nutrition was required by 51 (55 per cent) of 93 patients at any time during follow-up. Of 56 responders aged 2-20 years, true low BMI for age was found in 20 (36 per cent) and 13 (23 per cent) were short for age.Reconstruction for TCA was associated with persistent bowel symptoms, and enterocolitis remained common. Multidisciplinary follow-up, including continuity of care in adulthood, might improve care standards in patients with TCA.
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| 24. |
- Yakneen, S, et al.
(författare)
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Butler enables rapid cloud-based analysis of thousands of human genomes
- 2020
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Ingår i: Nature biotechnology. - : Springer Science and Business Media LLC. - 1546-1696 .- 1087-0156. ; 38:3, s. 288-
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Tidskriftsartikel (refereegranskat)abstract
- We present Butler, a computational tool that facilitates large-scale genomic analyses on public and academic clouds. Butler includes innovative anomaly detection and self-healing functions that improve the efficiency of data processing and analysis by 43% compared with current approaches. Butler enabled processing of a 725-terabyte cancer genome dataset from the Pan-Cancer Analysis of Whole Genomes (PCAWG) project in a time-efficient and uniform manner.
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| 25. |
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| 26. |
- Nilsson, K., et al.
(författare)
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Oncological outcomes of standard versus prolonged time to surgery after neoadjuvant chemoradiotherapy for oesophageal cancer in the multicentre, randomised, controlled NeoRes II trial
- 2023
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Ingår i: Annals of Oncology. - : Elsevier. - 0923-7534 .- 1569-8041. ; 34:11, s. 1015-1024
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Tidskriftsartikel (refereegranskat)abstract
- Background: The optimal time to surgery (TTS) after neoadjuvant chemoradiotherapy (nCRT) for oesophageal cancer is unknown and has traditionally been 4-6 weeks in clinical practice. Observational studies have suggested better outcomes, especially in terms of histological response, after prolonged delay of up to 3 months after nCRT. The NeoRes II trial is the first randomised trial to compare standard to prolonged TTS after nCRT for oesophageal cancer.Patients and methods: Patients with resectable, locally advanced oesophageal cancer were randomly assigned to standard delay of surgery of 4-6 weeks or prolonged delay of 10-12 weeks after nCRT. The primary endpoint was complete histological response of the primary tumour in patients with adenocarcinoma (AC). Secondary endpoints included histological tumour response, resection margins, overall and progression-free survival in all patients and stratified by histologic type.Results: Between February 2015 and March 2019, 249 patients from 10 participating centres in Sweden, Norway and Germany were randomised: 125 to standard and 124 to prolonged TTS. There was no significant difference in complete histological response between AC patients allocated to standard (21%) compared to prolonged (26%) TTS (P = 0.429). Tumour regression, resection margins and number of resected lymph nodes, total and metastatic, did not differ between the allocated interventions. The first quartile overall survival in patients allocated to standard TTS was 26.5 months compared to 14.2 months after prolonged TTS (P = 0.003) and the overall risk of death during follow-up was 35% higher after prolonged delay (hazard ratio 1.35, 95% confidence interval 0.94-1.95, P = 0.107).Conclusion: Prolonged TTS did not improve histological complete response or other pathological endpoints, while there was a strong trend towards worse survival, suggesting caution in routinely delaying surgery for >6 weeks after nCRT.
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| 27. |
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| 28. |
- Petersson, M., et al.
(författare)
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Natural history and surgical outcome of Rathke's cleft cysts-A study from the Swedish Pituitary Registry
- 2022
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 96:1, s. 54-61
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Tidskriftsartikel (refereegranskat)abstract
- Objective Rathke's cleft cysts are benign, embryological remnants in the pituitary gland. The majority of them are small and asymptomatic but a few may become large, and cause mass effects, pituitary hormone deficiencies and visual impairment. Recommendations for the follow-up of Rathke's cleft cysts vary since data on the natural history are sparse. Patients and Design Data at diagnosis and at 1, 5 and 10 years for patients with a Rathke's cleft cyst (434 at diagnosis, 317 females) were retrieved from the Swedish Pituitary Registry. Cysts <= 3 mm in diameter were excluded from the study. Measurements Data included demographics, cyst size, pituitary function, visual defects and surgery. Results The mean age at diagnosis was 45 years. In patients with cysts <10 mm in diameter (n = 204) 2.9% had pituitary hormone deficiencies and 2% had visual field impairments. Cyst size did not progress during the 5 years. Cysts with a diameter of >= 10 mm that were not operated (n = 174) decreased in size over the years (p < .01). Pituitary hormone deficiencies and visual impairments were more frequent (18% and 5.7%, respectively) but were stable over time. Transphenoidal surgery was performed in 56 patients of whom 51 underwent surgery before the 1-year follow-up. The mean cyst diameter at diagnosis was 18 mm (range: 930 mm), 36% had pituitary hormone deficiency, 45% had visual field defects and 20% had impaired visual acuity. One year after surgery 60% had no cyst remnants, 50% had a pituitary deficiency, 26% had visual field defects and 12% had impaired visual acuity. No major changes were observed after 5 years. Twelve of the operated patients had a follow-up at 10 years, in eight the cyst remnants or recurrences increased in size over time (p < .05). Conclusions Rathke's cleft cysts with a size less than 10 mm rarely grow and our results indicate that radiological follow-up can be restricted to 5 years. In contrast, progression of postoperative remnants or recurrent cysts is more likely and require long-term follow-up.
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| 29. |
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| 30. |
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| 31. |
- Tangen, A, et al.
(författare)
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Associations Between Cognition and Serotonin 1B Receptor Availability in Healthy Volunteers: A [11C]AZ10419369 Positron Emission Tomography Study
- 2023
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Ingår i: The international journal of neuropsychopharmacology. - : Oxford University Press (OUP). - 1469-5111 .- 1461-1457. ; 26:4, s. 241-248
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe serotonin system has been implicated in several psychiatric disorders. All major psychiatric disorders are associated with cognitive impairment, but treatment improving cognitive deficits is lacking, partly due to limited understanding of the neurobiology of cognitive functioning. Several markers for the serotonin system have been associated with cognitive functions. Our research group previously has reported a positive correlation between serotonin (5-HT1B) receptor availability in the dorsal brainstem and visuospatial memory in a pilot study of healthy individuals. Here, we aim to replicate our previous finding in a larger group of healthy volunteers as well as to investigate putative associations between 5-HT1B receptor availability and other cognitive domains.MethodsForty-three healthy individuals were examined with positron emission tomography using the 5-HT1B receptor radioligand [11C]AZ10419369 and a visuospatial memory test to replicate our previous finding as well as tests of verbal fluency, cognitive flexibility, reaction time, and planning ability to explore other domains potentially associated with the serotonin system.ResultsReplication analysis revealed no statistically significant association between 5-HT1B receptor availability in the dorsal brainstem and visuospatial memory performance. Exploratory analyses showed age-adjusted correlations between 5-HT1B receptor availability in whole brain gray matter and specific brain regions, and number of commission errors, reaction time, and planning ability.ConclusionsHigher 5-HT1B receptor availability was associated with more false-positive responses and faster reaction time but lower performance in planning and problem-solving. These results corroborate previous research supporting an important role of the serotonin system in impulsive behavior and planning ability.
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| 32. |
- Andersson, Eva K., Professor, 1971-, et al.
(författare)
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Trajectories of Latent Vulnerability and Distress : Identifying Social and Spatial Fringes of the Swedish Population
- 2023
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Ingår i: Social Indicators Research. - 0303-8300 .- 1573-0921. ; :169, s. 993-1015
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Tidskriftsartikel (refereegranskat)abstract
- It can be argued that a society is never better than how Individuals on its social and spatial fringes are faring. This motivates the purpose of this paper, which is to study how vulnerable groups can be identified, defined and explored in a spatial perspective using latent class analysis (LCA) on the whole Swedish population. We use space to refine meanings of vulnerability in individuals and groups, by contextualizing their vulnerability. This knowledge is fundamental for creating equal living conditions and for promoting the social cohesion needed for socially sustainable societies. Thus, equality and spatial integration are basic ideas in welfare policy but in recent years, the idea of integration has met various challenges with new population groups, rural–urban polarization, and disadvantaged housing areas. Using register data, we here identified life course trajectories associated with vulnerability, applying LCA to the total Swedish population aged 25 to 59 years. We identified latent classes of life courses, and detected and explored some classes with more vulnerability than others. The spatial patterns of vulnerable individuals were analysed using individualized neighbourhoods including the proportion of closest neighbours belonging to a latent class. A second LCA of vulnerable individuals refined the findings into different types of distress; extra distressed life courses were found in the metropolitan areas in Million program areas in urban outskirts, and other distressed life courses were more often found in unattractive (low housing price) rural areas, rural fringes.
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| 33. |
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| 34. |
- Bashkin, O., et al.
(författare)
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The future public health workforce in a changing world : A conceptual framework for a european–israeli knowledge transfer project
- 2021
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 18:17
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Tidskriftsartikel (refereegranskat)abstract
- Health services quality and sustainability rely mainly on a qualified workforce. Adequately trained public health personnel protect and promote health, avert health disparities, and allow rapid response to health emergencies. Evaluations of the healthcare workforce typically focus on physicians and nurses in curative medical venues. Few have evaluated public health workforce capacity building or sought to identify gaps between the academic training of public health employees and the needs of the healthcare organizations in which they are employed. This project report describes the conceptual framework of “Sharing European Educational Experience in Public Health for Israel (SEEEPHI): harmonization, employability, leadership, and outreach”—a multinational Erasmus+ Capacity Building in Higher Education funded project. By sharing European educational experience and knowledge, the project aims to enhance professionalism and strengthen leadership aspects of the public health workforce in Israel to meet the needs of employers and the country. The project’s work packages, each jointly led by an Israeli and European institution, include field qualification analysis, mapping public health academic training programs, workforce adaptation, and building leadership capacity. In the era of global health changes, it is crucial to assess the capacity building of a well-qualified and competent workforce that enables providing good health services, reaching out to minorities, preventing health inequalities, and confronting emerging health challenges. We anticipate that the methods developed and the lessons learned within the Israeli context will be adaptable and adoptable by other countries through local and cultural adjustments.
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| 35. |
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| 36. |
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| 37. |
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| 38. |
- Bileviciute-Ljungar, I, et al.
(författare)
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Pain Burden in Post-COVID-19 Syndrome following Mild COVID-19 Infection
- 2022
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- The global pandemic of SARS-CoV-2 has affected several hundred million people, and many infected people have suffered from a milder initial infection but have never fully recovered. This observational study investigates the pain burden in sufferers of post-COVID-19 syndrome after a milder initial infection. One hundred post-COVID-19 patients filled out questionnaires regarding sociodemographic data, previous comorbidities, present pharmacological treatment, pain intensity and pain localisation. Health-related quality of life, fatigue, emotional status, and insomnia were measured by validated questionnaires. Multiple post-COVID-19 symptoms, including post-exertional malaise, were evaluated by a symptom questionnaire. Among the 100 participants (mean age 44.5 years), 82% were women, 61% had higher education, and 56% were working full or part time. Nine participants reported previous pain or inflammatory conditions. Among the most painful sites were the head/face, chest, lower extremities, and migrating sites. Generalised pain was self-reported by 75 participants and was estimated in 50 participants. Diagnosis of fibromyalgia according to the 2016 criteria was suspected in 40 participants. Subgroup analyses indicated that comorbidities might play a role in the development of pain. In conclusion, a major part of sufferers from post-COVID-19 syndrome develop pain, and in addition to its many disabling symptoms, there is an urgent need for pain management in post-COVID-19 syndrome.
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| 39. |
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| 40. |
- Bomholt, Tobias, et al.
(författare)
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Hemoglobin A1c and Fructosamine Evaluated in Patients with Type 2 Diabetes Receiving Peritoneal Dialysis Using Long-Term Continuous Glucose Monitoring
- 2022
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Ingår i: Nephron. Clinical practice. - : S. Karger. - 1660-8151 .- 2235-3186. ; 146:2, s. 146-152
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Shortened erythrocyte life span and erythropoietin-stimulating agents may affect hemoglobin A1c (HbA1c) levels in patients receiving peritoneal dialysis (PD). We compared HbA1c with interstitial glucose measured by continuous glucose monitoring (CGM) in patients with type 2 diabetes receiving PD.Methods: Fourteen days of CGM (Ipro2, Medtronic) were performed in 23 patients with type 2 diabetes receiving PD and in 23 controls with type 2 diabetes and an estimated glomerular filtration rate over 60 mL/min/1.73 m2. Patients were matched on gender and age (±5 years). HbA1c (mmol/mol), its derived estimate of mean plasma glucose (eMPGA1c) (mmol/L), and fructosamine (µmol/L) were measured at the end of the CGM period and compared with the mean sensor glucose (mmol/L) from CGM.Results: In the PD group, mean sensor glucose was 0.98 (95% con-fidence interval (CI): 0.43-1.54) mmol/L higher than the eMPGA1c compared with the control group (p = 0.002) where glucose levels were nearly identical (-0.05 (95% CI: -0.35-0.25) mmol/L). A significant association was found between fructosamine and mean sensor glucose using linear regression with no difference between slopes (p = 0.89) or y-intercepts (p = 0.28).Discussion/Conclusion: HbA1c underestimates mean plasma glucose levels in patients with type 2 diabetes receiving PD. However, the clinical significance of this finding is undetermined. Fructosamine seems to more accurately reflect glycemic status. CGM or fructosamine could complement HbA1c to increase the accuracy of glycemic monitoring in the PD population.
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| 41. |
- Borg, Ida, 1981-, et al.
(författare)
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Socio-spatial stratification of housing tenure trajectories in Sweden – a longitudinal cohort study
- 2022
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Ingår i: Advances in Life Course Research. - : Elsevier BV. - 1040-2608. ; 57
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Tidskriftsartikel (refereegranskat)abstract
- Individuals tend to be most mobile when they are between 20 and 40 years of age. This pattern is relatively stable across regions and over time. For geographical mobility, less is known about their transitions between different types of housing and tenure forms. In Sweden, households may select between, principally, three different types of tenure forms, each often coupled with a specific housing type. Households may rent from either public companies (municipality owned) or private landlords in multifamily dwellings, households may own their single-family house privately, or they can cooperatively own a multifamily house as a tenant-owner in an apartment. Yet we lack knowledge of which tenure trajectories individuals tend to follow during their most mobile years, and we also lack knowledge about which factors determine tenure trajectories. Our sample consist of individuals who in 1995 were aged 18–25 and who left their parental house between 1994 and 1995. This study tracks their tenure trajectories for 21 consecutive years starting in 1995 until 2015. The cohorts in our sample were the first who encountered the conditions on the deregulated housing market that are still in place in Sweden today. We followed these cohorts until they were between 39 and 46 years old and used sequence analysis to classify tenure trajectories. One result that stands out is the outstanding and increasing emphasis on home ownership in our sample, quite unlike the traditional picture of the Swedish housing market. Additionally, we found that resources in a broad sense and spatial context have a great impact on the type of trajectory individuals follow.
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| 42. |
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| 43. |
- Champendal, M., et al.
(författare)
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A scoping review of person-centred care strategies used in diagnostic Nuclear Medicine
- 2024
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Ingår i: Radiography. - : Elsevier. - 1078-8174 .- 1532-2831. ; 30:2, s. 448-456
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Forskningsöversikt (refereegranskat)abstract
- IntroductionPerson-centred care (PCC) emphasises the need for the health care professional to prioritise individual patient needs, thereby fostering a collaborative and emphatic environment that empowers patients to actively participate in their own care. This article will explore the purpose of PCC in Nuclear Medicine (NM), while discussing strategies that may be used to implement PCC during diagnostic NM examinations performed on adult patients.MethodsThe scoping review was conducted in accordance with the Joanna Briggs Institute methodology. The search was performed on PubMed, Embase and Cinhal in June 2023 and included studies in English, Spanish, Portuguese and Italian. The research equation combined keywords and Medical Subject Heading terms (MeSH) related to person-centred care (PCC), for all types of nuclear medicine diagnostic examinations performed. Three independent review authors screened all abstracts and titles, and all eligible full-text publications were included in this scoping review.ResultsFifty-three articles, published between 1993 and 2022, met the inclusion criteria for this scoping review. Seven articles were published in 2015 while 56.6 % of all included studies were performed in Europe. Most studies (n = 39/53) focused on the patients only, with the identified patient benefits being: improve patient experience (67.9 %), increase patient comfort (13.2 %), increase patient knowledge (5.7 %), reduction of patient anxiety (9.4 %) and reduction of waiting/scan time (3.8 %).ConclusionThe scoping review identified a lack of research investigating the use of person-centred care strategies in NM. Future research will focus on using an international survey to explore this topic in nuclear medicine departments overseas.Implications for practiceBy applying PCC principles, the NM professional can improve the patient care pathway and increase patient satisfaction, leading to enhanced clinical outcomes.
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| 44. |
- Deane, C. S., et al.
(författare)
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Space omics research in Europe : Contributions, geographical distribution and ESA member state funding schemes
- 2022
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Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 25:3, s. 103920-
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Tidskriftsartikel (refereegranskat)abstract
- The European research community, via European Space Agency (ESA) spaceflight opportunities, has significantly contributed toward our current understanding of spaceflight biology. Recent molecular biology experiments include “omic” analysis, which provides a holistic and systems level understanding of the mechanisms underlying phenotypic adaptation. Despite vast interest in, and the immense quantity of biological information gained from space omics research, the knowledge of ESA-related space omics works as a collective remains poorly defined due to the recent exponential application of omics approaches in space and the limited search capabilities of pre-existing records. Thus, a review of such contributions is necessary to clarify and promote the development of space omics among ESA and ESA state members. To address this gap, in this review, we i) identified and summarized omics works led by European researchers, ii) geographically described these omics works, and iii) highlighted potential caveats in complex funding scenarios among ESA member states.
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| 45. |
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| 46. |
- Eide, A. H., et al.
(författare)
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Barriers for Accessing Assistive Products in Low- and Middle-Income Countries (LMICs)
- 2023
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Ingår i: Studies in Health Technology and Informatics. - : NLM (Medline). - 0926-9630 .- 1879-8365. ; 306, s. 297-302
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Tidskriftsartikel (refereegranskat)abstract
- WHO implemented the Rapid Assistive Technology Assessment in 2021. This is a household survey on self-reported use, need and barriers for accessing AT in 35 countries globally. In order to obtain comparable data, all surveys followed guidelines developed by WHO, including national two-stage random sampling of households. The 2021 rATA survey included 32 of a total of 140 LMICs globally. Around 40 % of the total respondents (all countries) estimated travel distance to be <5 km, varying from less than 10 % to almost 60 % among the countries. Around 15 % had to travel more than 50 km, varying from 1.3 % to 37.5 %. More individuals living in rural as compared to urban areas had to travel more than 25 km to get their main assistive product. Gender differences were marginal. By far the most prevalent barrier to access assistive products was "Cannot afford", amounting to 39.9% and varying from 6.7 % to 79.1 % among countries. This was followed by "No support" with 14.3 %, varying from 2.3 % to 36.9 %, and "Not available" with 8.1 %, varying from 1 % to 21.5 %. More barriers were reported in rural than urban areas and women report more barriers than men. Variation between countries in both travel time and barriers is substantial and country-specific service development is needed to guide service development.
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| 47. |
- Figlioli, G, et al.
(författare)
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The Spectrum of FANCM Protein Truncating Variants in European Breast Cancer Cases
- 2020
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Germline protein truncating variants (PTVs) in the FANCM gene have been associated with a 2–4-fold increased breast cancer risk in case-control studies conducted in different European populations. However, the distribution and the frequency of FANCM PTVs in Europe have never been investigated. In the present study, we collected the data of 114 European female breast cancer cases with FANCM PTVs ascertained in 20 centers from 13 European countries. We identified 27 different FANCM PTVs. The p.Gln1701* PTV is the most common PTV in Northern Europe with a maximum frequency in Finland and a lower relative frequency in Southern Europe. On the contrary, p.Arg1931* seems to be the most common PTV in Southern Europe. We also showed that p.Arg658*, the third most common PTV, is more frequent in Central Europe, and p.Gln498Thrfs*7 is probably a founder variant from Lithuania. Of the 23 rare or unique FANCM PTVs, 15 have not been previously reported. We provide here the initial spectrum of FANCM PTVs in European breast cancer cases.
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| 48. |
- Gonzalez-Franquesa, Alba, et al.
(författare)
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Discovery of thymosin β4 as a human exerkine and growth factor
- 2021
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Ingår i: American Journal of Physiology - Cell Physiology. - : American Physiological Society. - 0363-6143 .- 1522-1563. ; 321:5, s. 770-778
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Tidskriftsartikel (refereegranskat)abstract
- Skeletal muscle is an endocrine organ secreting exercise-induced factors (exerkines), which play a pivotal role in interorgan cross talk. Using mass spectrometry (MS)-based proteomics, we characterized the secretome and identified thymosin b4 (TMSB4X) as the most upregulated secreted protein in the media of contracting C2C12 myotubes. TMSB4X was also acutely increased in the plasma of exercising humans irrespective of the insulin resistance condition or exercise mode. Treatment of mice with TMSB4X did not ameliorate the metabolic disruptions associated with diet induced-obesity, nor did it enhance muscle regeneration in vivo. However, TMSB4X increased osteoblast proliferation and neurite outgrowth, consistent with its WADA classification as a prohibited growth factor. Therefore, we report TMSB4X as a human exerkine with a potential role in cellular cross talk.
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| 49. |
- Hu, Xiao-Lei, et al.
(författare)
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Study protocol for a randomized, controlled, multicentre, pragmatic trial with Rehabkompassen®-a digital structured follow-up tool for facilitating patient-tailored rehabilitation in persons after stroke
- 2023
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Ingår i: Trials. - : BioMed Central (BMC). - 1745-6215. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundStroke is a leading cause of disability among adults worldwide. A timely structured follow-up tool to identify patients' rehabilitation needs and develop patient-tailored rehabilitation regimens to decrease disability is largely lacking in current stroke care. The overall purpose of this study is to evaluate the effectiveness of a novel digital follow-up tool, Rehabkompassen (R), among persons discharged from acute care settings after a stroke.MethodsThis multicentre, parallel, open-label, two-arm pragmatic randomized controlled trial with an allocation ratio of 1:1 will be conducted in Sweden. A total of 1106 adult stroke patients will have follow-up visits in usual care settings at 3 and 12 months after stroke onset. At the 3-month follow-up, participants will have a usual outpatient visit without (control group, n = 553) or with (intervention group, n = 553) the Rehabkompassen (R) tool. All participants will receive the intervention at the 12-month follow-up visit. Feedback from the end-users (patient and health care practitioners) will be collected after the visits. The primary outcomes will be the patients' independence and social participation at the 12-month visits. Secondary outcomes will include end-users' satisfaction, barriers and facilitators for adopting the instrument, other stroke impacts, health-related quality of life and the cost-effectiveness of the instrument, calculated by incremental cost per quality-adjusted life year (QALY).DiscussionThe outcomes of this trial will inform clinical practice and health care policy on the role of the Rehabkompassen (R) digital follow-up tool in the post-acute continuum of care after stroke.Trial registrationClinicalTrials.gov NCT04915027. Registered on 4 June 2021. ISRCTN registry ISRCTN63166587. Registered on 21 August 2023.
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