| 21. |
- Thrift, Aaron P, et al.
(författare)
-
Obesity and risk of esophageal adenocarcinoma and Barrett's esophagus : a Mendelian randomization study.
- 2014
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 106:11
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Data from observational studies suggest that body mass index (BMI) is causally related to esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE). However, the relationships may be affected by bias and confounding.METHODS: We used data from the Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study: 999 patients with EAC, 2061 patients with BE, and 2169 population controls. We applied the two-stage control function instrumental variable method of the Mendelian randomization approach to estimate the unbiased, unconfounded effect of BMI on risk of EAC and BE. This was performed using a genetic risk score, derived from 29 genetic variants shown to be associated with BMI, as an instrument for lifetime BMI. A higher score indicates propensity to obesity. All tests were two-sided.RESULTS: The genetic risk score was not associated with potential confounders, including gastroesophageal reflux symptoms and smoking. In the instrumental variable analyses (IV), EAC risk increased by 16% (IV-odds ratio [OR] = 1.16, 95% confidence interval [CI] = 1.01 to 1.33) and BE risk increased by 12% (IV-OR = 1.12, 95% CI = 1.00 to 1.25) per 1kg/m(2) increase in BMI. BMI was statistically significantly associated with EAC and BE in conventional epidemiologic analyses.CONCLUSIONS: People with a high genetic propensity to obesity have higher risks of esophageal metaplasia and neoplasia than people with low genetic propensity. These analyses provide the strongest evidence to date that obesity is independently associated with BE and EAC, and is not due to confounding or bias inherent in conventional epidemiologic analyses.
|
|
| 22. |
- Turro, Ernest, et al.
(författare)
-
Whole-genome sequencing of patients with rare diseases in a national health system.
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 583:7814, s. 96-102
-
Tidskriftsartikel (refereegranskat)abstract
- Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered1. Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome. We generated WGS data for 13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to 1,138 of the 7,065 extensively phenotyped participants. We identified 95 Mendelian associations between genes and rare diseases, of which 11 have been discovered since 2015 and at least 79 are confirmed to be aetiological. By generating WGS data of UK Biobank participants2, we found that rare alleles can explain the presence of some individuals in the tails of a quantitative trait for red blood cells. Finally, we identified four novel non-coding variants that cause disease through the disruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates a synergy by using WGS for diagnosis and aetiological discovery in routine healthcare.
|
|
| 23. |
|
|
| 24. |
- Aad, G, et al.
(författare)
-
- 2015
-
swepub:Mat__t
|
|
| 25. |
|
|
| 26. |
- Cao, Christopher, et al.
(författare)
-
Prospective Registry On Mesothelioma Peritonei Treatment (PROMPT) : study design and rationale
- 2012
-
Ingår i: Tumori (Milano). - 0300-8916 .- 2038-2529. ; 98:1, s. 166-171
-
Tidskriftsartikel (refereegranskat)abstract
- Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive and rare form of cancer arising from the mesothelial lining of the peritoneum. Due to the latency period between asbestos exposure and disease progression, the peak in incidence of DMPM is likely to occur in the coming decade for many industrialized nations, with a multitude of industrial, medico-legal and health-related implications(1,2). Traditional therapeutic modalities such as systemic chemotherapy and radiotherapy have not been proven to be effective in the treatment of DMPM, and patients diagnosed with the disease have a life expectancy of less than 12 months(3-5). Combined treatment involving cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been utilized in several specialized centers around the world and has been found to be a feasible procedure with encouraging survival outcomes(6-8).
|
|
| 27. |
-
Collaboration and Resistance during the Holocaust : Belarus, Estonia, Latvia, Lithuania
- 2004
-
Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- This book assembles contributions from the conference "Focus Reichskommissariat Ostland - Collaboration and Resistance during the Holocaust", which took place in Stockholm and Uppsala in April 2002. It presents new perspectives based on new archival sources and oral historiography of the Holocaust during the German occupation of the Baltic countries and part of Belarus: the Reichskommissariat Ostland. Acclaimed historians and new researchers from Belarus, Estonia, Germany, Israel, Latvia, Lithuania, Sweden and the USA focus on the issues of collaboration with or resistance to the Nazis and their extermination policy. The studies of collaboration concern that of the German civilian administration as well as the native local «self-defence» administration in the occupied countries, particularly in Latvia and Lithuania. Several studies deal with resistance in the ghettos, especially Minsk ghetto, and among the partisans in the forests of Belarus and Lithuania. This book has distinctive relevance in bringing together a large amount of archival research done during the period since the fall of the Soviet Union.
|
|
| 28. |
- de Ridder, Lissy, et al.
(författare)
-
Malignancy and Mortality in Pediatric Patients with Inflammatory Bowel Disease : A Multinational Study from the Porto Pediatric IBD Group
- 2014
-
Ingår i: Inflammatory Bowel Diseases. - 1078-0998 .- 1536-4844. ; 20:2, s. 291-300
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The combination of the severity of pediatric-onset inflammatory bowel disease (IBD) phenotypes and the need for intense medical treatment may increase the risk of malignancy and mortality, but evidence regarding the extent of the problem is scarce. Therefore, the Porto Pediatric IBD working group of ESPGHAN conducted a multinational-based survey of cancer and mortality in pediatric IBD. Methods: A survey among pediatric gastroenterologists of 20 European countries and Israel on cancer and/or mortality in the pediatric patient population with IBD was undertaken. One representative from each country repeatedly contacted all pediatric gastroenterologists from each country for reporting retrospectively cancer and/or mortality of pediatric patients with IBD after IBD onset, during 2006-2011. Results: We identified 18 cases of cancers and/or 31 deaths in 44 children (26 males) who were diagnosed with IBD (ulcerative colitis, n = 21) at a median age of 10.0 years (inter quartile range, 3.0-14.0). Causes of mortality were infectious (n = 14), cancer (n = 5), uncontrolled disease activity of IBD (n = 4), procedure-related (n = 3), other non-IBD related diseases (n = 3), and unknown (n = 2). The most common malignancies were hematopoietic tumors (n = 11), of which 3 were hepatosplenic T-cell lymphoma and 3 Ebstein-Barr virus-associated lymphomas. Conclusions: Cancer and mortality in pediatric IBD are rare, but cumulative rates are not insignificant. Mortality is primarily related to infections, particularly in patients with 2 or more immunosuppressive agents, followed by cancer and uncontrolled disease. At least 6 lymphomas were likely treatment-associated by virtue of their phenotype.
|
|
| 29. |
- DHaens, Geert, et al.
(författare)
-
Neuroimmune Modulation Through Vagus Nerve Stimulation Reduces Inflammatory Activity in Crohns Disease Patients: A Prospective Open-label Study
- 2023
-
Ingår i: Journal of Crohn's & Colitis. - : OXFORD UNIV PRESS. - 1873-9946 .- 1876-4479. ; 17:12, s. 1897-1909
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Aims Crohns disease [CD] is a debilitating, inflammatory condition affecting the gastrointestinal tract. There is no cure and sustained clinical and endoscopic remission is achieved by fewer than half of patients with current therapies. The immunoregulatory function of the vagus nerve, the inflammatory reflex, has been established in patients with rheumatoid arthritis and biologic-naive CD. The aim of this study was to explore the safety and efficacy of vagus nerve stimulation in patients with treatment-refractory CD, in a 16-week, open-label, multicentre, clinical trial.Methods A vagus nerve stimulator was implanted in 17 biologic drug-refractory patients with moderately to severely active CD. One patient exited the study pre-treatment, and 16 patients were treated with vagus nerve stimulation [4/16 receiving concomitant biologics] during 16 weeks of induction and 24 months of maintenance treatment. Endpoints included clinical improvement, patient-reported outcomes, objective measures of inflammation [endoscopic/molecular], and safety.Results There was a statistically significant and clinically meaningful decrease in CD Activity Index at Week 16 [mean +/- SD: -86.2 +/- 92.8, p = 0.003], a significant decrease in faecal calprotectin [-2923 +/- 4104, p = 0.015], a decrease in mucosal inflammation in 11/15 patients with paired endoscopies [-2.1 +/- 1.7, p = 0.23], and a decrease in serum tumour necrosis factor and interferon-gamma [46-52%]. Two quality-of-life indices improved in 7/11 patients treated without biologics. There was one study-related severe adverse event: a postoperative infection requiring device explantation.Conclusions Neuroimmune modulation via vagus nerve stimulation was generally safe and well tolerated, with a clinically meaningful reduction in clinical disease activity associated with endoscopic improvement, reduced levels of faecal calprotectin and serum cytokines, and improved quality of life. Graphical Abstract
|
|
| 30. |
- Gaunt, David, et al.
(författare)
-
Introduction
- 2004
-
Ingår i: Collaboration and resistance during the Holocaust. - Bern : Peter Lang. - 3039102451 ; , s. 9-32
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)
|
|
