| 1. |
- Olafsson, S, et al.
(författare)
-
Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations
- 2017
-
Ingår i: NPJ genomic medicine. - : Springer Science and Business Media LLC. - 2056-7944. ; 2, s. 24-
-
Tidskriftsartikel (refereegranskat)abstract
- A meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 × 10−7, 4.3 × 10−9) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.
|
|
| 2. |
- Valdes-Marquez, E., et al.
(författare)
-
Relative effects of LDL-C on ischemic stroke and coronary disease A Mendelian randomization study
- 2019
-
Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 92:11
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To examine the causal relevance of lifelong differences in low-density lipoprotein cholesterol (LDL-C) for ischemic stroke (IS) relative to that for coronary heart disease (CHD) using a Mendelian randomization approach. We undertook a 2-sample Mendelian randomization, based on summary data, to estimate the causal relevance of LDL-C for risk of IS and CHD. Information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels was used to estimate the causal effects of LDL-C for IS and IS subtypes (based on 12,389 IS cases from METASTROKE) and for CHD (based on 60,801 cases from CARDIoGRAMplusC4D). We then assessed the effects of LDL-C on IS and CHD for heterogeneity. A 1 mmol/L higher genetically determined LDL-C was associated with a 50% higher risk of CHD (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.32-1.68, p = 1.1 x 10(-8)). By contrast, the causal effect of LDL-C was much weaker for IS (OR 1.12, 95% CI 0.96-1.30, p = 0.14; p for heterogeneity = 2.6 x 10(-3)) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84-1.33, p = 0.64; p for heterogeneity = 8.6 x 10(-3)) when compared with that for CHD. In contrast with the consistent effects of LDL-C-lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of etiologically distinct IS subtypes may contribute to the differences observed.
|
|
| 3. |
|
|
| 4. |
- Sturesson, Christian, et al.
(författare)
-
Liver-first strategy for synchronous colorectal liver metastases : an intention-to-treat analysis
- 2017
-
Ingår i: HPB. - : Elsevier BV. - 1365-182X. ; 19:1, s. 52-58
-
Tidskriftsartikel (refereegranskat)abstract
- Background The liver-first strategy signifies resection of liver metastases before the primary colorectal cancer. The aim of the present study was to compare failure to complete intended treatment and survival in liver-first and classical strategies. Methods All patients with colorectal cancer and synchronous liver metastases planned for sequential radical surgery in a single institution between 2011 and 2015 were included. Results A total of 109 patients were presented to a multidisciplinary team conference (MDT) with un-resected colorectal cancer and synchronous liver metastases. Seventy-five patients were planned as liver-first, whereas 34 were recommended the classical strategy. Twenty-six patients (35%) failed to complete treatment in the liver-first group compared to 10 patients in the classical group (P = 0.664). Reason for failure was most commonly disease progression. A total of 91 patients had the primary tumor resected before the liver metastases of which 67 before referral and 24 after allocation at MDT. Median survival after diagnosis in this group was 60 (48–73) months compared to 46 (31–60) months in the group operated with liver-first strategy (n = 49), (P = 0.310). Discussion Up to 35% of patients with colorectal cancer and synchronous liver metastases do not complete the intended treatment of liver and bowel resections, irrespective of treatment strategy.
|
|
| 5. |
- Valdimarsson, Valentinus T., et al.
(författare)
-
Outcomes of liver-first strategy and classical strategy for synchronous colorectal liver metastases in Sweden
- 2018
-
Ingår i: HPB. - : Elsevier BV. - 1365-182X .- 1477-2574. ; 20:5, s. 441-447
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with synchronous colorectal liver metastases (sCRLM) are increasingly operated with liver resection before resection of the primary cancer. The aim of this study was to compare outcomes in patients following the liver-first strategy and the classical strategy (resection of the bowel first) using prospectively registered data from two nationwide registries. Methods: Clinical, pathological and survival outcomes were compared between the liver-first strategy and the classical strategy (2008-2015). Overall survival was calculated. Results: A total of 623 patients were identified, of which 246 were treated with the liver-first strategy and 377 with the classical strategy. The median follow-up was 40 months. Patients chosen for the classical strategy more often had T4 primary tumours (23% vs 14%, P = 0.012) and node-positive primaries (70 vs 61%, P = 0.015). The liver-first patients had a higher liver tumour burden score (4.1 (2.5-6.3) vs 3.6 (2.2-5.1), P = 0.003). No difference was seen in five-year overall survival between the groups (54% vs 49%, P = 0.344). A majority (59%) of patients with rectal cancer were treated with the liver-first strategy. Conclusion: The liver-first strategy is currently the dominant strategy for sCRLM in patients with rectal cancer in Sweden. No difference in overall survival was noted between strategies.
|
|
| 6. |
- Valdimarsson, Valentinus T., et al.
(författare)
-
Repeat procedures for recurrent colorectal liver metastases : Analysis of long-term liver regeneration and outcome
- 2019
-
Ingår i: Cancer Management and Research. - 1179-1322. ; 11, s. 2617-2622
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aim: Repeat hepatectomy is increasingly performed for the management of recurrent colorectal liver metastases (CRLM). The aim of this study was to evaluate longterm functional liver volume (FLV) after a second hepatic procedure and to measure survival outcome. Methods: In this retrospective cohort study, patients treated for recurrent CRLM in the years 2005-2015 at two liver centers were included. Total FLV was calculated before the first procedure and before and after the second procedure. Overall survival was calculated. Results: Eighty-two patients were identified. The median follow-up was 53 (40-71) months from the first procedure. The median interval between first and second procedure was 13 (8-22) months. The initial FLV was 1584 (1313-1927) mL. The FLV was 1438 (1204-1896) mL after the first procedure and 1470 (1172-1699) mL after the second procedure (P<0.001). After the second procedure, a total of ten patients (12%) had a residual liver volume of less than 75% of the initial liver volume. The 5-year overall survival was 37 (26-54)% after the second procedure. Conclusion: Small changes in FLV were found after two hepatic procedures but with considerable inter-individual variation. Patients selected for a repeated hepatic procedure for recurrent CRLM had an acceptable survival.
|
|
