| 11. |
- Dahlin, Erik, et al.
(författare)
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Outcome of simple decompression of the compressed ulnar nerve at the elbow – influence of smoking, gender, and electrophysiological findings
- 2017
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Ingår i: Journal of Plastic Surgery and Hand Surgery. - 2000-656X. ; 51:2, s. 149-155
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Tidskriftsartikel (refereegranskat)abstract
- Background: Compression of the ulnar nerve at elbow is frequently treated with simple decompression. Knowledge about factors influencing results of surgery of the nerve is limited and contradictory. The primary aim was to evaluate outcome of simple decompression of the nerve using a QuickDASH questionnaire, and to investigate any influence of smoking, gender, and preoperative electrophysiological findings. A second aim was to estimate the relation between QuickDASH score and a clinical assessment of outcome by the surgeon. Methods: Patients who were operated on with simple decompression of the ulnar nerve, excluding reoperations, from September 2009 to February 2011 were evaluated before and at 1 year after surgery using QuickDASH. Data were collected from medical records and from a self-reported health declaration. Results: There were no differences in QuickDASH scores or change in total score between smokers and non-smokers or between women and men. Nerve pathology, assessed by preoperative electrophysiology, did not affect outcome. The surgeon’s assessment of outcome mirrored QuickDASH score. Among all patients, 12/33 (36%) did not have a decrease in QuickDASH score >8, which is considered as a minimal clinically important difference. Conclusion: Smoking, gender, and preoperative electrophysiological findings do not affect outcome of surgery. There are a high number of patients who do not benefit from simple decompression of the ulnar nerve at the elbow. Patients who are planned for surgery should be informed that there is a risk for persistent problems. A simple outcome assessment by the surgeon mirrors QuickDASH score at 1 year.
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| 12. |
- Dahlin, Lars, et al.
(författare)
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Impact of smoking and preoperative electrophysiology on outcome after open carpal tunnel release
- 2017
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Ingår i: Journal of Plastic Surgery and Hand Surgery. - 2000-656X. ; 51:5, s. 329-335
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim was to evaluate the influence of smoking and preoperative electrophysiology on the outcome of open carpal tunnel release. Methods: This retrospective observational study evaluated the outcome in 493 patients (531 hands) primary operated for carpal tunnel syndrome. Data were collected from medical records, health evaluations, and QuickDASH questionnaires before surgery and 1 year after. Results: Smokers had a higher QuickDASH score preoperatively as well as postoperatively, but the change in total score did not differ. The odds of having a postoperative QuickDASH score >10 were 2.5 times higher in smoking patients than in non-smoking patients. In 124/493 patients (25%), no clinically significant improvement was seen. Normal and extreme preoperative electrophysiology values were associated with higher postoperative scores. No correlation was found between preoperative QuickDASH scores and preoperative electrophysiology values. Conclusions: Smokers with carpal tunnel syndrome experience more symptoms preoperatively. Smokers have remaining symptoms after surgery. There is no correlation between preoperative QuickDASH scores and preoperative electrophysiology values. Patients with normal or near to normal preoperative electrophysiology results have limited improvement after surgery.
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| 13. |
- Gaulton, Kyle J, et al.
(författare)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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| 14. |
- Jackson, Victoria E, et al.
(författare)
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Meta-analysis of exome array data identifies six novel genetic loci for lung function.
- 2018
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Ingår i: Wellcome open research. - : F1000 Research Ltd. - 2398-502X. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV 1), forced vital capacity (FVC) and the ratio of FEV 1 to FVC (FEV 1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10 -7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs ( SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.
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| 15. |
- Jørgsholm, Peter, et al.
(författare)
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MRI shows a high incidence of carpal fractures in children with posttraumatic radial-sided wrist tenderness
- 2016
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 87:5, s. 533-537
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose — The epidemiology and optimal diagnostics of wrist injuries in children are not known. We describe fractures revealed by magnetic resonance imaging (MRI) in a prospective population of children and adolescents with posttraumatic radial-sided wrist tenderness, and compare the diagnostic value of radiographs and computed tomography (CT) with that of MRI. Patients and methods — From 2004 to 2007, patients less than 18 years of age who presented at our emergency department were included in the study. 90 wrists in 89 patients underwent clinical, radiographic, and low-field MRI investigation. If plain radiographs or MRI revealed a scaphoid fracture, a supplementary CT scan was performed. Sensitivity and specificity of radiographs and CT for diagnosis of scaphoid fractures was calculated using MRI as the reference standard. Results — 74 fractures were diagnosed in 61 of 90 wrists using MRI; 48 wrists had a scaphoid fracture, 8 had a distal radius fracture, 7 had a capitate fracture, and 3 had a triquetrum fracture. The most common combination of fractures was scaphoid and capitate. The sensitivity of radiographs for visualization of scaphoid fractures was 54% and the specificity was 100%. The sensitivity for other fractures was
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| 16. |
- Larsen, Lars Bruun, et al.
(författare)
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Targeted prevention in primary care aimed at lifestyle-related diseases : A study protocol for a non-randomised pilot study
- 2018
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Ingår i: BMC Family Practice. - : Springer Science and Business Media LLC. - 1471-2296. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The consequences of lifestyle-related disease represent a major burden for the individual as well as for society at large. Individual preventive health checks to the general population have been suggested as a mean to reduce the burden of lifestyle-related diseases, though with mixed evidence on effectiveness. Several systematic reviews, on the other hand, suggest that health checks targeting people at high risk of chronic lifestyle-related diseases may be more effective. The evidence is however very limited. To effectively target people at high risk of lifestyle-related disease, there is a substantial need to advance and implement evidence-based health strategies and interventions that facilitate the identification and management of people at high risk. This paper reports on a non-randomized pilot study carried out to test the acceptability, feasibility and short-term effects of a healthcare intervention in primary care designed to systematically identify persons at risk of developing lifestyle-related disease or who engage in health-risk behavior, and provide targeted and coherent preventive services to these individuals. Methods: The intervention took place over a three-month period from September 2016 to December 2016. Taking a two-pronged approach, the design included both a joint and a targeted intervention. The former was directed at the entire population, while the latter specifically focused on patients at high risk of a lifestyle-related disease and/or who engage in health-risk behavior. The intervention was facilitated by a digital support system. The evaluation of the pilot will comprise both quantitative and qualitative research methods. All outcome measures are based on validated instruments and aim to provide results pertaining to intervention acceptability, feasibility, and short-term effects. Discussion: This pilot study will provide a solid empirical base from which to plan and implement a full-scale randomized study with the central aim of determining the efficacy of a preventive health intervention. Trial registration: Registered at Clinical Trial Gov (Unique Protocol ID: TOFpilot2016). Registered 29 April 2016. The study adheres to the SPIRIT guidelines.
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| 17. |
- Law, Philip J., et al.
(författare)
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Genome-wide association analysis of chronic lymphocytic leukaemia, Hodgkin lymphoma and multiple myeloma identifies pleiotropic risk loci
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- B-cell malignancies (BCM) originate from the same cell of origin, but at different maturation stages and have distinct clinical phenotypes. Although genetic risk variants for individual BCMs have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. We explored genome-wide association studies of chronic lymphocytic leukaemia (CLL, N = 1,842), Hodgkin lymphoma (HL, N = 1,465) and multiple myeloma (MM, N = 3,790). We identified a novel pleiotropic risk locus at 3q22.2 (NCK1, rs11715604, P = 1.60 × 10-9) with opposing effects between CLL (P = 1.97 × 10-8) and HL (P = 3.31 × 10-3). Eight established non-HLA risk loci showed pleiotropic associations. Within the HLA region, Ser37 + Phe37 in HLA-DRB1 (P = 1.84 × 10-12) was associated with increased CLL and HL risk (P = 4.68 × 10-12), and reduced MM risk (P = 1.12 × 10-2), and Gly70 in HLA-DQB1 (P = 3.15 × 10-10) showed opposing effects between CLL (P = 3.52 × 10-3) and HL (P = 3.41 × 10-9). By integrating eQTL, Hi-C and ChIP-seq data, we show that the pleiotropic risk loci are enriched for B-cell regulatory elements, as well as an over-representation of binding of key B-cell transcription factors. These data identify shared biological pathways influencing the development of CLL, HL and MM. The identification of these risk loci furthers our understanding of the aetiological basis of BCMs.
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| 18. |
- Mitchell, Jonathan S., et al.
(författare)
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Genome-wide association study identifies multiple susceptibility loci for multiple myeloma
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P = 1.31 x 10(-8)), 6q21 (rs9372120, P = 9.09 x 10(-15)), 7q36.1 (rs7781265, P = 9.71 x 10(-9)), 8q24.21 (rs1948915, P = 4.20 x 10(-11)), 9p21.3 (rs2811710, P = 1.72 x 10(-13)), 10p12.1 (rs2790457, P = 1.77 x 10(-8)), 16q23.1 (rs7193541, P = 5.00 x 10(-12)) and 20q13.13 (rs6066835, P = 1.36 x 10(-13)), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development.
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| 19. |
- Mohseni, Simin, et al.
(författare)
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Longitudinal study of neuropathy, microangiopathy, and autophagy in sural nerve : Implications for diabetic neuropathy
- 2017
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Ingår i: Brain and Behavior. - : Wiley Online Library. - 2162-3279. ; 7:8
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Tidskriftsartikel (refereegranskat)abstract
- The progression and pathophysiology of neuropathy in impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) is poorly understood, especially in relation to autophagy. This study was designed to assess whether the presence of autophagy-related structures was associated with sural nerve fiber pathology, and to investigate if endoneurial capillary pathology could predict the development of T2DM and neuropathy. Sural nerve physiology and ultrastructural morphology were studied at baseline and 11 years later in subjects with normal glucose tolerance (NGT), IGT, and T2DM. Subjects with T2DM had significantly lower sural nerve amplitude compared to subjects with NGT and IGT at baseline. Myelinated and unmyelinated fiber, endoneurial capillary morphology, and the presence and distribution of autophagy structures were comparable between groups at baseline, except for a smaller myelinated axon diameter in subjects with T2DM and IGT compared to NGT. The baseline values of the subjects with NGT and IGT who converted to T2DM 11 years later demonstrated healthy smaller endoneurial capillary and higher g-ratio versus subjects who remained NGT. At follow-up, T2DM showed a reduction in nerve conduction, amplitude, myelinated fiber density, unmyelinated axon diameter, and autophagy structures in myelinated axons. Endothelial cell area and total diffusion barrier was increased versus baseline. We conclude that small healthy endoneurial capillary may presage the development of T2DM and neuropathy. Autophagy occurs in human sural nerves and can be affected by T2DM. Further studies are warranted to understand the role of autophagy in diabetic neuropathy.
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| 20. |
- Osman, Ayman A. M., et al.
(författare)
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Autophagy in the posterior interosseous nerve of patients with type 1 and type 2 diabetes mellitus: an ultrastructural study
- 2015
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 58:3, s. 625-632
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Tidskriftsartikel (refereegranskat)abstract
- We addressed the question of whether the autophagy pathway occurs in human peripheral nerves and whether this pathway is associated with peripheral neuropathy in diabetes mellitus. By using electron microscopy, we evaluated the presence of autophagy-related structures and neuropathy in the posterior interosseous nerve of patients who had undergone carpal tunnel release and had type 1 or type 2 diabetes mellitus, and in patients with no diabetes (controls). Autophagy-related ultrastructures were observed in the samples taken from all patients of the three groups. The number of autophagy-associated structures was significantly higher (p < 0.05) in the nerves of patients with type 1 than type 2 diabetes. Qualitative and quantitative evaluations of fascicle area, diameter of myelinated and unmyelinated nerve fibres, the density of myelinated and unmyelinated fibres and the g-ratio of myelinated fibres were performed. We found degeneration and regeneration of a few myelinated axons in controls, and a well-developed neuropathy with the loss of large myelinated axons and the presence of many small ones in patients with diabetes. The pathology in type 1 diabetes was more extensive than in type 2 diabetes. The results of this study show that the human peripheral nerves have access to the autophagy machinery, and this pathway may be regulated differently in type 1 and type 2 diabetes; insulin, presence of extensive neuropathy, and/or other factors such as duration of diabetes and HbA(1c) level may underlie this differential regulation.
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