| 1. |
- Adrianto, Indra, et al.
(författare)
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Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:3, s. 253-258
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE, MIM152700) is an autoimmune disease characterized by self-reactive antibodies resulting in systemic inflammation and organ failure. TNFAIP3, encoding the ubiquitin-modifying enzyme A20, is an established susceptibility locus for SLE. By fine mapping and genomic re-sequencing in ethnically diverse populations, we fully characterized the TNFAIP3 risk haplotype and identified a TT>A polymorphic dinucleotide (deletion T followed by a T to A transversion) associated with SLE in subjects of European (P = 1.58 x 10(-8), odds ratio = 1.70) and Korean (P = 8.33 x 10(-10), odds ratio = 2.54) ancestry. This variant, located in a region of high conservation and regulatory potential, bound a nuclear protein complex composed of NF-kappa B subunits with reduced avidity. Further, compared with the non-risk haplotype, the haplotype carrying this variant resulted in reduced TNFAIP3 mRNA and A20 protein expression. These results establish this TT>A variant as the most likely functional polymorphism responsible for the association between TNFAIP3 and SLE.
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| 3. |
- Backman, Olof, et al.
(författare)
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Laparoscopic Roux-en-Y Gastric Bypass Without Division of the Mesentery Reduces the Risk of Postoperative Complications
- 2019
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Ingår i: Surgical Endoscopy. - : Springer. - 0930-2794 .- 1432-2218. ; 33:9, s. 2858-2863
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Tidskriftsartikel (refereegranskat)abstract
- Background: Anastomotic complications after laparoscopic Roux-en-Y gastric bypass (LRYGB) including leaks, ulceration, and stenosis remain a significant cause of post-operative morbidity and mortality. Our objective was to compare two different surgical techniques regarding short-term anastomotic complications.Methods: A retrospective analysis of all patients operated with a primary LRYGB from 2006 to June 2015 in one institution, where prospectively collected data from an internal quality registry and medical journals were analyzed.Results: In total, 2420 patients were included in the analysis. 1016 were operated with a technique where the mesentery was divided during the creation of the Roux-limb (DM-LRYGB) and 1404 were operated with a method where the mesentery was left intact (IM-LRYGB). Leakage in the first 30 days [2.6% vs. 1.1% (p < 0.05)], and ulceration or stenosis occurring during the first 6 months after surgery [5.6% vs. 0.1% (p < 0.05)] was significantly higher in the DM-LRYGB group. Adjusted odds ratio for anastomotic leak was 0.46 (95% CI 0.24-0.87) and for stenosis/ulceration 0.01 (95% CI 0.002-0.09).Conclusion: IM-LRYGB seems to reduce the risk of complications at the anastomosis. A plausible explanation for this is that the blood supply to the anastomosis is compromised when the mesentery is divided.
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| 4. |
- Benedict, G. Fritz, et al.
(författare)
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Distance scale zero points from galactic RR Lyrae star parallaxes
- 2011
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 142:6, s. 187-
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Tidskriftsartikel (refereegranskat)abstract
- We present new absolute trigonometric parallaxes and proper motions for seven Population II variable stars-five RR Lyr variables: RZ Cep, XZ Cyg, SU Dra, RR Lyr, and UV Oct; and two type 2 Cepheids: VY Pyx and kappa Pav. We obtained these results with astrometric data from Fine Guidance Sensors, white-light interferometers on Hubble Space Telescope. We find absolute parallaxes in milliseconds of arc: RZ Cep, 2.12 +/- 0.16 mas; XZ Cyg, 1.67 +/- 0.17 mas; SU Dra, 1.42 +/- 0.16 mas; RR Lyr, 3.77 +/- 0.13 mas; UV Oct, 1.71 +/- 0.10 mas; VY Pyx, 6.44 +/- 0.23 mas; and. Pav, 5.57 +/- 0.28 mas; an average sigma(pi)/pi = 5.4%. With these parallaxes, we compute absolute magnitudes in V and K bandpasses corrected for interstellar extinction and Lutz-Kelker-Hanson bias. Using these RR Lyrae variable star absolute magnitudes, we then derive zero points for M(V)-[Fe/H] and M(K)-[Fe/H]-log P relations. The technique of reduced parallaxes corroborates these results. We employ our new results to determine distances and ages of several Galactic globular clusters and the distance of the Large Magellanic Cloud. The latter is close to that previously derived from Classical Cepheids uncorrected for any metallicity effect, indicating that any such effect is small. We also discuss the somewhat puzzling results obtained for our two type 2 Cepheids.
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| 6. |
- Freedman, Jacob
(författare)
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Bile in the oesophagus contributes to the development and complications of gastro-oesophageal reflux disease
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objective: To clarify the relationship between duodenogastro- oesophageal reflux (DGOR) and gastro- oesophageal reflux disease (GORD) and its complications. Methods: As persons who have had their gallbladders removed have been shown to have an increased incidence of duodenogastric reflux, one would expect them to have an increased incidence of DGOR. Two epidemiological studies, one case-control and one population based, attempted to show an association between cholecystectomy and oesophageal cancer. Furthermore, patients with reflux symptoms twice weekly or more, for at least 6 months, and healthy volunteers were recruited and examined. Upper gastrointestinal endoscopy, circadian oesophageal acidity values, bilirubin levels, oesophageal motility and a study of gastric emptying using a scintigraphic method, were performed to assess DGOR, GORD and foregut motility parameters. Results: A 30% increase in standard incidence ratio was found for cholecystectomised patients as regards to the risk for developing adenocarcinoma of the oesophagus. This increase was not seen for squamous cell carcinoma of the oesophagus. Neither did nonoperated patients with gall-stone disease show any increased risk for the two cancers. The amount of bilirubin detected in the oesophagus showed a significant correlation to impaired oesophageal motility, as measured by the degree of efficiency of its peristaltic contractions. In a multivariate analysis it was found that this effect was correlated to bile reflux but not to acid reflux. Gastric emptying parameters, proximal and total, showed no differences in patients with DGOR compared to a normal material. No correlation was found between the degree of acid or bile reflux in the oesophagus and gastric emptying parameters. Finally, a noramal control group was descriped for combined ambulatory recordings of pH, bilirubin and oesophageal motility. Conclusions: DGOR is of importance in GORD. An increased risk for adenocarcinoma of the oesophagus following cholecystectomy may result from an increase in DGOR. This increased risk is small and does not necessitate any change in our current management of gall stone disease. Impaired oesophageal motility seen with GORD is associated with DGOR but not with acid reflux, however it does not improve after correction for DGOR It is not clear if this impairment is due to structural changes in the oesophageal wall as a result of DGOR or a preexisting condition. There seems to be no general disturbance of foregut motility with DGOR and no correlation between gastric emptying and biliary reflux. DGOR should be taken into consideration when treating patients with reflux disease.
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| 7. |
- Frühling, Petter, et al.
(författare)
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Irreversible electroporation of hepatocellular carcinoma and colorectal cancer liver metastases : A nationwide multicenter study with short- and long-term follow-up
- 2023
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Ingår i: European Journal of Surgical Oncology. - : Elsevier. - 0748-7983 .- 1532-2157. ; 49:11
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: A nationwide multicenter study was performed to examine short- and long-term effects of irreversible electroporation (IRE) for hepatocellular carcinoma (HCC) and colorectal cancer liver metastases (CRCLM). IRE is an alternative method when thermal ablation is contraindicated because of risk for serious thermal complications.Methods: All consecutive patients in Sweden treated with IRE because of HCC or CRCLM, were included between 2011 and 2018. We evaluated medical records and radiological imaging to obtain information regarding patient-, tumor-, and treatment characteristics. We also assessed local tumor progression, and survival.Results: In total 206 tumors in 149 patients were treated with IRE. Eighty-seven patients (58.4%) had colorectal cancer liver metastases, and 62 patients (41.6%) had hepatocellular carcinoma. Median tumor size was 20 mm (i. q.r. 14-26 mm). Median overall survival for CRCLM and HCC, were 27.0 months (95% CI 22.2-31.8 months), and 35.0 months (95% CI 13.8-56.2 months), respectively. Median follow-up time was 58 months (95% CI 50.6-65.4). Local ablation success at six and twelve months for HCC was 58.3% and 40.3%, and for CRCLM 37.7% and 25.4%. The median time to local tumor progression (LTP) for HCC was 21.0 months (95% CI: 9.5-32.5 months), and for CRCLM 6.0 months (95% CI: 4.5-7.5 months). At 30-day follow-up, 15.4% (n = 23) of patients suffered from a complication rated as Clavien-Dindo grade 1-3a. Three patients (2.0%) had grade 3b-5 with one death in a thromboembolic event.Conclusion: IRE is a safe ablation modality for patients with liver tumors that are located in such a way that other treatment options are unsuitable.
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| 8. |
- Galmén, Karolina, et al.
(författare)
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Quantitative assessment of atelectasis formation under high frequency jet ventilation during liver tumour ablation : A computer tomography study
- 2023
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:4
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHigh frequency jet ventilation (HFJV) can be used to minimise sub-diaphragmal organ displacements. Treated patients are in a supine position, under general anaesthesia and fully muscle relaxed. These are factors that are known to contribute to the formation of atelectasis. The HFJV-catheter is inserted freely inside the endotracheal tube and the system is therefore open to atmospheric pressure.AimThe aim of this study was to assess the formation of atelectasis over time during HFJV in patients undergoing liver tumour ablation under general anaesthesia.MethodIn this observational study twenty-five patients were studied. Repeated computed tomography (CT) scans were taken at the start of HFJV and every 15 minutes thereafter up until 45 minutes. From the CT images, four lung compartments were defined: hyperinflated, normoinflated, poorly inflated and atelectatic areas. The extension of each lung compartment was expressed as a percentage of the total lung area.ResultAtelectasis at 30 minutes, 7.9% (SD 3.5, p = 0.002) and at 45 minutes 8,1% (SD 5.2, p = 0.024), was significantly higher compared to baseline 5.6% (SD 2.5). The amount of normoinflated lung volumes were unchanged over the period studied. Only a few minor perioperative respiratory adverse events were noted.ConclusionAtelectasis during HFJV in stereotactic liver tumour ablation increased over the first 45 minutes but tended to stabilise with no impact on normoinflated lung volume. Using HFJV during stereotactic liver ablation is safe regarding formation of atelectasis.
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| 10. |
- Johansen, Karin, 1990-
(författare)
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Effects of Pancreatic Surgery : Quality of Life, Cost-effectiveness and Postoperative Results
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND Pancreatic operations are large procedures with high rates of complications and other potentially impactful consequences such as diabetes and pancreatic exocrine insufficiency. Due to this, and due to the fact that the operations are often occasioned by periampullary tumours with a poor prognosis, it is important to evaluate how the operations affect patients in terms of postoperative results and quality of life. In the constantly developing field of pancreatic surgery, it is also important to evaluate the cost-effectiveness of new methods. METHODS The first study was a register study including all patients in the Swedish National Pancreatic and Periampullary Cancer Registry with a diagnosis from 2010-2018 who underwent pancreaticoduodenectomy (PD). Patients were divided into age groups of <70, 70-79 and ≥80 years old and were compared regarding preoperative, perioperative and postoperative data as well as survival. The second and third studies were based on the randomized controlled trial LAPOP performed in Linköping from 2015-2019 where 60 patients were randomized 1:1 to open or laparoscopic distal pancreatectomy and followed for two years with repeated quality of life questionnaires. For the second study, the EORTC QLQ-C30 and PAN26 questionnaires were collected and compared between groups. For the third study, the EQ-5D questionnaire was used in a cost-effectiveness analysis together with costs collected from patients’ medical records, including all health care-related costs up to 2 years postoperatively. Nonparametric bootstrapping with 10 000 samples was performed to compare quality-adjusted life years (QALYs) and costs between groups. The fourth study was a qualitative interview study in which 20 patients undergoing total pancreatectomy (TP) from 2020-2021 in Linköping or Karolinska University Hospitals were interviewed 6-9 months postoperatively about symptoms and life changes after the operation. RESULTS In the first study, 2793 patients underwent PD in the study period, of which 1137 patients were 70-79 years of age, and 148 patients were ≥80 years of age. There were no significant differences between groups regarding short-term mortality or the rate of severe complications according to the Clavien-Dindo classification of complications. Patients in the two older groups had a worse preoperative condition and a higher rate of medical and some surgical complications postoperatively. In the LAPOP trial, 54 patients were included in the quality of life analysis. There was a significant difference in six of the quality of life-domains measured with QLQ-C30 and PAN26 with better results in the laparoscopic group. When comparing values at the two-year measurement, 3 domains had a significant difference and 16 domains a clinically relevant difference of 10 or more, all with better results in the laparoscopic group. In the cost-effectiveness analysis, 56 patients were included in the analysis. Mean health care costs were €3 863 lower in the laparoscopic group (95% CI: -€8 020 to €385), and the QALYs were 0.08 higher (95% CI: -0.09 to 0.25). In the bootstrap analysis, 79% of samples had higher QALYs and lower costs for the laparoscopic group, and 95% were in favour of laparoscopic resection with a cost-per-QALY threshold of €50 000. Patients undergoing total pancreatectomy voiced symptoms and life changes that revolved around the two main themes: ‘changes in everyday life’ and ‘psychological journey’. In the former, patients described the impact of diabetes, food intake, diarrhoea and the process of recovery, where diabetes in particular appeared to be challenging for some. In the second theme, patients outlined the diagnosis processing, the importance of support from family, friends and the health care system, and a need for more thorough information. CONCLUSIONS Despite a worse preoperative condition, elderly patients undergoing PD did not have an increase in short-term mortality or serious complications. With continued careful preoperative examination, in particular regarding cardiovascular comorbidity, octogenarians can likely safely continue to be offered to undergo PD. After distal pancreatectomy, there was a considerable difference between groups regarding postoperative quality of life in favour of the laparoscopic method, which seemed to remain as long as 2 years postoperatively. The laparoscopic method was also favoured in the cost-effectiveness analysis where it was associated with lower costs and higher QALYs. These results support the ongoing transition from open to minimally invasive distal pancreatectomies. After TP, patients struggle with a lack of support and education, particularly regarding their diabetes treatment. Efforts should be undertaken to improve and standardize the diabetes care for this group.
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