| 1. |
- Sjöberg, Mats, et al.
(författare)
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Infliximab as rescue therapy in hospitalised patients with steroid-refractory acute ulcerative colitis: a long-term follow-up of 211 Swedish patients
- 2013
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley-Blackwell. - 0269-2813 .- 1365-2036. ; 38:4, s. 377-387
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRescue therapy with infliximab (IFX) has been proven effective in a steroid-refractory attack of ulcerative colitis (UC). The long-term efficacy is not well described. less thanbrgreater than less thanbrgreater thanAimTo present a retrospective study of IFX as rescue therapy in UC. Primary end points were colectomy-free survival at 3 and 12months. less thanbrgreater than less thanbrgreater thanMethodsIn this multicentre study, 211 adult patients hospitalised between 1999 and 2010 received IFX 5mg/kg as rescue therapy due to a steroid-refractory, moderate-to-severe attack of UC. Exclusion criteria were duration of current flare for andgt;12weeks, corticosteroid treatment for andgt;8weeks before hospitalisation, previous IFX therapy or Crohns disease. less thanbrgreater than less thanbrgreater thanResultsProbability of colectomy-free survival at 3months was 0.71 (95% CI, 0.64-0.77), at 12months 0.64 (95% CI, 0.57-0.70), at 3years 0.59 (95% CI, 0.52-0.66) and at 5years 0.53 (95% CI, 0.44-0.61). Steroid-free, clinical remission was achieved in 105/211 (50%) and 112/209 (54%) patients at 3 and 12months respectively. Of 75 colectomies during the first year, 48 (64%) were carried out during the first 14days, 13 (17%) on days 15-90 and 14 (19%) between 3 and 12months. There were three (1.4%) deaths during the first 3months. less thanbrgreater than less thanbrgreater thanConclusionsInfliximab is an effective rescue treatment, both short- and long-term, in a steroid-refractory attack of UC. Most IFX failures underwent surgery during the first 14days, which calls for studies on how to optimise induction treatment with IFX. Serious complications, including mortality, were rare.
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| 4. |
- Siekmann, Wiebke, 1978-, et al.
(författare)
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Surgical and not analgesic technique affects postoperative inflammation following colorectal cancer surgery : a prospective, randomized study
- 2017
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Ingår i: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 19:6, s. 186-195
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Epidural analgesia reduces the surgical stress response. However, its effect on pro- and anti-inflammatory cytokines in the genesis of inflammation following major abdominal surgery remains unclear. Our main objective was to elucidate whether perioperative epidural analgesia prevents the inflammatory response following colorectal cancer surgery.METHODS: Ninety-six patients scheduled for open or laparoscopic surgery were randomized to epidural analgesia (group E) or patient-controlled intravenous analgesia (group P). Surgery and anaesthesia were standardized in both groups. Plasma cortisol, insulin and serum cytokines [interleukin 1β (IL-1β), IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumour necrosis factor α, interferon γ, granulocyte-macrophage colony-stimulating factor, prostaglandin E2 and vascular endothelial growth factor] were measured preoperatively (T0), 1-6 h postoperatively (T1) and 3-5 days postoperatively (T2). Mixed model analysis was used, after logarithmic transformation when appropriate, for analyses of cytokines and stress markers.RESULTS: >There were no significant differences in any serum cytokine concentration between groups P and E at any time point except for IL-10 which was 87% higher in group P [median and range 4.1 (2.3-9.2) pg/ml] compared to group E [2.6 (1.3-4.7) pg/ml] (P = 0.002) at T1. There was no difference in plasma cortisol and insulin between the groups at any time point after surgery. A significant difference in median serum cytokine concentration was found between open and laparoscopic surgery with higher levels of IL-6, IL-8 and IL-10 at T1 in patients undergoing open surgery compared to laparoscopic surgery. No difference in serum cytokine concentration was detected between the groups or between the surgical technique at T2.CONCLUSIONS: Open surgery, compared to laparoscopic surgery, has greater impact on these inflammatory mediators than epidural analgesia vs intravenous analgesia.
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| 5. |
- Fadl, Helena, 1965-, et al.
(författare)
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Changing diagnostic criteria for gestational diabetes in Sweden-a stepped wedge national cluster randomised controlled trial-the CDC4G study protocol
- 2019
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Ingår i: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The optimal criteria to diagnose gestational diabetes mellitus (GDM) remain contested. The Swedish National Board of Health introduced the 2013 WHO criteria in 2015 as a recommendation for initiation of treatment for hyperglycaemia during pregnancy. With variation in GDM screening and diagnostic practice across the country, it was agreed that the shift to new guidelines should be in a scientific and structured way. The aim of the Changing Diagnostic Criteria for Gestational Diabetes (CDC4G) in Sweden () is to evaluate the clinical and health economic impacts of changing diagnostic criteria for GDM in Sweden and to create a prospective cohort to compare the many long-term outcomes in mother and baby under the old and new diagnostic approaches. Methods This is a stepped wedge cluster randomised controlled trial, comparing pregnancy outcomes before and after the switch in GDM criteria across 11 centres in a randomised manner. The trial includes all pregnant women screened for GDM across the participating centres during January-December 2018, approximately two thirds of all pregnancies in Sweden in a year. Women with pre-existing diabetes will be excluded. Data will be collected through the national Swedish Pregnancy register and for follow up studies other health registers will be included. Discussion The stepped wedge RCT was chosen to be the best study design for evaluating the shift from old to new diagnostic criteria of GDM in Sweden. The national quality registers provide data on the whole pregnant population and gives a possibility for follow up studies of both mother and child. The health economic analysis from the study will give a solid evidence base for future changes in order to improve immediate pregnancy, as well as long term, outcomes for mother and child.
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| 6. |
- Fadl, Helena, 1965-, et al.
(författare)
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Gestational diabetes mellitus and later cardiovascular disease : a Swedish population based case-control study
- 2014
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Ingår i: British Journal of Obstetrics and Gynecology. - : Wiley-Blackwell. - 1470-0328 .- 1471-0528. ; 121:12, s. 1530-1536
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To identify if gestational diabetes mellitus (GDM) is a clinically useful marker of future cardiovascular disease (CVD) risk and if GDM combined with other risks (smoking, hypertension or body mass) identifies high-risk groups.Design: Population-based matched case-control study.Setting: National Swedish register data from 1991 to 2008.Population: A total of 2639 women with a cardiovascular event and matched controls.Methods: Conditional logistic regression examined associations with CVD before and after adjustment for conventional risk factors and confounders. Effect modification for the association of GDM with CVD by body mass index (BMI), smoking and chronic hypertension was assessed by stratification and interaction testing. Adjustment for diabetes post-pregnancy evaluated its mediating role.Main outcome measures: Inpatient diagnoses or causes of death identifying ischemic heart disease, ischemic stroke, atherosclerosis or peripheral vascular disease.Results: The adjusted odds ratios (and 95% confidence intervals) for the association of CVD with GDM are 1.51 (1.07-2.14), 2.23 (2.01-2.48) for smoking, 1.98 (1.71-2.29) for obesity and 5.10 (3.18-8.18) for chronic hypertension. In stratified analysis the association of CVD with GDM was only seen among women with BMI 25, with an odds ratio of 2.39 (1.39-4.10), but only women with a BMI <30 accounted for this increased risk. Adjustment for post-pregnancy diabetes attenuated it somewhat to 1.99 (1.13-3.52).Conclusions: In the absence of other recognised cardiovascular risk factors, such as smoking, obesity or chronic hypertension, GDM is a useful marker of raised CVD risk among women with BMI between 25 and 29.
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| 7. |
- Gustavsson, Anders, et al.
(författare)
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Clinical trial : colectomy after rescue therapy in ulcerative colitis-3-year follow-up of the Swedish-Danish controlled infliximab study
- 2010
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 32:8, s. 984-989
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Tidskriftsartikel (refereegranskat)abstract
- Background The long-term efficacy of infliximab as rescue therapy in steroid-refractory ulcerative colitis is not well described. Aim To examine the long-term efficacy of infliximab as a rescue therapy through a 3-year follow-up of a previous placebo-controlled trial of infliximab in acute steroid-refractory ulcerative colitis. Method In the original study, 45 patients were randomized to a single infusion of infliximab 5 mg/kg or placebo, and at 3 months, 7/24 patients given infliximab were operated vs. 14/21 patients given placebo. Three years or later, patients were asked to participate in a clinical follow-up. Results Another seven patients underwent colectomy during follow-up: five in the infliximab group and two in the placebo group. After 3 years, a total of 12/24 (50%) patients given infliximab and 16/21 (76%) given placebo (P = 0.012) had a colectomy. None of eight patients in endoscopic remission at 3 months later had a colectomy compared with 7/14 (50%) patients who were not in remission (P = 0.02). There was no mortality. Conclusion The benefit of rescue therapy with infliximab in steroid-refractory acute ulcerative colitis remained after 3 years. The main advantage of infliximab treatment occurred during the first 3 months, whereas subsequent colectomy rates were similar in the two groups. Mucosal healing at 3 months influenced later risk of colectomy.
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| 8. |
- Hildén, K., et al.
(författare)
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Gestational diabetes and adiposity are independent risk factors for perinatal outcomes : a population based cohort study in Sweden
- 2019
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Ingår i: Diabetic Medicine. - : Wiley-Blackwell Publishing Inc.. - 0742-3071 .- 1464-5491. ; 36:2, s. 151-157
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To evaluate the interaction effects of gestational diabetes (GDM) with obesity on perinatal outcomes.METHODS: A population-based cohort study in Sweden excluding women without pre-gestational diabetes with a singleton birth between 1998 and 2012. Logistic regression was performed to evaluate the potential independent associations of GDM and BMI with adverse perinatal outcomes as well as their interactions. Main outcome measures were malformations, stillbirths, perinatal mortality, low Apgar score, fetal distress, prematurity and Erb's palsy.RESULTS: ) had significantly increased risks of all outcomes including stillbirth 1.51 (1.40-1.62) to 2.85 (2.52-3.22) and perinatal mortality 1.49 (1.40-1.59) to 2.83 (2.54-3.15).CONCLUSIONS: There is no interaction effect between GDM and BMI for the studied outcomes. Higher BMI and GDM are major independent risk factors for most serious adverse perinatal outcomes. More effective pre-pregnancy and antenatal interventions are required to prevent serious adverse pregnancy outcomes among women with either GDM or high BMI.
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| 9. |
- Iannelli, F, et al.
(författare)
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A damaged genome's transcriptional landscape through multilayered expression profiling around in situ-mapped DNA double-strand breaks
- 2017
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8, s. 15656-
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Tidskriftsartikel (refereegranskat)abstract
- Of the many types of DNA damage, DNA double-strand breaks (DSBs) are probably the most deleterious. Mounting evidence points to an intricate relationship between DSBs and transcription. A cell system in which the impact on transcription can be investigated at precisely mapped genomic DSBs is essential to study this relationship. Here in a human cell line, we map genome-wide and at high resolution the DSBs induced by a restriction enzyme, and we characterize their impact on gene expression by four independent approaches by monitoring steady-state RNA levels, rates of RNA synthesis, transcription initiation and RNA polymerase II elongation. We consistently observe transcriptional repression in proximity to DSBs. Downregulation of transcription depends on ATM kinase activity and on the distance from the DSB. Our study couples for the first time, to the best of our knowledge, high-resolution mapping of DSBs with multilayered transcriptomics to dissect the events shaping gene expression after DSB induction at multiple endogenous sites.
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| 10. |
- Jansson, Kjell, 1958-, et al.
(författare)
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Normal values and differences between intraperitoneal and subcutaneous microdialysis in patients after non‐complicated gastrointestinal surgery
- 2005
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 65:4, s. 273-282
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Visceral ischemia is an early event in the development of shock and organ failure. Microdialysis has been presented as a promising method for detection of visceral hypoxia and ischemia. The aim of this study was to investigate differences in the metabolic response measured by microdialysis between intraperitoneal and subcutaneous locations and to estimate normal values of lactate/pyruvate ratio, glucose and glycerol. Material and methods. Intraperitoneal and subcutaneous metabolic responses were compared regarding lacate/pyruvate ratio, glucose and glycerol, during 45 postoperative hours in 33 patients undergoing various non‐complicated elective major gastrointestinal surgery. Results. Intraperitoneal lactate/pyruvate ratio started around 15 and decreased over time, while subcutaneous levels were stable around 9. Glucose levels were higher intraperitoneally and increased rapidly during the first 9 h to 8.6 mM, while the subcutaneous levels increased during 21 h to 7.5 mM. Intraperitoneal glycerol levels were stable around 100 µM, while subcutaneous values started around 230 µM and then increased. Conclusions. In a non‐complicated postoperative course the lactate/pyruvate ratio and glucose levels are higher intraperitoneally, suggesting a higher postoperative intraperitoneal metabolism. Glycerol levels are higher and increase subcutaneously, suggesting increased postoperative energy demand, particularly in the visceral organs, as being responsible for the lipolysis seen in the subcutaneous tissue.
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