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- Améen, Caroline, 1975, et al.
(författare)
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Activation of peroxisome proliferator-activated receptor alpha increases the expression and activity of microsomal triglyceride transfer protein in the liver
- 2005
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Ingår i: J Biol Chem. ; 280:2, s. 1224-9
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Tidskriftsartikel (refereegranskat)abstract
- Microsomal triglyceride transfer protein (MTP) is rate-limiting in the assembly and secretion of lipoproteins containing apolipoprotein (apo) B. Previously we demonstrated that Wy 14,643 (Wy), a peroxisome proliferator-activated receptor (PPAR) alpha agonist, increases apoB-100 secretion despite decreased triglyceride synthesis. In this study, we sought to determine whether PPARalpha activation increases MTP expression and activity. Treatment with Wy increased hepatic MTP expression and activity in rats and mice and increased MTP expression in primary cultures of rat and mouse hepatocytes. Addition of actinomycin D blocked this increase and the MTP promoter (-136 to +67) containing a conserved DR1 element was activated by Wy, showing that PPARalpha activates transcription of the gene. Wy did not affect MTP expression in the intestine or in cultured hepatocytes from PPARalpha-null mice. A retinoid X receptor agonist (9-cis-retinoic acid), but not a PPARgamma agonist (rosiglitazone), increased MTP mRNA expression in cultured hepatocytes from both wild type and PPARalpha-null mice. In rat hepatocytes incubated with Wy, MTP mRNA levels increased between 6 and 24 h, and MTP protein expression and apoB-100 secretion increased between 24 and 72 h. In conclusion, PPARalpha activation stimulates hepatic MTP expression via increased transcription of the Mtp gene. This effect is paralleled by a change in apoB-100 secretion, indicating that the effect of Wy on apoB-100 secretion is mediated by increased expression of MTP.
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- Bahlmann, Hans, 1973-
(författare)
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Goal-directed fluid therapy during major abdominal surgery
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Both hypo- and hypervolemia increase the risk for postoperative complications after major abdominal surgery. Fluid needs vary amongst patients depending on differences in preoperative dehydration, intraoperative physiology and surgical characteristics. Goal-directed fluid therapy (GDFT) aims to target the right amount of fluid administration in each patient by evaluating the effect of fluid boluses on haemodynamic parameters such as stroke volume. It has been shown to reduce postoperative morbidity and is generally recommended for high-risk surgery. The overall aim of this thesis was to evaluate whether more simple devices for GDFT result in clinical benefit, thus facilitating the application of GDFT in more patients.Aim: To compare performance and clinical benefit of pleth variability index (PVI), a noninvasive, easy-to-use device for GDFT, with the reference method of oesophageal Doppler; to evaluate methods for measuring preoperative dehydration and its effect on fluid handling by the body; and to confirm the expected clinical benefits of GDFT in patients undergoing oesophageal resection, a high risk procedure.Methods: In Studies I-III 150 patients scheduled for open abdominal surgery of at least 2 hrs were randomised to GDFT with either PVI or oesophageal Doppler. In the first half of the cohort, both monitors were connected to compare intraoperative performance. In 30 patients preoperative dehydration was analysed. In study IV 64 patients undergoing oesophageal resection were randomised to GDFT using pulse contour analysis or standard treatment.Results: The concordance between PVI and oesophageal Doppler for indicating the need for and effect of a fluid bolus was low, and both had only limited capacity to predict the effect of a fluid bolus. Both methods resulted in comparable amounts of fluid being administered and similar clinical outcome. Preoperative dehydration was limited but did impact on fluid handling. Patients receiving GDFT during oesophageal resection received more fluid and more dobutamine compared to controls, but this did not result in any clinical benefit.Conclusions: There are methodological issues as well as uncertainties about the clinical benefit of GDFT. We cannot recommend a strict application of any GDFT strategy, but suggest that its components should be incorporated in a more encompassing assessment of a patient’s fluid needs. The measurement, impact and treatment of preoperative dehydration need to be further clarified.
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- de Geer, Lina, 1974-, et al.
(författare)
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No association with cardiac death after sepsis : A nationwide observational cohort study
- 2019
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley-Blackwell Publishing Inc.. - 0001-5172 .- 1399-6576. ; 63:3, s. 344-351
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cardiac dysfunction is a well-known complication of sepsis, but its long-term consequences and implications for patients remain unclear. The aim of this study was to investigate cardiac outcome in sepsis by assessing causes of death up to 2 years after treatment in an Intensive Care Unit (ICU) in a nationwide register-based cohort collected from the Swedish Intensive Care Registry.METHODS: A cohort of 13 669 sepsis and septic shock ICU patients from 2008 to 2014 was collected together with a non-septic control group, matched regarding age, sex and severity of illness (n = 6582), and all without preceding severe cardiac disease. For a large proportion of the severe sepsis and septic shock patients (n = 7087), no matches were found. Information on causes of death up to 2 years after ICU admission was sought in the Swedish National Board of Health and Welfare's Cause of Death Registry.RESULTS: Intensive Care Unit mortality was nearly identical in a matched comparison of sepsis patients to controls (24% in both groups) but higher in more severely ill sepsis patients for whom no matches were found (33% vs 24%, P < 0.001). There was no association of sepsis to cardiac deaths in the first month (OR 1.03, 95%CI 0.87 to 1.20, P = 0.76) nor up to 2 years after ICU admission (OR 1.01, 95%CI 0.82 to 1.25, P = 0.94) in an adjusted between-group comparison.CONCLUSIONS: There was no association with an increased risk of death related to cardiac disease in patients with severe sepsis or septic shock when compared to other ICU patients with similar severity of illness.
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- Kareliusson, Frida, et al.
(författare)
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Risk prediction of ICU readmission in a mixed surgical and medical population
- 2015
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Ingår i: Journal of Intensive Care. - : BioMed Central (BMC). - 2052-0492. ; 3:30
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundReadmission to intensive care units (ICU) is accompanied with longer ICU stay as well as higher ICU, in-hospital and 30-day mortality. Different scoring systems have been used in order to predict and reduce readmission rates.MethodsThe purpose of this study was to evaluate the Stability and Workload Index for Transfer (SWIFT) score as a predictor of readmission. Further, we wanted to study steps and measures taken at the ward prior to readmission.ResultsThis was a retrospective study conducted at the mixed surgical and medical ICU at Linköping University Hospital. One thousand sixty-seven patients >18 years were admitted to the ICU during 2 years and were included in the study. During the study period, 27 patients were readmitted to the ICU. Readmitted patients had a higher SWIFT score than the non-readmitted (16.1 ± 6.8 vs. 13.0 ± 7.5, p = 0.03) at discharge. The total ICU length of stay was longer (7.5 ± 7.5 vs. 2.9 ± 5.1, p = 0.004), and the 30-day mortality was higher (26 vs. 7 %, p < 0.001) for readmitted patients. Fifty-six percent of readmitted patients were assessed by the critical care outreach service (CCOS) at the ward prior to ICU readmission. A SWIFT score of 15 or more was associated with a significantly higher readmission rate (p = 0.03) as well as 30-day mortality (p < 0.001) compared to a score of ≤14.ConclusionsA SWIFT score of 15 or more is associated with higher readmission rate and 30-day mortality. The SWIFT score could therefore be used for risk prediction for readmission and mortality at ICU discharge.
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- Oscarsson Tibblin, Anna, 1965-
(författare)
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Perioperative myocardial damage and cardiac outcome in patients-at-risk undergoing non-cardiac surgery
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Despite increasingly sophisticated perioperative management, cardiovascular complications continue to be major challenges for the clinician. As a growing number of elderly patients with known coronary artery disease (CAD) or with risk factors for CAD are undergoing non-cardiac surgery, cardiovascular complications will remain a significant clinical problem in the future.The overall objective of this thesis was to study the incidence of myocardial damage and perioperative adverse cardiac events, to determine predictors of poor outcome and to assess the effect of a medical intervention in patients at risk undergoing non-cardiac surgery.The studies in this thesis were conducted on a total of 952 patients undergoing non-cardiac surgery. Studies I and IV were multicenter studies; whereas the patients included in studies II and III underwent non-cardiac surgery at Linkoping University Hospital, Sweden. The correlation between postoperative myocardial damage and short- and long-term outcome were studied in 546 patients, aged 70 years or older undergoing non-cardiac surgery of at least 30 minutes duration. This study showed a close correlation between postoperative myocardial damage and poor short- as well as long-term outcome. Elevated Troponin T was a strong independent predictor of mortality within one year of surgery. In 186 patients with ASA physical status classification III or IV undergoing non-elective surgery, the incidence of myocardial damage was 33%. In this study preoperative myocardial damage was an independent predictor of major adverse cardiac events in the postoperative period. In 69 patients with ASA physical status classification III & IV undergoing acute hip surgery, we found a close correlation between elevated NT-proBNP value prior to surgery and cardiac complications in the postoperative period. To study the effect of acetylsalicylic acid on postoperative myocardial damage and cardiovascular events, 220 patients at risk were randomized to receive 75 mg of acetylsalicylic acid or placebo 7 days prior to surgery until the third postoperative day. This study showed that treatment with acetylsalicylic acid resulted in an 8% (95% CI 1-15%) absolute risk reduction of having a postoperative major adverse cardiac event. No statistically significant differences of bleeding complications were seen between the groups.In conclusion, this thesis contributes to the understanding of the clinical relevance of elevated cardiac markers (with or without clinical or ECG signs of myocardial damage) in patients undergoing elective or emergency surgery. Moreover, we have identified predictors of poor outcome in the perioperative period that could be used as tools for identifying patients at risk. Finally, we have shown that continuing acetylsalicylic acid in the perioperative period reduced the risk of major adverse cardiac events within 30 days of surgery.
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