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1.
  • Arora, Satish, et al. (author)
  • Virtual Histology Assessment of Cardiac Allograft Vasculopathy Following Introduction of Everolimus—Results of a Multicenter Trial
  • 2012
  • In: American Journal of Transplantation. - : Wiley-Blackwell. - 1600-6135 .- 1600-6143. ; 12:10, s. 2700-2709
  • Journal article (peer-reviewed)abstract
    • In this 12-month multicenter Scandinavian study, 78 maintenance heart transplant (HTx) recipients randomized to everolimus with reduced calcineurin inhibitor (CNI) exposure or continued standard CNI-therapy underwent matched virtual histology (VH) examination to evaluate morphological progression of cardiac allograft vasculopathy (CAV). Parallel measurement of a range of inflammatory markers was also performed. A similar rate of quantitative CAV progression was observed in the everolimus (n = 30) and standard CNI group (n = 48) (plaque index 1.9 +/- 3.8% and 1.6 +/- 3.9%, respectively; p = 0.65). However, VH analysis revealed a significant increase in calcified (2.4 +/- 4.0 vs. 0.3 +/- 3.1%; p = 0.02) and necrotic component (6.5 +/- 8.5 vs. 1.1 +/- 8.6%; p = 0.01) among everolimus patients compared to controls. The increase in necrotic and calcified components was most prominent in everolimus patients with time since HTx andgt;5.1 years and was accompanied by a significant increase in levels of von Willebrand (vWF) factor (p = 0.04) and vascular cell adhesion molecule (VCAM) (p = 0.03). Conversion to everolimus and reduced CNI is associated with a significant increase in calcified and necrotic intimal components and is more prominent in patients with a longer time since HTx. A significant increase in vWF and VCAM accompanied these qualitative changes and the prognostic implication of these findings requires further investigation.
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2.
  • Jansson, Daniel T., et al. (author)
  • Metabolism, inflammation and postoperative time are the key to early diagnosis of anastomotic leak
  • 2019
  • In: Journal of Surgery and Surgical Research. - : Peertechz Publications Private Limited. - 2455-2968. ; 5:2
  • Journal article (peer-reviewed)abstract
    • Objective: The aim of the study was to find laboratory samples for early diagnosis of anastomotic leak.Summary background data: Anastomotic leakage after rectal cancer surgery is a severe complication with high mortality. Outcome is highly dependent on early diagnosis.Methods: 29 patients were investigated postoperatively after having undergone low anterior resection due to cancer recti. Patient outcomes were divided into three groups: Anastomotic leak in 7 patients, other complications in 9 patients and 13 patients who were free of complications. Patients were monitored every 6th hour with blood and intraperitoneal samples in order to identify laboratory markers for early detection of anastomotic leakage. An anastomotic leak index was created, a scoring system where points count for values higher than reference values of CRP and interleukin 6 in blood and intraperitoneal lactate, lactate/pyruvate ratio and interleukin 6 were measured at 18, 24, 42 and 48 hours postoperatively.Results: Significant differences between groups were found regarding CRP, Interleukin 6, fibrinogen and D-dimer in blood. Intraperitoneal differences were found not only in lactate and lactate/pyruvate ratio measured by microdialysis, significant differences in interleukin 6, interleukin 10 and tumour necrosis factor-α could also be demonstrated between the groups. The anastomotic leak index had a sensitivity and specificity of 86% (p=0.0007).Conclusions: The most important factor was time after operation. No laboratory parameter in itself could predict an anastomotic leak but the anastomotic leak index was a useful tool in the monitoring and assessment of clinical outcome.Mini abstract: Patients with anastomotic leak after rectal surgery were monitored with higher intraperitoneal cytokines and lactate/pyruvate ratio. The results suggest intraperitoneal microdialysis combined with blood samples of CRP and IL 6 as a feasible method for early diagnosis of anastomotic leak.
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3.
  • Jansson, Kjell, 1958-, et al. (author)
  • Normal values and differences between intraperitoneal and subcutaneous microdialysis in patients after non‐complicated gastrointestinal surgery
  • 2005
  • In: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 65:4, s. 273-282
  • Journal article (peer-reviewed)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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4.
  • Malinovschi, Andrei, 1978-, et al. (author)
  • Assessment of Global Lung Function Initiative (GLI) reference equations for diffusing capacity in relation to respiratory burden in the Swedish CArdioPulmonary bioImage Study (SCAPIS)
  • 2020
  • In: European Respiratory Journal. - Lausanne, Switzerland : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 56:2
  • Journal article (peer-reviewed)abstract
    • The Global Lung Function Initiative (GLI) has recently published international reference values for diffusing capacity of the lung for carbon monoxide (DLCO). Lower limit of normal (LLN), i.e. the 5th percentile, usually defines impaired DLCO. We examined if the GLI LLN for DLCO differs from the LLN in a Swedish population of healthy, never-smoking individuals and how any such differences affect identification of subjects with respiratory burden.Spirometry, DLCO, chest high-resolution computed tomography (HRCT) and questionnaires were obtained from the first 15 040 participants, aged 50–64 years, of the Swedish CArdioPulmonary bioImage Study (SCAPIS). Both GLI reference values and the lambda-mu-sigma (LMS) method were used to define the LLN in asymptomatic never-smokers without respiratory disease (n=4903, of which 2329 were women).Both the median and LLN for DLCO from SCAPIS were above the median and LLN from the GLI (p<0.05). The prevalence of DLCO DLCO >GLI LLN but DLCO >GLI LLN but versus 4.5%, p<0.001), chronic airflow limitation (8.5% versus 3.9%, p<0.001) and chronic bronchitis (8.3% versus 4.4%, p<0.01) than subjects (n=13 600) with normal DLCO (>GLI LLN and >SCAPIS LLN). No differences were found with regard to physician-diagnosed asthma.The GLI LLN for DLCO is lower than the estimated LLN in healthy, never-smoking, middle-aged Swedish adults. Individuals with DLCO above the GLI LLN but below the SCAPIS LLN had, to a larger extent, an increased respiratory burden. This suggests clinical implications for choosing an adequate LLN for studied populations.
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6.
  • Oikonomakis, Ioannis, 1977-, et al. (author)
  • Fully covered self-expandable metal stent placed over a stapled colon anastomosis in an animal model: A pilot study of colon metabolism over the stent
  • 2022
  • In: Jgh Open. - : Wiley. - 2397-9070. ; 6:5, s. 338-343
  • Journal article (peer-reviewed)abstract
    • Background and Aim: Anastomotic leakage (AL) in colorectal resection and primary anastomosis is a common and feared complication. Fully covered self-expandable metal stents (FCSEMSs) have been used for the treatment of AL. It is still unknown whether FCSEMSs affect anastomosis healing negatively by causing ischemia. In an animal study, we investigated the metabolic effects over a FCSEMS covering a stapled colon anastomosis. Methods: Seven pigs were investigated using microdialysis after laparotomy, colon resection, and anastomosis with stent placement. Measurements were done at the proximal and distal ends of the anastomosis and at a reference catheter placed at the small intestine. Measurements of glucose, pyruvate, lactate, glycerol, and the lactate/ pyruvate ratio (L/P) were carried out. Results: Lactate and L/P were significantly higher at the oral part of the anastomosis, while glucose showed a small declining tendency. At the distal part of the anastomosis, glucose decreased significantly after the resection but did not reach zero. Lactate increased significantly whereas L/P increased only slightly. Glycerol levels were stable. Conclusion: Colon resection caused initially hypermetabolism in the intestinal ends next to the resection site. This hypermetabolism neither deteriorated nor turned into ischemia during the initial postoperative course, but the start of hypoxemia could not be excluded during the study and after the placement of an FCSEMS.
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7.
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8.
  • Alshamari, Muhammed, 1975-, et al. (author)
  • Diagnostic accuracy of low-dose CT compared with abdominal radiography in non-traumatic acute abdominal pain : prospective study and systematic review
  • 2016
  • In: European Radiology. - New York : Springer. - 0938-7994 .- 1432-1084. ; 26:6, s. 1766-1774
  • Research review (peer-reviewed)abstract
    • Objectives: Abdominal radiography is frequently used in acute abdominal non-traumatic pain despite the availability of more advanced diagnostic modalities. This study evaluates the diagnostic accuracy of low-dose CT compared with abdominal radiography, at similar radiation dose levels.Methods: Fifty-eight patients were imaged with both methods and were reviewed independently by three radiologists. The reference standard was obtained from the diagnosis in medical records. Sensitivity and specificity were calculated. A systematic review was performed after a literature search, finding a total of six relevant studies including the present.Results: Overall sensitivity with 95 % CI for CT was 75 % (66-83 %) and 46 % (37-56 %) for radiography. Specificity was 87 % (77-94 %) for both methods. In the systematic review the overall sensitivity for CT varied between 75 and 96 % with specificity from 83 to 95 % while the overall sensitivity for abdominal radiography varied between 30 and 77 % with specificity 75 to 88 %.Conclusions: Based on the current study and available evidence, low-dose CT has higher diagnostic accuracy than abdominal radiography and it should, where logistically possible, replace abdominal radiography in the workup of adult patients with acute non-traumatic abdominal pain.Key points: • Low-dose CT has a higher diagnostic accuracy than radiography. • A systematic review shows that CT has better diagnostic accuracy than radiography. • Radiography has no place in the workup of acute non-traumatic abdominal pain.
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9.
  • Andreassen, A. K., et al. (author)
  • Everolimus Initiation and Early Calcineurin Inhibitor Withdrawal in Heart Transplant Recipients: A Randomized Trial
  • 2014
  • In: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 14:8, s. 1828-1838
  • Journal article (peer-reviewed)abstract
    • In a randomized, open-label trial, everolimus was compared to cyclosporine in 115 de novo heart transplant recipients. Patients were assigned within 5 days posttransplant to low-exposure everolimus (3-6 ng/mL) with reduced-exposure cyclosporine (n 56), or standard-exposure cyclosporine (n = 59), with both mycophenolate mofetil and corticosteroids. In the everolimus group, cyclosporine was withdrawn after 7-11 weeks and everolimus exposure increased (6-10 ng/mL). The primary efficacy end point, measured GFR at 12 months posttransplant, was significantly higher with everolimus versus cyclosporine (mean +/- SD: 79.8 +/- 17.7 mL/min/1.73m 2 vs. 61.5 +/- 19.6 mL/min/1.73m 2; p<0.001). Coronary intravascular ultrasound showed that the mean increase in maximal intimal thickness was smaller (0.03 mm [95% CI 0.01, 0.05 mm] vs. 0.08 mm [95% CI 0.05, 0.12 mm], p = 0.03), and the incidence of cardiac allograft vasculopathy (CAV) was lower (50.0% vs. 64.6%, p = 0.003), with everolimus versus cyclosporine at month 12. Biopsy-proven acute rejection after weeks 7-11 was more frequent with everolimus (p = 0.03). Left ventricular function was not inferior with everolimus versus cyclosporine. Cytomegalovirus infection was less common with everolimus (5.4% vs. 30.5%, p<0.001); the incidence of bacterial infection was similar. In conclusion, everolimus-based immunosuppression with early elimination of cyclosporine markedly improved renal function after heart transplantation. Since postoperative safety was not jeopardized and development of CAV was attenuated, this strategy may benefit long-term outcome.
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10.
  • Andreassen, A. K., et al. (author)
  • Everolimus Initiation With Early Calcineurin Inhibitor Withdrawal in De Novo Heart Transplant Recipients: Three-Year Results From the Randomized SCHEDULE Study
  • 2016
  • In: American Journal of Transplantation. - : WILEY-BLACKWELL. - 1600-6135 .- 1600-6143. ; 16:4, s. 1238-1247
  • Journal article (peer-reviewed)abstract
    • In a randomized, open-label trial, de novo heart transplant recipients were randomized to everolimus (3-6ng/mL) with reduced-exposure calcineurin inhibitor (CNI; cyclosporine) to weeks 7-11 after transplant, followed by increased everolimus exposure (target 6-10ng/mL) with cyclosporine withdrawal or standard-exposure cyclosporine. All patients received mycophenolate mofetil and corticosteroids. A total of 110 of 115 patients completed the 12-month study, and 102 attended a follow-up visit at month 36. Mean measured GFR (mGFR) at month 36 was 77.4mL/min (standard deviation [SD] 20.2mL/min) versus 59.2mL/min (SD 17.4mL/min) in the everolimus and CNI groups, respectively, a difference of 18.3mL/min (95% CI 11.1-25.6mL/min; p < 0.001) in the intention to treat population. Multivariate analysis showed treatment to be an independent determinant of mGFR at month 36. Coronary intravascular ultrasound at 36 months revealed significantly reduced progression of allograft vasculopathy in the everolimus group compared with the CNI group. Biopsy-proven acute rejection grade 2R occurred in 10.2% and 5.9% of everolimus- and CNI-treated patients, respectively, during months 12-36. Serious adverse events occurred in 37.3% and 19.6% of everolimus- and CNI-treated patients, respectively (p=0.078). These results suggest that early CNI withdrawal after heart transplantation supported by everolimus, mycophenolic acid and steroids with lymphocyte-depleting induction is safe at intermediate follow-up. This regimen, used selectively, may offer adequate immunosuppressive potency with a sustained renal advantage. A follow-up study of the SCHEDULE trial, which randomized de novo heart transplant recipients to everolimus with cyclosporine discontinuation or to standard-exposure cyclosporine, shows that measured glomerular filtration rate remains significantly higher in the everolimus group at three years posttransplant, with significantly reduced progression of allograft vasculopathy compared to cyclosporine therapy.
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Jansson, Kjell (153)
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