| 1. |
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| 2. |
- Ludvigsson, Johnny, et al.
(författare)
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GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus
- 2012
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 366:5, s. 433-442
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes.METHODS: We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixed-meal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels.RESULTS: The stimulated C-peptide level declined to a similar degree in all study groups, and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group (P=0.10). The use of GAD-alum as compared with placebo did not affect the insulin dose, glycated hemoglobin level, or hypoglycemia rate. Adverse events were infrequent and mild in the three groups, with no significant differences.CONCLUSIONS: Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period.
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| 3. |
- Alriksson, Stina, 1971-
(författare)
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Environmental preferences among steel stakeholders
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Emissions of carbon dioxide, dioxins, nitrogen oxides and particulate matter as well as use of non-renewable resources and energy are some important sustainability challenges for the Swedish steel industry. Much effort has been made, mainly by technical solutions, which to a high degree have decreased the emissions during the last 30 years.Technical solutions however will not be sufficient to reach sustainable development, stakeholder involvement is also necessary. Stakeholder theory states that stakeholder involvement must include a dialog between the stakeholders involved and the operation. The first step in this process is to identify which key issues the stakeholders find most important and then the organisation needs to start interact with its stakeholders. This thesis deals with such issues.Stakeholder preferences for environmental issues were assessed with conjoint analysis, Q-methodology and focus group discussions. The theory of planned behaviour was used to assess how attitudes were connected to background factors and a potential pro-environmental behaviour.Five studies have been carried out in the framework of this thesis. The studies include: a literature review, method evaluation, evaluation of environmental objectives in stakeholder groups, screening of relevant factors, evaluation of steel environmental characteristics, identification of barriers to the introduction of new materials and the impact of worry and risk perception on strategic environmental decisions.It can be concluded that the methods applied in the studies work well in eliciting preferences. It has been possible to show how different stakeholder groups as well as individuals prioritise environmental objectives and sustainability issues. Since individuals within a stakeholder group vary considerably in preferences, the results from this thesis show the importance of illustrating results on an individual level instead of the traditional group level. Also, a method has been tested where the results were brought back to the respondents in order to stimulate discussions between different stakeholder groups.
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| 4. |
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| 5. |
- Böhnke, Tobias, et al.
(författare)
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Surfaces with high solar reflectance and high thermal emittance on structured silicon for spacecraft thermal control
- 2008
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Ingår i: Optical materials (Amsterdam). - : Elsevier BV. - 0925-3467 .- 1873-1252. ; 30:9, s. 1410-1421
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Tidskriftsartikel (refereegranskat)abstract
- Presented here is an examination of unstructured and structured (by anisotropic etching), monocrystalline silicon wafers coated with sputter deposited aluminum and chemical vapor deposited silicon dioxide for high solar reflectance and high thermal emittance, respectively. The topography of the samples was characterized with optical and scanning electron microscopy. Optical properties were examined with reflectance and transmittance spectroscopy, partly by usage of an integrating sphere. The measurement results were used to estimate the equilibrium temperature of the surfaces in space. The suitability of the surfaces with high solar reflectance and high thermal emittance to aid in the thermal control of miniaturized, highly integrated components for space applications is discussed. A silicon dioxide layer on a metal layer results in a slightly lower reflectance when compared to surfaces with only a metal layer, but might be beneficial for miniaturized space components and modules that have to dissipate internally generated heat into open space. Additionally, it is an advantage to microstructure the emitting surface for enhanced radiation of excess heat.
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| 6. |
- Dahlgren, David, et al.
(författare)
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Direct In Vivo Human Intestinal Permeability (P-eff) Determined with Different Clinical Perfusion and Intubation Methods
- 2015
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 104:9, s. 2702-2726
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Forskningsöversikt (refereegranskat)abstract
- Regional in vivo human intestinal effective permeability (P-eff) is calculated by measuring the disappearance rate of substances during intestinal perfusion. P-eff is the most relevant parameter in the prediction of rate and extent of drug absorption from all parts of the intestine. Today, human intestinal perfusions are not performed on a routine basis in drug development. Therefore, it would be beneficial to increase the accuracy of the in vitro and in silico tools used to evaluate the intestinal P-eff of novel drugs. This review compiles historical P-eff data from 273 individual measurements of 80 substances from 61 studies performed in all parts of the human intestinal tract. These substances include: drugs, monosaccharaides, amino acids, dipeptides, vitamins, steroids, bile acids, ions, fatty acids, and water. The review also discusses the determination and prediction of P-eff using in vitro and in silico methods such as quantitative structure-activity relationship, Caco-2, Ussing chamber, animal intestinal perfusion, and physiologically based pharmacokinetic (PBPK) modeling. Finally, we briefly outline how to acquire accurate human intestinal P-eff data by deconvolution of plasma concentration-time profiles following regional intestinal bolus dosing.
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| 7. |
- Dahlgren, David, et al.
(författare)
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Effect of absorption-modifying excipients, hypotonicity, and enteric neural activity in an in vivo model for small intestinal transport.
- 2018
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 549:1-2, s. 239-248
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Tidskriftsartikel (refereegranskat)abstract
- The small intestine mucosal barrier is physiologically regulated by the luminal conditions, where intestinal factors, such as diet and luminal tonicity, can affect mucosal permeability. The intestinal barrier may also be affected by absorption-modifying excipients (AME) in oral drug delivery systems. Currently, there is a gap in the understanding of how AMEs interact with the physiological regulation of intestinal electrolyte transport and fluid flux, and epithelial permeability. Therefore, the objective of this single-pass perfusion study in rat was to investigate the effect of three AMEs on the intestinal mucosal permeability at different luminal tonicities (100, 170, and 290 mOsm). The effect was also evaluated following luminal administration of a nicotinic receptor antagonist, mecamylamine, and after intravenous administration of a COX-2 inhibitor, parecoxib, both of which affect the enteric neural activity involved in physiological regulation of intestinal functions. The effect was evaluated by changes in intestinal lumen-to-blood transport of six model compounds, and blood-to-lumen clearance of 51Cr-EDTA (a mucosal barrier marker). Luminal hypotonicity alone increased the intestinal epithelial transport of 51Cr-EDTA. This effect was potentiated by two AMEs (SDS and caprate) and by parecoxib, while it was reduced by mecamylamine. Consequently, the impact of enteric neural activity and luminal conditions may affect nonclinical determinations of intestinal permeability. In vivo predictions based on animal intestinal perfusion models can be improved by considering these effects. The in vivo relevance can be increased by treating rats with a COX-2 inhibitor prior to surgery. This decreases the risk of surgery-induced ileus, which may affect the physiological regulation of mucosal permeability.
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| 8. |
- Dahlgren, David, et al.
(författare)
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Evaluation of drug permeability calculation based on luminal disappearance and plasma appearance in the rat single-pass intestinal perfusion model
- 2019
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 142, s. 31-37
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Tidskriftsartikel (refereegranskat)abstract
- The rat single-pass intestinal perfusion (SPIP) model is commonly used to investigate gastrointestinal physiology and membrane drug transport. The SPIP model can be used with the intestinal segment inside or outside the abdomen. The rats can also be treated with parecoxib, a selective cycloxygenase-2 inhibitor that has been shown to affect some intestinal functions following abdominal surgery, such as motility, epithelial permeability, fluid flux and ion transport. However, the impact of extra-abdominal placement of the intestinal segment in combination with parecoxib on intestinal drug transport has not been investigated. There is also uncertainty how well intestinal permeability determinations based on luminal drug disappearance and plasma appearance correlate in the rat SPIP model. The main objective of this rat in vivo study was to investigate the effect of intra- vs. extra abdominal SPIP, with and without, pretreatment with parecoxib. The effect was evaluated by determining the difference in blood-to-lumen Cr-51-EDTA clearance, lumen-to-blood permeability of a cassette-dose of four model compounds (atenolol, enalaprilat, ketoprofen, and metoprolol), and water flux. The second objective was to compare the jejunal permeability values of the model drugs when determined based on luminal disappearance or plasma appearance. The study showed that the placement of the perfused jejunal segment, or the treatment with parecoxib, had minimal effects on membrane permeability and water flux. It was also shown that intestinal permeability of low permeability compounds should be determined on the basis of data from plasma appearance rather than lumina] disappearance. If permeability is calculated on the basis of luminal disappearance, it should preferably include negative values to increase the accuracy in the determinations.
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| 9. |
- Dahlgren, David, et al.
(författare)
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Preclinical Effect of Absorption Modifying Excipients on Rat Intestinal Transport of Model Compounds and the Mucosal Barrier Marker 51Cr-EDTA
- 2017
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 14:12, s. 4243-4251
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Tidskriftsartikel (refereegranskat)abstract
- There is a renewed interest from the pharmaceutical field to develop oral formulations of compounds, such as peptides, oligonucleotides, and polar drugs. However, these often suffer from insufficient absorption across the intestinal mucosal barrier. One approach to circumvent this problem is the use of absorption modifying excipient(s) (AME). This study determined the absorption enhancing effect of four AMEs (sodium dodecyl sulfate, caprate, chitosan, N-acetylcysteine) on five model compounds in a rat jejunal perfusion model. The aim was to correlate the model compound absorption to the blood-to-lumen clearance of the mucosal marker for barrier integrity, 51Cr-EDTA. Sodium dodecyl sulfate and chitosan increased the absorption of the low permeation compounds but had no effect on the high permeation compound, ketoprofen. Caprate and N-acetylcysteine did not affect the absorption of any of the model compounds. The increase in absorption of the model compounds was highly correlated to an increased blood-to-lumen clearance of 51Cr-EDTA, independent of the AME. Thus, 51Cr-EDTA could be used as a general, sensitive, and validated marker molecule for absorption enhancement when developing novel formulations.
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| 10. |
- Dahlgren, David, et al.
(författare)
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Regional Intestinal Permeability in Dogs : Biopharmaceutical Aspects for Development of Oral Modified-Release Dosage Forms
- 2016
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 13:9, s. 3022-3033
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Tidskriftsartikel (refereegranskat)abstract
- The development of oral modified-release (MR) dosage forms requires an active pharmaceutical ingredient (API) with a sufficiently high absorption rate in both the small and large intestine. Dogs are commonly used in preclinical evaluation of regional intestinal absorption and in the development of novel MR dosage forms. This study determined regional intestinal effective permeability (P-eff) in dogs with the aim to improve regional Peff prediction in humans. Four model drugs, atenolol, enalaprilat, metoprolol, and ketoprofen, were intravenously and regionally dosed twice as a solution into the proximal small intestine (P-SI) and large intestine (LI) of three dogs with intestinal stomas. Based on plasma data from two separate study occasions for each dog, regional Peff values were calculated using a validated intestinal deconvolution method. The determined mean P-eff values were 0.62, 0.14, 1.06, and 3.66 X 10(-4) cm/s in the P-SI, and 0.13, 0.02, 1.03, and 2.20 X 10(-4) cm/s in the LI, for atenolol, enalaprilat, metoprolol, and ketoprofen, respectively. The determined P-SI Peff values in dog were highly correlated (R-2 = 0.98) to the historically directly determined human jejunal P-eff after a single-pass perfusion. The determined dog P-SI P-eff values were also successfully implemented in GI-Sim to predict the risk for overestimation of LI absorption of low permeability drugs. We conclude that the dog intestinal stoma model is a useful preclinical tool for determination of regional intestinal permeability. Still, further studies are recommended to evaluate additional APIs, sources of variability, and formulation types, for more accurate determination of the dog model in the drug development process.
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| 11. |
- Dahlgren, David, et al.
(författare)
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Regional Intestinal Permeability of Three Model Drugs in Human
- 2016
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 13:9, s. 3013-3021
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Tidskriftsartikel (refereegranskat)abstract
- Currently there are only a limited number of determinations of human P-eff in the distal small intestine and none in the large intestine. This has hindered the validation of preclinical models with regard to absorption in the distal parts of the intestinal tract, which can be substantial for BCS class II-IV drugs, and drugs formulated into modified-release (MR) dosage forms. To meet this demand, three model drugs (atenolol, metoprolol, and ketoprofen) were dosed in solution intravenously, and into the jejunum, ileum, and colon of 14 healthy volunteers. The P-eff of each model drug was then calculated using a validated deconvolution method. The median P-eff of atenolol in the jejunum, ileum, and colon was 0.45, 0.15, and 0.013 X 10(-4) cm/s, respectively. The corresponding values for metoprolol were 1.72, 0.72, and 1.30 X 10(-4) cm/s, and for ketoprofen 8.85, 6.53, and 3.37 X 10(-4) cm/s, respectively. This is the first study where the human Peff of model drugs has been determined in all parts of the human intestinal tract in the same subjects. The jejunal values were similar to directly determined values using intestinal single-pass perfusion, indicating that the deconvolution method is a valid approach for determining regional P-eff. The values from this study will be highly useful in the validation of preclinical regional absorption models and in silico tools.
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| 12. |
- Dahlgren, David, et al.
(författare)
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The effects of three absorption-modifying critical excipients on the in vivo intestinal absorption of six model compounds in rats and dogs.
- 2018
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 547:1-2, s. 158-168
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Tidskriftsartikel (refereegranskat)abstract
- Pharmaceutical excipients that may affect gastrointestinal (GI) drug absorption are called critical pharmaceutical excipients, or absorption-modifying excipients (AMEs) if they act by altering the integrity of the intestinal epithelial cell membrane. Some of these excipients increase intestinal permeability, and subsequently the absorption and bioavailability of the drug. This could have implications for both the assessment of bioequivalence and the efficacy of the absorption-enhancing drug delivery system. The absorption-enhancing effects of AMEs with different mechanisms (chitosan, sodium caprate, sodium dodecyl sulfate (SDS)) have previously been evaluated in the rat single-pass intestinal perfusion (SPIP) model. However, it remains unclear whether these SPIP data are predictive in a more in vivo like model. The same excipients were in this study evaluated in rat and dog intraintestinal bolus models. SDS and chitosan did exert an absorption-enhancing effect in both bolus models, but the effect was substantially lower than those observed in the rat SPIP model. This illustrates the complexity of the AME effects, and indicates that additional GI physiological factors need to be considered in their evaluation. We therefore recommend that AME evaluations obtained in transit-independent, preclinical permeability models (e.g. Ussing, SPIP) should be verified in animal models better able to predict in vivo relevant GI effects, at multiple excipient concentrations.
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| 13. |
- Dahlgren, David, et al.
(författare)
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Time-dependent effects on small intestinal transport by absorption-modifying excipients
- 2018
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 132, s. 19-28
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Tidskriftsartikel (refereegranskat)abstract
- The relevance of the rat single-pass intestinal perfusion model for investigating in vivo time-dependent effects of absorption-modifying excipients (AMEs) is not fully established. Therefore, the dynamic effect and recovery of the intestinal mucosa was evaluated based on the lumen-to-blood flux (Jabs) of six model compounds, and the blood-to-lumen clearance of 51Cr-EDTA (CLCr), during and after 15- and 60-min mucosal exposure of the AMEs, sodium dodecyl sulfate (SDS) and chitosan, in separate experiments. The contribution of enteric neurons on the effect of SDS and chitosan was also evaluated by luminal coadministration of the nicotinic receptor antagonist, mecamylamine. The increases in Jabs and CLCr (maximum and total) during the perfusion experiments were dependent on exposure time (15 and 60 min), and the concentration of SDS, but not chitosan. The increases in Jabs and CLCr following the 15-min intestinal exposure of both SDS and chitosan were greater than those reported from an in vivo rat intraintestinal bolus model. However, the effect in the bolus model could be predicted from the increase of Jabs at the end of the 15-min exposure period, where a six-fold increase in Jabs was required for a corresponding effect in the in vivo bolus model. This illustrates that a rapid and robust effect of the AME is crucial to increase the in vivo intestinal absorption rate before the yet unabsorbed drug in lumen has been transported distally in the intestine. Further, the recovery of the intestinal mucosa was complete following 15-min exposures of SDS and chitosan, but it only recovered 50% after the 60-min intestinal exposures. Our study also showed that the luminal exposure of AMEs affected the absorptive model drug transport more than the excretion of 51Cr-EDTA, as Jabs for the drugs was more sensitive than CLCr at detecting dynamic mucosal AME effects, such as response rate and recovery. Finally, there appears to be no nicotinergic neural contribution to the absorption-enhancing effect of SDS and chitosan, as luminal administration of 0.1 mM mecamylamine had no effect.
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| 14. |
- Forner, Kristin, et al.
(författare)
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Optimization of the Ussing chamber setup with excised rat intestinal segments for dissolution/permeation experiments of poorly soluble drugs
- 2017
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Ingår i: Drug Development and Industrial Pharmacy. - : TAYLOR & FRANCIS LTD. - 0363-9045 .- 1520-5762. ; 43:2, s. 338-346
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Tidskriftsartikel (refereegranskat)abstract
- Context: Prediction of the in vivo absorption of poorly soluble drugs may require simultaneous dissolution/permeation experiments. In vivo predictive media have been modified for permeation experiments with Caco-2 cells, but not for excised rat intestinal segments. Objective: The present study aimed at improving the setup of dissolution/permeation experiments with excised rat intestinal segments by assessing suitable donor and receiver media. Methods: The regional compatibility of rat intestine in Ussing chambers with modified Fasted and Fed State Simulated Intestinal Fluids (Fa/FeSSIFmod) as donor media was evaluated via several parameters that reflect the viability of the excised intestinal segments. Receiver media that establish sink conditions were investigated for their foaming potential and toxicity. Dissolution/permeation experiments with the optimized conditions were then tested for two particle sizes of the BCS class II drug aprepitant. Results: Fa/FeSSIFmod were toxic for excised rat ileal sheets but not duodenal sheets, the compatibility with jejunal segments depended on the bile salt concentration. A non-foaming receiver medium containing bovine serum albumin (BSA) and Antifoam B was nontoxic. With these conditions, the permeation of nanosized aprepitant was higher than of the unmilled drug formulations. Discussion: The compatibility of Fa/FeSSIFmod depends on the excised intestinal region. The chosen conditions enable dissolution/permeation experiments with excised rat duodenal segments. The experiments correctly predicted the superior permeation of nanosized over unmilled aprepitant that is observed in vivo. Conclusion: The optimized setup uses FaSSIF(mod) as donor medium, excised rat duodenal sheets as permeation membrane and a receiver medium containing BSA and Antifoam B.
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| 15. |
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| 16. |
- Gdaniec, Sandra, 1988-
(författare)
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231Pa and Th isotopes as tracers of deep water ventilation and scavenging in the Mediterranean Sea
- 2017
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The naturally occurring isotopes 231Pa and 230Th are used as tracers of marine biogeochemical processes. They are both produced from the radioactive decay of their uniformly distributed uranium parents (235U and 234U) in seawater. After production, 231Pa and 230Th are removed by adsorption onto settling particles (scavenging) and subsequently buried in marine sediments. 230Th is more particle reactive compared to 231Pa. Consequently, 230Th will be removed from the open ocean by adsorption onto settling particles, while 231Pa tend to be laterally transported by currents and removed by scavenging in areas of high particle flux (e.g. ocean margins). The primordial 232Th indicates lithogenic supply via rivers and resuspension of sediments, which provides additional information about processes involved in the cycling of particle reactive elements in the ocean. The preferential deposition of particle reactive elements at ocean margins (boundary scavenging) has important implications for our understanding of the distribution and dispersion of micronutrients (e.g. iron) and pollutants in the ocean. It is therefore valuable to understand the nature of boundary scavenging processes in order to evaluate the relative contribution of circulation and scavenging behaviors.The major characteristics of thermohaline circulation in the Mediterranean are well known and have been studied for decades. This sea is an almost land-locked area, where limited water-exchange with the Atlantic Ocean only occurs through the Strait of Gibraltar. Therefore, this marginal sea is often referred to as a “miniature ocean” suitable as a “laboratory” for marine environmental research. In this licentiate thesis, distributions of 231Pa, 230Th and 232Th in seawater and marine particles collected during the GEOTRACES MedSeA-GA04-S cruise in 2013 are presented. Observed nuclide distributions indicate the impact of deep water formation processes, where observed differences can be linked to the type of deep water formation process that occurs in respective basin. Essentially all in-situ produced 230Th is buried in Mediterranean Sea sediments. Despite lower affinity of 231Pa for marine particles, most 231Pa is also scavenged and deposited in Mediterranean Sea sediments. The efficient scavenging of 231Pa produces a relatively low fractionation between 231Pa and 230Th in terms of the fractionation factor FTh/Pa. This licentiate thesis presents a summary of the methods used for the analysis of 231Pa and Th-isotopes with details on the exchange chromatography method and the treatment of mass spectrometric data. The study of 231Pa, 230Th and 232Th in the Mediterranean Sea has important implications for our understanding of processes that control their water column distributions and how their behavior can be utilized to trace chemical flux in modern and past ocean environments.
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| 17. |
- Hammo, Sari, et al.
(författare)
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Outcome After Endovascular Repair of Ruptured Descending Thoracic Aortic Aneurysm : A National Multicentre Study
- 2019
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Saunders Elsevier. - 1078-5884 .- 1532-2165. ; 57:6, s. 788-794
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The purpose of this multicentre study was to analyse the outcome of thoracic endovascular aortic repair (TEVAR) in patients with ruptured descending thoracic aortic aneurysm (rDTAA).Methods: This is a nationwide retrospective study including all patients who underwent TEVAR for rDTAA at six major vascular university centres in Sweden between January 2000 and December 2015. Outcome measures were analysed using Kaplan-Meier estimator and multivariable Cox regression.Results: There were 140 patients (age [mean +/- SD] 74.1 +/- 8.8 years; 56% men; aneurysm size 64.8 +/- 19 mm), with rDTAA. In 53 patients (37.9%), the left subclavian artery was covered, and in 25 patients (17.9%) arch vessel revascularisation was performed. In total, 61/136 patients (45%) had a major complication within 30 days post TEVAR. Stroke (n = 20; 14.7%) was the most common complication, followed by paraplegia (n = 13; 9.6%) and major bleeding (n = 13; 9.6%). TEVAR related complications during follow up included endoleaks 22.1% (30/136; 14 type 1a, six type 1b, 10 not defined). In total, re-interventions (n = 31) were required in 27/137 (19.7%) patients. The median follow up time was 17.0 months (range 0-132 months). The Kaplan-Meier estimated survival was 80.0% at one month, 71.7% at three months, 65.3% at one year, 45.9% at three years, and 31.9% at five years. Age (HR 1.03; 95% CI 1.00-1.07; p = .046), history of stroke (HR 2.35; 95% CI 1.194.63; p = .014), previous aortic surgery (HR 2.11; 95% CI 1.15-3.87; p = .016) as well as post-operative major bleeding (HR 4.40; 95% CI 2.20-8.81; p = .001), stroke (HR 2.63; 95% CI 1.37-5.03; p = .004), and renal failure (HR 8.25; 95% CI 2.69-25.35; p = .001) were all associated with mortality.Conclusions: This nationwide multicentre study of patients with rDTAA undergoing TEVAR showed acceptable short- but poor long-term survival. Adequate proximal and distal aortic sealing zones are important for technical success. High risk patients and post-operative complications need to be further addressed in an effort to improve outcome.
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| 18. |
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| 19. |
- Hobro, Sture, et al.
(författare)
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Dialysis as a Novel Adjuvant Treatment for Malignant Cancers
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:20
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Forskningsöversikt (refereegranskat)abstract
- Cancer metabolism is characterized by an increased utilization of fermentable fuels, such as glucose and glutamine, which support cancer cell survival by increasing resistance to both oxidative stress and the inherent immune system in humans. Dialysis has the power to shift the patient from a state dependent on glucose and glutamine to a ketogenic condition (KC) combined with low glutamine levels—thereby forcing ATP production through the Krebs cycle. By the force of dialysis, the cancer cells will be deprived of their preferred fermentable fuels, disrupting major metabolic pathways important for the ability of the cancer cells to survive. Dialysis has the potential to reduce glucose levels below physiological levels, concurrently increase blood ketone body levels and reduce glutamine levels, which may further reinforce the impact of the KC. Importantly, ketones also induce epigenetic changes imposed by histone deacetylates (HDAC) activity (Class I and Class IIa) known to play an important role in cancer metabolism. Thus, dialysis could be an impactful and safe adjuvant treatment, sensitizing cancer cells to traditional cancer treatments (TCTs), potentially making these significantly more efficient.
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| 20. |
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| 21. |
- Johansson, Bertil, et al.
(författare)
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Granulocytic sarcomas in body cavities in childhood acute myeloid leukemias with 11q23/MLL rearrangements
- 2000
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Ingår i: Genes, Chromosomes and Cancer. - 1045-2257. ; 27:2, s. 136-142
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Tidskriftsartikel (refereegranskat)abstract
- Three childhood acute monoblastic leukemias (AML M5) with granulocytic sarcomas (GSs) are described. All displayed 11q23/MLL abnormalities, t(9;11)(p22;q23) in two cases and t(11;17)(q23;q21) in one case, constituting around 20% of all 11q23-positive AML cytogenetically investigated in our department. Two of the patients had GS in multiple locations, and all three had abdominal GS. In two of them, t(9;11)-positive GS was diagnosed prior to the diagnosis of AML. Fourteen (1.9%) of 752 published AML cases with 11q23 aberrations have had GS, either as a presenting feature or during disease progression. The incidence of GS has varied significantly (P < 0.05) between children (3.8%) and adults (0.8%). The most common AML subtype has been AML M5 ( approximately 75%) and the most frequent GS sites have been the skin, abdomen, orbit, and thorax. Considering the possibility of underreporting of GS in published cases and the relatively high frequency in our own series, we believe that 11q23/MLL rearrangements may predispose to GS development. Although extramedullary infiltrates in the skin are known to be frequent in cases of AML M5, which is often associated with 11q23 aberrations, the present findings indicate that GS in the abdomen, orbit, and thorax may also be common, especially in pediatric AML. Thus, the possibility of 11q23/MLL-positive GS should be suspected when tumors of uncertain derivation occur in these sites. Finally, the identification of 11q23/MLL abnormalities in GSs in two patients without overt AML underscores the importance of using cytogenetic and molecular genetic investigations as a diagnostic approach in the evaluation of tumorous lesions of unknown origin.
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| 22. |
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| 23. |
- Neuman, Paul, et al.
(författare)
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Longitudinal assessment of femoral knee cartilage quality using contrast enhanced MRI (dGEMRIC) in patients with anterior cruciate ligament injury - comparison with asymptomatic volunteers.
- 2011
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 19, s. 977-983
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In this observational longitudinal study we estimate knee joint cartilage glycosaminoglycan (GAG) content, in patients with an acute anterior cruciate ligament (ACL) injury, with or without a concomitant meniscus injury. METHODS: 29 knees (19 men/10 women) were prospectively examined by repeat delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), approximately 3 weeks and 2.3±1.3 (range 4.5) years after the injury. We estimated the GAG content (T1Gd) in the central weight-bearing parts of the medial and lateral femoral cartilage and compared results with a reference cohort (n=24) with normal knees and no history of injury examined by dGEMRIC at one occasion previously. RESULTS: The healthy reference group had longer T1Gd values compared with the ACL-injured patients at follow-up both medially: 428±38 vs 363±61ms (P<0.0001) and laterally: 445±41 vs 396±48ms (P=0.0002). At follow-up T1Gd was lower in meniscectomized patients compared to those without a meniscectomy, both medially (-84ms, P=0.002) and laterally (-38ms, P=0.05). In the injured group, the medial femoral cartilage showed similar T1Gd at the two dGEMRIC investigations: 357±50 vs 363±61ms (P=0.57), whereas the lateral femoral cartilage T1Gd increased: 374±48 vs 396±48ms (P=0.04). CONCLUSIONS: The general decrease in cartilage T1Gd in ACL-injured patients compared with references provide evidence for structural matrix GAG changes that seem more pronounced if a concomitant meniscal injury is present. The fact that post-traumatic OA commonly develops in ACL-injured patients, in particularly those with meniscectomy, suggests that shorter T1Gd may be an early biomarker for OA.
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| 24. |
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| 25. |
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| 26. |
- Roos, Carl, et al.
(författare)
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Effects of absorption-modifying excipients on jejunal drug absorption in simulated fasted and fed luminal conditions
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - 0939-6411 .- 1873-3441.
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Tidskriftsartikel (refereegranskat)abstract
- The pharmaceutical industry, prescribers, and patients have all traditionally preferred oral administration of drug products. In recent years there has been an increase in drug candidates with low solubility and/or low permeability, which may limit the use of oral administration. To increase the possibility of oral administration for the poorly permeating drugs, the use of absorption modifying excipients (AMEs) has been proposed, with the aim of increasing the fraction of dose absorbed. The effects of AMEs have previously been investigated in various animal models, including the single-pass intestinal perfusion (SPIP) in rats. To further improve the biorelevance and the in vivo predictiveness of the SPIP model, four compounds (atenolol, enalaprilat, ketoprofen, metoprolol) were perfused in fasted or fed state simulated intestinal fluid (FaSSIF or FeSSIF) together with the AMEs N-acetyl-cysteine, caprate, or sodium dodecyl sulphate. For the poorly permeating compounds enalaprilat and atenolol, the flux was increased the most by the addition of SDS in both FaSSIF and FeSSIF. For ketoprofen, the flux decreased in the presence of all AMEs in at least one of the perfusion media. The flux of metoprolol was not affected by any of the excipients. The changes in magnitude in the compounds’ absorptions were in general smaller in FeSSIF than in FaSSIF, possibly due to differences in colloidal structures present in FeSSIF that made the AMEs less available. The results in FeSSIF were similar to those from bolus-dosing in rat, which further suggests that the effect of AMEs on permeability is strongly affected by interactions between AMEs and colloidal structures in the intestinal lumen. The results suggest that, when investigating the effects of AMEs, the biorelevance of the SPIP method can be increased by the addition of intraluminal constituents to the perfusate.
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| 27. |
- Roos, Carl, et al.
(författare)
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Effects of absorption-modifying excipients on jejunal drug absorption in simulated fasted and fed luminal conditions
- 2019
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 142, s. 387-395
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Tidskriftsartikel (refereegranskat)abstract
- Oral administration of drug products is the preferred administration route. In recent decades there has been an increase in drug candidates with low solubility and/or low permeability. To increase the possibility of oral administration for the poorly permeating drugs, the use of absorption modifying excipients (AMEs) has been proposed. These types of AMEs may also affect the regulatory assessment of a novel drug delivery system if they affect the absorption of a drug from any of the four BCS classes. The effects of AMEs have previously been investigated in various animal models, including the single-pass intestinal perfusion (SPIP) in rats. To further improve the biorelevance and the in vivo predictiveness of the SPIP model, four compounds (atenolol, enalaprilat, ketoprofen, metoprolol) were perfused in fasted or fed state simulated intestinal fluid (FaSSIF or FeSSIF) together with the AMEs N-acetyl-cysteine, caprate, or sodium dodecyl sulfate. For the highly soluble and poorly permeating compounds enalaprilat and atenolol (BCS class III), the flux was increased the most by the addition of SDS in both FaSSIF and FeSSIF. For ketoprofen (BCS class II), the flux decreased in the presence of all AMEs in at least one of the perfusion media. The flux of metoprolol (BCS class I) was not affected by any of the excipients in none of simulated prandial states. The changes in magnitude in the absorption of the compounds were in general smaller in FeSSIF than in FaSSIF. This may be explained by a reduced free concentration AMEs in FeSSIF. Further, the results in FeSSIF were similar to those from intrajejunal bolus administration in rat in a previous study. This suggests that the biorelevance of the SPIP method may be increased when investigating the effects of AMEs, by the addition of intraluminal constituents representative to fasted and/or fed state to the inlet perfusate.
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| 28. |
- Roos, Carl, et al.
(författare)
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In Vivo Mechanisms of Intestinal Drug Absorption from Aprepitant Nanoformulations
- 2017
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 14:12, s. 4233-4242
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Tidskriftsartikel (refereegranskat)abstract
- Over recent decades there has been an increase in the proportion of BCS class II and IV drug candidates in industrial drug development. To overcome the biopharmaceutical challenges associated with the less favorable properties of solubility and/or intestinal permeation of these substances, the development of formulations containing nanosuspensions of the drugs has been suggested. The intestinal absorption of aprepitant from two nanosuspensions (20 mu M and 200 mu M total concentrations) in phosphate buffer, one nanosuspension (200 mu M) in fasted-state simulated intestinal fluid (FaSSIF), and one solution (20 mu M) in FaSSIF was investigated in the rat single-pass intestinal perfusion model. The disappearance flux from the lumen (J(disapp)) was faster for formulations containing a total concentration of aprepitant of 200 mu M than for those containing 20 mu M, but was unaffected by the presence of vesicles. The flux into the systemic circulation (J(app)) and, subsequently, the effective diffusion constant (D-eff) were calculated using the plasma concentrations. J(app) was, like J(disapp), faster for the formulations containing higher total concentrations of aprepitant, but was also faster for those containing vesicles (ratios of 2 and 1.5). This suggests that aprepitant is retained in the lumen when presented as nanoparticles in the absence of vesicles. In conclusion, increased numbers of nanoparticles and the presence of vesicles increased the rate of transport and availability of aprepitant in plasma. This effect can be attributed to an increased rate of mass transport through the aqueous boundary layer (ABL) adjacent to the gut wall.
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| 29. |
- Roos, Camilla, et al.
(författare)
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Insulin resistance and self-rated symptoms of depression in Swedish women with risk factors for diabetes: the Women's Health in the Lund Area study.
- 2007
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Ingår i: Metabolism, Clinical and Experimental. - : Elsevier BV. - 1532-8600. ; 56:6, s. 825-829
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have suggested that depression increases the risk for diabetes and that this may be mediated through insulin resistance. The study aimed to analyze if self-rated symptoms of depression are related to insulin resistance among middle-aged and older Swedish women with features of the metabolic syndrome and being at risk for type 2 diabetes mellitus. We analyzed data from 1047 Swedish women aged 50 to 64 years without a history of diabetes and living in the southern part of Sweden. A variable self-rated symptoms of depression (SRSD) was defined by using the Gothenburg Quality of Life instrument. We estimated odds ratios (ORs) to determine whether or not SRSD was associated with the homeostasis model assessment of insulin resistance. The variable SRSD was not associated with insulin resistance. However, it was positively associated with waist-hip ratio (OR, 1.95; 95% confidence interval, 1.28-3.00) and negatively associated with physical exercise (OR, 1.29; 95% confidence interval, 0.99-1.68) after multivariate adjustment. In conclusion, lifestyle factors such as physical inactivity and abdominal obesity, but not insulin resistance, seem to be related to self-rated symptoms of depression in women with risk factors for diabetes mellitus. The relationship between insulin resistance and major depression needs to be further examined.
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| 30. |
- Roos, Carl
(författare)
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Intestinal absorption of drugs : The impact of regional permeability, nanoparticles, and absorption-modifying excipients
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- For successful delivery of orally given drug products, the drug compounds must have adequate solubility and permeability in the human gastrointestinal tract. The permeability of a compound is determined by its size and lipophilicity, and is usually evaluated in various pre-clinical models, including rat models.This thesis had three major aims: 1) investigate regional permeability in human and rat intestines and evaluate two different rat models, 2) investigate the mechanisms behind absorption in nanosuspensions, and 3) investigate the effect of food on the absorption of drug molecules in solutions and suspensions, and also food’s effect on absorption modifying excipients (AMEs).Effective human permeability values obtained using regional intra-intestinal dosing and a deconvolution method agreed with values established by perfusion from the jejunum, demonstrating the accuracy and validity of the intra-intestinal bolus-dosing approach. Single-pass intestinal perfusion (SPIP) in rats showed better correlation with human effective permeability than the Ussing chamber, and was therefore deemed the better model for predicting drug permeability in humans.Absorption of microsuspensions and nanosuspension was investigated using rat SPIP, which showed that microsuspensions are subject to pronounced food effects, probably by partitioning of drug into the colloidal structures formed by bile acids, lecithin, and fatty acids. Nanosuspensions were less affected by food, which was attributed to fewer available nanoparticles in the fed state due to partitioning into colloidal structures, and because nanoparticles are able to cross the aqueous boundary layer on their own, increasing the concentration of drug adjacent to the epithelial membrane.AMEs had less effect in the fed state than the fasted state when investigated using SPIP. This difference may be caused by AMEs partitioning into luminal colloidal structures, decreasing the AMEs’ effects on the intestinal membrane. It thus seems that AMEs as well as drug compounds are subject to food-drug interactions, which may either increase or decrease the effect or absorption, something that needs to be considered during development of new drug products. In summary, this thesis has improved the knowledge of pre-clinical absorption models and the understanding of several biopharmaceutical mechanisms important for drug absorption.
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| 31. |
- Roos, Carl, et al.
(författare)
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Jejunal absorption of aprepitant from nanosuspensions : Role of particle size, prandial state and mucus layer.
- 2018
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 132, s. 222-230
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Tidskriftsartikel (refereegranskat)abstract
- The number of highly lipophilic active pharmaceutical ingredients (APIs) in pharmaceutical development has been constantly increasing over recent decades. These APIs often have inherent issues with solubility and dissolution, limiting their oral bioavailability. Traditionally, a reduction in particle size to the micrometer range has been used to improve dissolution. More recently, size reduction to the nanometer range has been introduced, which further increases the dissolution rate, but may also involve other mechanisms for increasing bioavailability. The effect of particle size on the absorption of aprepitant was investigated using the single-pass intestinal perfusion (SPIP) model in the rat jejunum. Phosphate buffer, fasted-state simulated intestinal fluid (FaSSIF), and fed-state simulated intestinal fluid (FeSSIF) were used as perfusion media to increase understanding of the processes involved and the effects of colloidal structures. The role of mucus on intestinal absorption was investigated by adding the mucolytic agent N-acetyl-cysteine (NAC). The absorption of aprepitant from the nanosuspensions was similar with all perfusion media (buffer = FaSSIF = FeSSIF), whereas food had a pronounced effect on absorption from the microsuspensions (FeSSIF > FaSSIF > buffer). The colloidal structures hence contributed to absorption from the microsuspensions. Partitioning of aprepitant from the nanosuspension into the colloidal structures decreased the amount of nanoparticles available, which offset the effect of food. The appearance flux of aprepitant in blood was non-significantly decreased for nanosuspensions of aprepitant with NAC versus without NAC in buffer (ratio of 2:1), indicating that particle deposition in the mucus may have been decreased as the layer thinned, with subsequently reduced intestinal absorption. The study also showed that the SPIP model is suitable for investigating detailed absorption mechanisms using complex perfusion media, which increase the biorelevance of the model.
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| 32. |
- Roos, Carl, et al.
(författare)
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Mechanistic modelling of intestinal drug absorption : the in vivo effects of nanoparticles, hydrodynamics, and colloidal structures
- 2018
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 133, s. 70-76
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Tidskriftsartikel (refereegranskat)abstract
- Particle size reduction is a traditional approach to increase the intestinal absorption of active pharmaceutical ingredients with poor intestinal solubility, by increasing the particle dissolution rate. However, an increase in the dissolution rate cannot always fully explain the effects of nanoformulations, and a method of assessing the potential benefits of a nanoformulation in vivo would hence be of great value in drug development. A novel mathematical model of a nanoformulation, including interlinked descriptions of the hydrodynamics, particle dissolution and diffusion of particles and colloidal structures (CS), was developed to predict the combined in vivo effects of these mechanisms on drug absorption. The model successfully described previously reported in vivo observations of nanoformulated aprepitant in rats, at various drug concentrations and in the presence or absence of CS. The increase in absorption rate was explained as a direct consequence of the increased drug concentration at the membrane, caused by the contributing effects of the diffusion of both nanoparticles and CS into which the drug had partitioned. Further simulations supported the conclusion that the model can be applied during drug development to provide a priori assessments of the potential benefits of nanoformulations.
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| 33. |
- Roos, Carl, et al.
(författare)
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Regional Intestinal Permeability in Rats : A Comparison of Methods
- 2017
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 14:12, s. 4252-4261
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Tidskriftsartikel (refereegranskat)abstract
- Currently, the screening of new drug candidates for intestinal permeation is typically based on in vitro models which give no information regarding regional differences along the gut. When evaluation of intestinal permeability by region is undertaken, two preclinical rat models are commonly used, the Ussing chamber method and single-pass intestinal perfusion (SPIP). To investigate the robustness of in vivo predictions of human intestinal permeability, a set of four model compounds was systematically investigated in both these models, using tissue specimens and segments from the jejunum, ileum, and colon of rats from the same genetic strain. The influence of luminal pH was also determined at two pH levels. Ketoprofen had high and enalaprilat had low effective (P-eff) and apparent (P-app) permeability in all three regions and at both pH levels. Metoprolol had high P-eff in all regions and at both pHs and high P-app at both pHs and in all regions except the jejunum, where P-app was low. Atenolol had low P-eff in all regions and at both pHs, but had high P-app at pH 6.5 and low P-app at pH 7.4. There were good correlations between these rat in situ P-eff (SPIP) and human in vivo P-eff determined previously for the same compounds by both intestinal perfusion of the jejunum and regional intestinal dosing. The results of this study indicate that both investigated models are suitable for determining the regional permeability of the intestine; however, the SPIP model seems to be the more robust and accurate regional permeability model.
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| 34. |
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| 35. |
- Sidrén, Jonas, 1723-1799
(författare)
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Dissertatio medica, de lumbagine, quam, venia experient. facult. medicæ, in regia academia Upsaliensi, præside, D. Doct. Jona Sidrén, ... Johannes Carolus Roos, Stockholmiensis. In auditorio Carolino majori, die IX. Decembris a. MDCCLXXV.
- 1775
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
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| 36. |
- Sjögren, Erik, et al.
(författare)
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Human in Vivo Regional Intestinal Permeability : Quantitation Using Site-Specific Drug Absorption Data
- 2015
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 12:6, s. 2026-2039
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Tidskriftsartikel (refereegranskat)abstract
- Application of information on regional intestinal permeability has been identified as a key aspect of successful pharmaceutical product development. This study presents the results and evaluation of an approach for the indirect estimation of site-specific in vivo intestinal effective permeability (P-eff) in humans. Plasma concentrationtime profiles from 15 clinical studies that administered drug solutions to specific intestinal regions were collected and analyzed. The intestinal absorption rate for each drug was acquired by deconvolution, using historical intravenous data as reference, and used with the intestinal surface area and the dose remaining in the lumen to estimate the Peff. Forty-three new Peff values were estimated (15 from the proximal small intestine, 11 from the distal small intestine, and 17 from the large intestine) for 14 active pharmaceutical ingredients representing a wide range of biopharmaceutical properties. A good correlation (r(2) = 0.96, slope = 1.24, intercept = 0.030) was established between these indirect jejunal P-eff estimates and jejunal P-eff measurements determined directly using the single-pass perfusion double balloon technique. On average, P-eff estimates from the distal small intestine and large intestine were 90% and 40%, respectively, of those from the proximal small intestine. These results support the use of the evaluated deconvolution method for indirectly estimating regional intestinal P-eff in humans. This study presents the first comprehensive data set of estimated human regional intestinal permeability values for a range of drugs. These biopharmaceutical data can be used to improve the accuracy of gastrointestinal absorption predictions used in drug development decision-making.
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| 37. |
- Stavenow, Jasmine, et al.
(författare)
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Sowerby’s Beaked Whales (Mesoplodon bidens) in the Skagerrak and Adjacent Waters: Historical Records and Recent Post-Mortem Findings
- 2022
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Ingår i: Oceans. - : MDPI AG. - 2673-1924. ; 3:3, s. 250-267
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Tidskriftsartikel (refereegranskat)abstract
- In contrast to sparse historical observational records, five Sowerby’s beaked whales (SBW) stranded and died in Swedish waters between 2015 and 2020. Here we summarize historical records of SBWs in the Skagerrak basin and adjacent waters. The three recent stranding events from Sweden are described, and the post-mortem findings, including diet analysis, from the five SBWs are presented. Of 30 historical records of SBWs observations since 1869, 13 (43%) were documented between 2010 and 2021, and records between July and November were the most frequent. The recent stranding events occurred in October 2015 (n = 1), August 2019 (n = 3) and July 2020 (n = 1). Four of the SBWs were examined through necropsy, and one was sampled in the field. They were all sub-adults and included a single female and four males. The causes of death were emaciation, euthanasia due to traumatic injury, and live stranding of undetermined cause. Two SBWs each had a focal bone lesion consistent with osteomyelitis. Other findings included pox-like dermatitis, trauma, focal granulomas in a lymph node and intestine, and ulceration of the stomach. CT scans were performed on the heads of two animals, with inconclusive results. Three SBWs had hard parts in the gastrointestinal tract that mainly consisted of otoliths from several fish species. An eDNA-analysis confirmed and supplemented the diet analysis, revealing 17 fish species in total, including species not previously described as prey for SBW, such as Pleuronectidae spp. The apparent increase in observational records since 2010 may indicate a shift in SBW distribution or changing threats to these animals. Our results support and expand theories on SBW movements and provide data on the biology and health of this poorly known species, which are valuable for conservation and legislation efforts.
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| 38. |
- Sörelius, Karl, et al.
(författare)
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Endovascular treatment of mycotic aortic aneurysms: a European multicenter study.
- 2014
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 1524-4539 .- 0009-7322. ; 130:24, s. 2136-42
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Tidskriftsartikel (refereegranskat)abstract
- Mycotic aortic aneurysm (MAA) is a rare and life-threatening disease. The aim of this European multicenter collaboration was to study the durability of endovascular aortic repair (EVAR) of MAA, by assessing late infection-related complications and long-term survival.
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| 39. |
- Sörelius, Karl, 1981-, et al.
(författare)
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Nationwide Study on Treatment of Mycotic Thoracic Aortic Aneurysms
- 2019
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Saunders Elsevier. - 1078-5884 .- 1532-2165. ; 57:2, s. 239-246
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Mycotic aortic aneurysms are rare, life threatening, and complex. This nationwide study aimed to assess outcome after repair of mycotic thoracic aortic aneurysms (MTAAs). Methods: Patients treated in Sweden for MTAAs between 2000 and 2016 were identified in the Swedish vascular registry (2010-16) and local patient registries (2000-09). Primary outcome was survival, and secondary outcomes included surgical strategy, rate of infection related complications (IRC), and re-operations. Results: Fifty-two patients (median age 71 +/- 8.1 years; 28 [54%] men, 13 [25%] ruptured) were identified (3.6% of all thoracic aortic aneurysm repairs in Sweden). Aneurysm location was aortic arch (n = 6; 11%), descending aorta (n = 42; 81%), and multiple locations (n = 4; 8%). Twenty-nine (56%) patients had positive cultures; the most prevalent agent was Staphylococcus aureus (n = 16; 31%). Operative techniques included thoracic endovascular aortic repair (TEVAR; n = 35 [67%]), fenestrated/branched TEVAR (n = 8; 15%), hybrid repair (n = 7; 14%), and open patch repair (n = 2; 4%). Survival was 92% (95% confidence interval [CI] 88-96) at 30 days, 88% (95% CI 84-93) at three months, 78% (73-84) at one year, and 71% (64-77) at five years. The mean follow up among survivors (> 90 days) was 45 months (range 4-216 months). Antibiotics were administered for a median of 15 weeks (range 0-220 weeks). IRCs occurred in nine patients (17%): sepsis (n = 3), graft infection (n = 3), recurrent mycotic aneurysm (n = 1), aorto-oesophageal/bronchial fistula (n = 2). Six (67%) IRCs were fatal; 80% occurred within the first year. Re-operations were performed in nine patients (17%). Conclusions: TEVAR was often used as treatment for MTAAs, with acceptable short- and long-term survival when compared with open cohorts in the literature. IRCs are of concern and warrant follow up and long-term antibiotic treatment.
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