| 1. |
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| 2. |
- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 3. |
- Pekkinen, M., et al.
(författare)
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Osteoporosis and skeletal dysplasia caused by pathogenic variants in SGMS2
- 2019
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Ingår i: Jci Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 4:7
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Tidskriftsartikel (refereegranskat)abstract
- Mechanisms leading to osteoporosis are incompletely understood. Genetic disorders with skeletal fragility provide insight into metabolic pathways contributing to bone strength. We evaluated 6 families with rare skeletal phenotypes and osteoporosis by next-generation sequencing. In all the families, we identified a heterozygous variant in SGMS2, a gene prominently expressed in cortical bone and encoding the plasma membrane-resident sphingomyelin synthase SMS2. Four unrelated families shared the same nonsense variant, c.148C>T (p.Arg50*), whereas the other families had a missense variant, c.185T>G (p.IIe62Ser) or c.191T>G (p.Met64Arg). Subjects with p.Arg50* presented with childhood-onset osteoporosis with or without cranial sclerosis. Patients with p.IIe62Ser or p.Met64Arg had a more severe presentation, with neonatal fractures, severe short stature, and spondylometaphyseal dysplasial Several subjects had experienced peripheral facial nerve palsy or other neurological manifestations. Bone biopsies showed markedly altered bone material characteristics, including defective bone mineralization. Osteoclast formation and function in vitro was normal. While the p.Arg50* mutation yielded a catalytically inactive enzyme, p.IIe62Ser and p.Met64Arg each enhanced the rate of de novo sphingomyelin production by blocking export of a functional enzyme from the endoplasmic reticulum. SGMS2 pathogenic variants underlie a spectrum of skeletal conditions, ranging from isolated osteoporosis to complex skeletal dysplasia, suggesting a critical role for plasma membrane-bound sphingomyelin metabolism in skeletal homeostasis.
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| 4. |
- Charalampous, P., et al.
(författare)
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Methodological considerations in injury burden of disease studies across Europe: a systematic literature review
- 2022
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Ingår i: Bmc Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 22:1
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Forskningsöversikt (refereegranskat)abstract
- Background Calculating the disease burden due to injury is complex, as it requires many methodological choices. Until now, an overview of the methodological design choices that have been made in burden of disease (BoD) studies in injury populations is not available. The aim of this systematic literature review was to identify existing injury BoD studies undertaken across Europe and to comprehensively review the methodological design choices and assumption parameters that have been made to calculate years of life lost (YLL) and years lived with disability (YLD) in these studies. Methods We searched EMBASE, MEDLINE, Cochrane Central, Google Scholar, and Web of Science, and the grey literature supplemented by handsearching, for BoD studies. We included injury BoD studies that quantified the BoD expressed in YLL, YLD, and disability-adjusted life years (DALY) in countries within the European Region between early-1990 and mid-2021. Results We retrieved 2,914 results of which 48 performed an injury-specific BoD assessment. Single-country independent and Global Burden of Disease (GBD)-linked injury BoD studies were performed in 11 European countries. Approximately 79% of injury BoD studies reported the BoD by external cause-of-injury. Most independent studies used the incidence-based approach to calculate YLDs. About half of the injury disease burden studies applied disability weights (DWs) developed by the GBD study. Almost all independent injury studies have determined YLL using national life tables. Conclusions Considerable methodological variation across independent injury BoD assessments was observed; differences were mainly apparent in the design choices and assumption parameters towards injury YLD calculations, implementation of DWs, and the choice of life table for YLL calculations. Development and use of guidelines for performing and reporting of injury BoD studies is crucial to enhance transparency and comparability of injury BoD estimates across Europe and beyond.
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| 5. |
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| 6. |
- Govaere, O., et al.
(författare)
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Macrophage scavenger receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease
- 2022
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Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 76:5, s. 1001-1012
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Obesity-associated inflammation is a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the role of macrophage scavenger receptor 1 (MSR1, CD204) remains incompletely understood. Methods: A total of 170 NAFLD liver biopsies were processed for transcriptomic analysis and correlated with clinicopathological features. Msr1-/- and wild-type mice were subjected to a 16-week high-fat and high-cholesterol diet. Mice and ex vivo human liver slices were treated with a monoclonal antibody against MSR1. Genetic susceptibility was assessed using genome-wide association study data from 1,483 patients with NAFLD and 430,101 participants of the UK Biobank. Results: MSR1 expression was associated with the occurrence of hepatic lipid-laden foamy macrophages and correlated with the degree of steatosis and steatohepatitis in patients with NAFLD. Mice lacking Msr1 were protected against diet-induced metabolic disorder, showing fewer hepatic foamy macrophages, less hepatic inflammation, improved dyslipidaemia and glucose tolerance, and altered hepatic lipid metabolism. Upon induction by saturated fatty acids, MSR1 induced a pro-inflammatory response via the JNK signalling pathway. In vitro blockade of the receptor prevented the accumulation of lipids in primary macrophages which inhibited the switch towards a pro-inflammatory phenotype and the release of cytokines such as TNF-ɑ. Targeting MSR1 using monoclonal antibody therapy in an obesity-associated NAFLD mouse model and human liver slices resulted in the prevention of foamy macrophage formation and inflammation. Moreover, we identified that rs41505344, a polymorphism in the upstream transcriptional region of MSR1, was associated with altered serum triglycerides and aspartate aminotransferase levels in a cohort of over 400,000 patients. Conclusions: Taken together, our data suggest that MSR1 plays a critical role in lipid-induced inflammation and could thus be a potential therapeutic target for the treatment of NAFLD. Lay summary: Non-alcoholic fatty liver disease (NAFLD) is a chronic disease primarily caused by excessive consumption of fat and sugar combined with a lack of exercise or a sedentary lifestyle. Herein, we show that the macrophage scavenger receptor MSR1, an innate immune receptor, mediates lipid uptake and accumulation in Kupffer cells, resulting in liver inflammation and thereby promoting the progression of NAFLD in humans and mice. © 2021 The Authors
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| 7. |
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| 8. |
- Molinaro, Antonio, et al.
(författare)
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Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism.
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| 9. |
- Orce, J. N., et al.
(författare)
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Reorientation-effect measurement of the (2+ 1 Eˆ22+ 1) matrix element in 10Be
- 2012
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Ingår i: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 86:4
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Tidskriftsartikel (refereegranskat)abstract
- The highly-efficient and segmented TIGRESS gamma-ray spectrometer at TRIUMF has been used to perform a reorientation-effect Coulomb-excitation study of the 2(1)(+) state at 3.368 MeV in Be-10. This is the first Coulomb-excitation measurement that enables one to obtain information on diagonal matrix elements for such a high-lying first excited state from gamma-ray data. With the availability of accurate lifetime data, a value of -0.110 +/- 0.087 eb is determined for the diagonal matrix element, which assuming the rotor model, leads to a negative spectroscopic quadrupole moment of Q(S)(2(1)(+)) = -0.083 +/- 0.066 eb. This result is in agreement with both no-core shell-model calculations performed in this work with the CD-Bonn 2000 two-nucleon potential and large shell-model spaces, and Green's function Monte Carlo predictions with two-plus three-nucleon potentials.
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| 10. |
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| 11. |
- Andrikopoulos, Petros, et al.
(författare)
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Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide
- 2023
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.
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| 12. |
- Bel Lassen, P., et al.
(författare)
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Protein intake, metabolic status and the gut microbiota in different ethnicities: Results from two independent cohorts
- 2021
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 13:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Protein intake has been associated with the development of pre-diabetes (pre-T2D) and type 2 diabetes (T2D). The gut microbiota has the capacity to produce harmful metabolites derived from dietary protein. Furthermore, both the gut microbiota composition and metabolic status (e.g., insulin resistance) can be modulated by diet and ethnicity. However, to date most studies have predominantly focused on carbohydrate and fiber intake with regards to metabolic status and gut microbiota composition. Objectives: To determine the associations between dietary protein intake, gut microbiota composition, and metabolic status in different ethnicities. Methods: Separate cross-sectional analysis of two European cohorts (MetaCardis, n = 1759; HELIUS, n = 1528) including controls, patients with pre-T2D, and patients with T2D of Caucasian/non-Caucasian origin with nutritional data obtained from Food Frequency Questionnaires and gut microbiota composition. Results: In both cohorts, animal (but not plant) protein intake was associated with pre-T2D status and T2D status after adjustment for confounders. There was no significant association between protein intake (total, animal, or plant) with either gut microbiota alpha diversity or beta diversity, regardless of ethnicity. At the species level, we identified taxonomical signatures associated with animal protein intake that overlapped in both cohorts with different abundances according to metabolic status and ethnicity. Conclusions: Animal protein intake is associated with pre-T2D and T2D status but not with gut microbiota beta or alpha diversity, regardless of ethnicity. Gut microbial taxonomical signatures were identified, which could function as potential modulators in the association between dietary protein intake and metabolic status. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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| 13. |
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| 14. |
- Long, M., et al.
(författare)
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Endocrine-Disrupting Effects of Compounds in Danish Streams
- 2014
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Ingår i: Archives of Environmental Contamination and Toxicology. - : Springer Science and Business Media LLC. - 0090-4341 .- 1432-0703. ; 66:1, s. 1-18
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Tidskriftsartikel (refereegranskat)abstract
- Effluents from municipal wastewater-treatment plants and scattered dwellings, as well as runoff from agricultural fields, are sources of endocrine-disrupting compounds (EDCs) in the aquatic environment. The present study investigated the correlation between the occurrence of EDCs in nine Danish streams using passive samplers (polar organic integrative samplers and silicone membranes) and determined their possible biological effects as assessed by mammal cell cultures and the mussel (Unio tumidus). The passive samplers and mussels were exposed simultaneously at the study sites. The extracts from the passive samplers were used to measure the concentrations of EDCs and the biological effects on the estrogen (ER), androgen (AR), and aryl hydrocarbon (AhR)-receptor transactivation. Male mussels were investigated for biomarkers of endocrine effects, such as the levels of vitellogenin-like proteins measured as alkali-labile phosphate (ALP). EDC concentrations, hormone-receptor transactivation (ER, AR, AhR), and level of ALP were greater downstream of wastewater-treatment plants compared with upstream sites and sites supposed to be relatively nonimpacted by wastewater. Furthermore, there was a significant positive correlation between in vitro AhR transactivation and frequency of ALP of male mussels. We conclude that wastewater effluent is an important source of endocrine-disrupting effects in the aquatic environment and that the combination of biological effect measurements and chemical analyses based on passive sampling is useful in the assessment of the ecological state of the aquatic environment.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Takala, S., et al.
(författare)
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Practice patterns in diagnostics, staging, and management strategies of gallbladder cancer among Nordic tertiary centers
- 2023
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Ingår i: Scandinavian Journal of Surgery. - : Sage Publications. - 1457-4969 .- 1799-7267. ; 112:3
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: Gallbladder cancer (GBC) is a rare malignancy in the Nordic countries and no common Nordic treatment guidelines exist. This study aimed to characterize the current diagnostic and treatment strategies in the Nordic countries and disclose differences in these strategies. Methods: This was a survey study with a cross-sectional questionnaire of all 19 university hospitals providing curative-intent surgery for GBC in Sweden, Norway, Denmark, and Finland. Results: In all Nordic countries except Sweden, neoadjuvant/downstaging chemotherapy was used in GBC patients. In T1b and T2, majority of the centers (15-18/19) performed extended cholecystectomy. In T3, majority of the centers (13/19) performed cholecystectomy with resection of segments 4b and 5. In T4, majority of the centers (12-14/19) chose palliative/oncological care. The centers in Sweden extended lymphadenectomy beyond the hepatoduodenal ligament, whereas all other Nordic centers usually limited lymphadenectomy to the hepatoduodenal ligament. All Nordic centers except those in Norway used adjuvant chemotherapy routinely for GBC. There were no major differences between the Nordic centers in diagnostics and follow-up. Conclusions: The surgical and oncological treatment strategies of GBC vary considerably between the Nordic centers and countries.
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| 19. |
- Agnelli, G, et al.
(författare)
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Safety assessment of new antithrombotic agents : Lessons from the EXTEND study on ximelagatran.
- 2009
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 123:3, s. 488-497
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Ximelagatran, the first oral direct thrombin inhibitor, was shown to be an effective antithrombotic agent but was associated with potential liver toxicity after prolonged administration. OBJECTIVES AND METHODS: The aim of the EXTEND study was to assess safety and efficacy of extended administration (35 days) of ximelagatran or enoxaparin for the prevention of venous thromboembolism after elective hip replacement and hip fracture surgery. A follow-up period, including assessment of liver enzymes (in particular alanine aminotransferase; ALAT), until post-operative day 180 was planned, with visits at days 56 and 180. RESULTS: Randomization and administration of study drugs were stopped following a report of serious liver injury occurring 3 weeks after completion of ximelagatran treatment. At the time of study termination, 1158 patients had been randomized and 641 had completed the 35-day treatment; with 303 ximelagatran and 265 enoxaparin patients remaining in the study through to the day 56 follow-up visit. Overall, 58 patients showed an ALAT increase to >2x upper limit of normal: 31 treated with enoxaparin, 27 with ximelagatran. Three ximelagatran patients also showed symptoms potentially related to liver toxicity. Eleven ximelagatran patients showed an ALAT increase after study treatment ended. The clinical development of ximelagatran was terminated and the drug withdrawn from the market. Evaluation of the relative efficacy of the two treatments as specified in the protocol was impossible due to the premature termination of the study. CONCLUSIONS: Prolonged administration of ximelagatran was associated with an increased risk of liver toxicity. In a substantial proportion of patients, ALAT increase occurred after treatment withdrawal. The findings seen with ximelagatran should be considered when designing studies with new antithrombotic agents.
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| 20. |
- Andersson, Anna, et al.
(författare)
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Paired multiplex reverse-transcriptase polymerase chain reaction (PMRT-PCR) analysis as a rapid and accurate diagnostic tool for the detection of MLL fusion genes in hematologic malignancies
- 2001
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Ingår i: Leukemia. - 1476-5551. ; 15:8, s. 1293-1293
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Tidskriftsartikel (refereegranskat)abstract
- The MLL gene in chromosome band 11q23 is frequently rearranged in acute lymphoblastic and acute myeloid leukemias. To date, more than 50 different chromosomal regions are known to participate in translocations involving 11q23, many of which affect MLL. The pathogenetically important outcome of these rearrangements is most likely the creation of a fusion gene consisting of the 5' part of the MLL gene and the 3' end of the partner gene. Although abnormalities of the MLL gene as such are generally associated with poor survival, recent data suggest that the prognostic impact varies among the different fusion genes generated. Hence, detection of the specific chimeric gene produced is important for proper prognostication and clinical decision making. We have developed a paired multiplex reverse-transcriptase polymerase chain reaction analysis to facilitate a rapid and accurate detection of the most frequent MLL fusion genes in adult and childhood acute leukemias. To increase the specificity, two sets of primers were designed for each fusion gene, and these paired primer sets were run in parallel in two separate multiplex one-step PCR reactions. Using the described protocol, we were able to amplify successfully, in one single assay, the six clinically relevant fusion genes generated by the t(4;11)(q21;q23) [MLL/AF4], t(6;11)(q27;q23) [MLL/AF6], t(9;11)(p21-22;q23) [MLL/AF9], t(10;11)(p11-13;q23) [MLL/AF10], t(11;19)(q23;p13.1) [MLL/ELL], and t(11;19)(q23; p13.3) [MLL/ENL] in cell lines, as well as in patient material.
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| 21. |
- Attaye, Ilias, et al.
(författare)
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Protein supplementation changes gut microbial diversity and derived metabolites in subjects with type 2 diabetes
- 2023
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Ingår i: ISCIENCE. - 2589-0042. ; 26:8
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Tidskriftsartikel (refereegranskat)abstract
- High-protein diets are promoted for individuals with type 2 diabetes (T2D). How-ever, effects of dietary protein interventions on (gut-derived) metabolites in T2D remains understudied. We therefore performed a multi-center, randomized -controlled, isocaloric protein intervention with 151 participants following either 12-week high-protein (HP; 30Energy %, N = 78) vs. low-protein (LP; 10 Energy%, N = 73) diet. Primary objectives were dietary effects on glycemic control which were determined via glycemic excursions, continuous glucose monitors and HbA1c. Secondary objectives were impact of diet on gut microbiota composition and-derived metabolites which were determined by shotgun-metagenomics and mass spectrometry. Analyses were performed using delta changes adjusting for center, baseline, and kidney function when appropriate. This study found that a short-term 12-week isocaloric protein modulation does not affect glycemic parameters or weight in metformin-treated T2D. However, the HP diet slightly worsened kidney function, increased alpha-diversity, and production of potentially harmful microbiota-dependent metabolites, which may affect host metabolism upon prolonged exposure.
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| 22. |
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| 23. |
- Dahl, O. E., et al.
(författare)
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Major joint replacement. A model for antithrombotic drug development: from proof-of-concept to clinical use
- 2008
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Ingår i: International angiology. - 0392-9590. ; 27:1, s. 60-7
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Development of antithrombotic compounds has traditionally been performed in patients undergoing total hip and knee replacement surgery. A high number of asymptomatic deep-vein thromboses are radiologically detectable, and bleeding and other adverse events (AE) are easy to observe. However, standardization of study procedures and endpoints in early proof-of-concept studies and late pure clinical endpoint studies has been lacking. This has made comparison between studies difficult, economic analyses speculative and potential benefits of applying the drug regimen in non-selected patients uncertain. In this paper, the International Surgical Thrombosis Forum proposes a strategy for the clinical investigation of new pharmacological agents for the prophylaxis of postoperative thrombotic events. METHODS: First, dose titration safety studies of short duration, in highly selected patients using objective venographic endpoints are recommended. Bleeding should be divided into the quantified volume of surgical bleeding and other adjudicated clinical bleeding events. The number of AE should be described for each dose step and classified according to International Coding of Diagnoses (ICD). Second, a dose confirmatory study of moderate exposure period and sufficient follow-up time is recommended. The exclusion criteria should be restricted to contraindications of the compared drugs and technical procedure. RESULTS: The efficacy, bleeding and AE should be similar to those used in dose-titration studies. In addition, the failure rate of the drug to exert its effect and the net clinical benefit should be calculated. CONCLUSION: Finally, trials with simple clinical endpoints and long follow-up should be conducted to evaluate the potential benefits of the drug-regimen in non-selected populations.
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| 24. |
- Egardt, Jenny, 1981, et al.
(författare)
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Release of PAHs and heavy metals in coastal environments linked to leisure boats
- 2018
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Ingår i: Marine Pollution Bulletin. - : Elsevier BV. - 0025-326X. ; 127, s. 664-671
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Tidskriftsartikel (refereegranskat)abstract
- Leisure boats are responsible for elevated levels of heavy metals and PAHs in sediments in- and near marinas and natural harbours. As these compounds are released directly into the water column they also pose a threat to organisms in the pelagic environment. Passive samplers were deployed during peak and post tourist season in the water column of natural harbours, leisure boat waterways and small marinas to measure the dissolved fraction of PAHs and metal ions. Differences between seasons indicative of leisure boat activities were found as PAH composition differed between peak and post season for natural harbours and waterways, where heavier PAHs increased during peak season. During peak season, metal samplers were covered by biofouling, which likely affected the uptake. Post season metal concentrations differ between locations, with concentrations exceeding quality standards at near mainland locations where boats are maintained, compared to the sites in the archipelago. © 2017 Elsevier Ltd
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| 25. |
- Eriksson, Bengt I., 1946, et al.
(författare)
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Partial factor IXa inhibition with TTP889 for prevention of venous thromboembolism: an exploratory study
- 2008
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7836. ; 6:3, s. 457-63
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Inhibitors of factor (F) IXa show potent antithrombotic activity with a low risk of bleeding in preclinical models. We investigated the anticoagulant potential of oral TTP889, a small molecule that inhibits up to 90% of FIXa activity at therapeutic doses, using a clinical model of extended prophylaxis in hip fracture surgery (HFS). METHODS: In this multicenter, randomized, double-blind study, 261 patients received oral TTP889 (300 mg once daily) or placebo starting 6-10 days after HFS, and standard thromboprophylaxis for 5-9 days. Treatment was continued for 3 weeks and all patients then underwent mandatory bilateral venography. The primary efficacy outcome was venous thromboembolism (VTE; venographic or symptomatic deep vein thrombosis or pulmonary embolism) during treatment, and it was evaluated centrally by an independent adjudication panel. The main safety outcome was bleeding (major, clinically relevant non-major, and minor events). RESULTS: Two hundred and twelve patients with an evaluable venogram were included in the efficacy analysis. The primary efficacy outcome occurred in 32.1% (35/109) of patients who had been allocated TTP889, and 28.2% (29/103) of patients on placebo (P = 0.58). There were no major bleeding events, and only two clinically relevant non-major bleeding events with TTP889. CONCLUSION: Partial FIXa inhibition with TTP889 300 mg daily was not effective for extended prevention of VTE after standard prophylaxis for up to 9 days. Coupled with the low incidence of bleeding episodes, this suggests a lack of antithrombotic potential. Further investigation of TTP889 in different clinical settings is needed. (Clinical trial registration information URL: http://www.clinicaltrials.gov. Unique identifier: NCT00119457).
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| 26. |
- Hakansson, P., et al.
(författare)
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Establishment and phenotypic characterization of human U937 cells with inducible P210 BCR/ABL expression reveals upregulation of CEACAM1 (CD66a)
- 2004
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 18:3, s. 538-47
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Tidskriftsartikel (refereegranskat)abstract
- Chronic myeloid leukemia (CML) is characterized by the expression of the P210 BCR/ABL fusion protein. The molecular mechanisms behind this oncogene-mediated hematological disease are, however, not fully understood. Here, we describe the establishment and phenotypic characterization of U937 cells in which P210 BCR/ABL can be conditionally expressed using tetracycline. The induction of BCR/ABL in the obtained clones resulted in a rapid phosphorylation of the STAT1, STAT3 and STAT5 molecules, consistent with the findings in other model systems. Phenotypic characterization of the clones revealed that BCR/ABL induces a slight decrease in the proliferation and viability, without a marked effect on cell cycle distribution, the rate of apoptosis or on cellular differentiation, as judged by several cell surface markers and capacity to reduce nitro blue tetrazolium. Interestingly, BCR/ABL was found to upregulate the expression of carcinoembryonic-related antigen (CEA)CAM1 (CD66a), which is a plasma membrane-linked glycoprotein belonging to the CEAs and involved in signal transduction and cellular adhesion. The expression of CEACAM1 was reversible upon imatinib treatment in BCR/ABL-expressing U937 cells as well as in BCR/ABL-positive K562 cells. The established cell lines may prove useful in further modeling and dissection of BCR/ABL-induced leukemogenesis.
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| 27. |
- Hannemann, P, et al.
(författare)
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Patterns in current anaesthesiological peri-operative practice for colonic resections : a survey in five northern-European countries
- 2006
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Ingår i: Acta Anaesthesiologica Scandinavica. - Oxon, United Kingdom : Blackwell Publishing. - 0001-5172 .- 1399-6576. ; 50:9, s. 1152-60
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Tidskriftsartikel (refereegranskat)abstract
- Background: For colorectal surgery, evidence suggests that optimal management includes: no pre-operative fasting, a thoracic epidural analgesia continued for 2 days post-operatively, and avoidance of fluid overload. In addition, no long-acting benzodiazepines on the day of surgery and use of short-acting anaesthetic medication may be beneficial. We examined whether these strategies have been adopted in five northern-European countries.Methods: In 2003, a questionnaire concerning peri-operative anaesthetic routines in elective, open colonic cancer resection was sent to the chief anaesthesiologist in 258 digestive surgical centres in Scotland, the Netherlands, Denmark, Sweden and Norway.Results: The response rate was 74% (n = 191). Although periods of pre-operative fasting up to 48 h were reported, most (> 85%) responders in all countries declared to adhere to guidelines for pre-operative fasting and oral clear liquids were permitted until 2-3 h before anaesthesia. Solid food was permitted up to 6-8 h prior to anaesthesia. In all countries more than 85% of the responders indicated that epidural anaesthesia was routinely used. Except for Denmark, long-acting benzodiazepines were still widely used. Short-acting anaesthetics were used in all countries except Scotland where isoflurane is the anaesthetic of choice. With the exception of Denmark, intravenous fluids were used unrestrictedly.Conclusion: In northern Europe, most anaesthesiologists adhere to evidence-based optimal management strategies on pre-operative fasting, thoracic epidurals and short-acting anaesthetics. However, premedication with longer-acting agents is still common. Avoidance of fluid overload has not yet found its way into daily practice. This may leave patients undergoing elective colonic surgery at risk of oversedation and excessive fluid administration with potential adverse effects on surgical outcome.
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| 28. |
- Henderson, J., et al.
(författare)
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Coulomb excitation of the vertical bar T-z vertical bar=1/2, A=23 mirror pair
- 2022
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Ingår i: PHYSICAL REVIEW C. - 2469-9985 .- 2469-9993. ; 105:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Electric-quadrupole (E2) strengths relate to the underlying quadrupole deformation of a nucleus and present a challenge for many nuclear theories. Mirror nuclei in the vicinity of the line of N = Z represent a convenient laboratory for testing deficiencies in such models, making use of the isospin symmetry of the systems. Purpose: Uncertainties associated with literature E2 strengths in Mg-23 are some of the largest in T-z = vertical bar 1/2 vertical bar nuclei in the sd shell. The purpose of the present paper is to improve the precision with which these values are known, to enable better comparison with theoretical models. Methods: Coulomb-excitation measurements of Mg-23 and Na-23 were performed at the TRIUMF-ISAC facility using the TIGRESS spectrometer. They were used to determine the E2 matrix elements of mixed E2/M1 transitions. Results: Reduced E2 transition strengths, B(E2), were extracted for Mg-23 and Na-23. Their precision was improved by factors of approximately 6 for both isotopes, while agreeing within uncertainties with previous measurements. Conclusions: A comparison was made with both shell-model and ab initio valence-space in-medium similarity renormalization group calculations. Valence-space in-medium similarity renormalization group calculations were found to underpredict the absolute E2 strength, in agreement with previous studies.
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| 29. |
- Hendry, P. O., et al.
(författare)
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Determinants of outcome after colorectal resection within an enhanced recovery programme
- 2009
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Ingår i: British Journal of Surgery. - Oxford : Blackwell. - 0007-1323 .- 1365-2168. ; 96:2, s. 197-205
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Postoperative outcomes were studied in relation to adverse nutritional risk (body mass index (BMI) below 20 kg/m(2)), advanced age (80 years or more) and co-morbidity (American Society of Anesthesiologists (ASA) grade III-IV) in patients undergoing colorectal resection within an enhanced recovery after surgery programme. METHODS: Outcomes were audited prospectively in 1035 patients. Morbidity and mortality were compared with those predicted using the Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity, and a multivariable model was used to determine independent predictors of outcome. RESULTS: Postoperative morbidity was lower than predicted (observed to expected 0.68; P < 0.001). Independent predictors of delayed mobilization were ASA III-IV (P < 0.001) and advanced age (P = 0.025). Prolonged hospital stay was related to advanced age (P = 0.002), ASA III-IV (P < 0.001), male sex (P = 0.037) and rectal surgery (P < 0.001). Morbidity was related to ASA III-IV (P = 0.004), male sex (P = 0.023) and rectal surgery (P = 0.002). None of the factors predicted 30-day mortality. CONCLUSION: Age and nutritional status were not independent determinants of morbidity or mortality. Pre-existing co-morbidity was an independent predictor of several outcomes.
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| 30. |
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| 31. |
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| 32. |
- Hruska, Katrin, et al.
(författare)
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Template for uniform reporting of emergency department measures, consensus according to the Utstein method
- 2019
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Ingår i: European journal of emergency medicine. - : Lippincott Williams & Wilkins. - 0969-9546 .- 1473-5695. ; 26:6, s. 417-422
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To develop a template for uniform reporting of standardized measuring and describing of care provided in the emergency department (ED).Methods: An international group of experts in emergency medicine, with broad experience from different clinical settings, met in Utstein, Norway. Through a consensus process, a limited number of measures that would accurately describe an ED were chosen and a template was developed.Results: The final measures to be reported and their definitions were grouped into six categories: Structure, Staffing and governance, Population, Process times, Hospital and healthcare system and Outcomes. The template for Utstein-style uniform reporting is presented.Conclusion: The suggested template is intended for use in studies carried out in EDs to improve comparability and knowledge translation.
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| 33. |
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| 34. |
- Lassen, Kristoffer, et al.
(författare)
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Consensus review of optimal perioperative care in colorectal surgery : Enhanced Recovery After Surgery (ERAS) Group recommendations
- 2009
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Ingår i: Archives of surgery (Chicago. 1960). - : American Medical Association (AMA). - 0004-0010 .- 1538-3644. ; 144:10, s. 961-969
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVES: To describe a consensus review of optimal perioperative care in colorectal surgery and to provide consensus recommendations for each item of an evidence-based protocol for optimal perioperative care. DATA SOURCES: For every item of the perioperative treatment pathway, available English-language literature has been examined. STUDY SELECTION: Particular attention was paid to meta-analyses, randomized controlled trials, and systematic reviews. DATA EXTRACTION: A consensus recommendation for each protocol item was reached after critical appraisal of the literature by the group. DATA SYNTHESIS: For most protocol items, recommendations are based on good-quality trials or meta-analyses of such trials. CONCLUSIONS: The Enhanced Recovery After Surgery (ERAS) Group presents a comprehensive evidence-based consensus review of perioperative care for colorectal surgery. It is based on the evidence available for each element of the multimodal perioperative care pathway.
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| 35. |
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| 36. |
- Lill, Christina M., et al.
(författare)
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The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:12, s. 1407-1416
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Tidskriftsartikel (refereegranskat)abstract
- A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Ab42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 x 10(-25)). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR 5 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR 5 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Ab42 suggesting that TREM2's role in AD may involve tau dysfunction. (C) 2015 The Alzheimer's Association.
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| 37. |
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| 38. |
- Lokhorst, Henk M, et al.
(författare)
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Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma.
- 2015
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 373:13, s. 1207-1219
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Tidskriftsartikel (refereegranskat)abstract
- Background Multiple myeloma cells uniformly overexpress CD38. We studied daratumumab, a CD38-targeting, human IgG1κ monoclonal antibody, in a phase 1-2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy. Methods In part 1, the dose-escalation phase, we administered daratumumab at doses of 0.005 to 24 mg per kilogram of body weight. In part 2, the dose-expansion phase, 30 patients received 8 mg per kilogram of daratumumab and 42 received 16 mg per kilogram, administered once weekly (8 doses), twice monthly (8 doses), and monthly for up to 24 months. End points included safety, efficacy, and pharmacokinetics. Results No maximum tolerated dose was identified in part 1. In part 2, the median time since diagnosis was 5.7 years. Patients had received a median of four prior treatments; 79% of the patients had disease that was refractory to the last therapy received (64% had disease refractory to proteasome inhibitors and immunomodulatory drugs and 64% had disease refractory to bortezomib and lenalidomide), and 76% had received autologous stem-cell transplants. Infusion-related reactions in part 2 were mild (71% of patients had an event of any grade, and 1% had an event of grade 3), with no dose-dependent adverse events. The most common adverse events of grade 3 or 4 (in ≥5% of patients) were pneumonia and thrombocytopenia. The overall response rate was 36% in the cohort that received 16 mg per kilogram (15 patients had a partial response or better, including 2 with a complete response and 2 with a very good partial response) and 10% in the cohort that received 8 mg per kilogram (3 had a partial response). In the cohort that received 16 mg per kilogram, the median progression-free survival was 5.6 months (95% confidence interval [CI], 4.2 to 8.1), and 65% (95% CI, 28 to 86) of the patients who had a response did not have progression at 12 months. Conclusions Daratumumab monotherapy had a favorable safety profile and encouraging efficacy in patients with heavily pretreated and refractory myeloma. (Funded by Janssen Research and Development and Genmab; ClinicalTrials.gov number, NCT00574288 .).
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| 39. |
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| 40. |
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| 41. |
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| 43. |
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| 44. |
- Sokolski, Mateusz, et al.
(författare)
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Phenotype clustering of hospitalized high-risk patients with COVID-19-a machine learning approach within the multicentre, multinational PCHF-COVICAV registry
- 2024
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Ingår i: CARDIOLOGY JOURNAL. - 1897-5593 .- 1898-018X.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The high-risk population of patients with cardiovascular (CV) disease or risk factors (RF) suffering from COVID-19 is heterogeneous. Several predictors for impaired prognosis have been identified. However, with machine learning (ML) approaches, certain phenotypes may be confined to classify the affected population and to predict outcome. This study aimed to phenotype patients using unsupervised ML technique within the International Postgraduate Course Heart Failure Registry for patients hospitalized with COVID-19 and Cardiovascular disease and/or RF (PCHF-COVICAV). Material and methods: Patients from the eight centres with follow-up data available from the PCHF-COVICAV registry were included in this ML analysis (K-medoids algorithm). Results: Out of 617 patients included into the prospective part of the registry, 458 [median age: 76 (IQR:65-84) years, 55% male] were analyzed and 46 baseline variables, including demographics, clinical status, comorbidities and biochemical characteristics were incorporated into the ML. Three clusters were extracted by this ML method. Cluster 1 (n = 181) represents mainly women with the least number of overall comorbidities and cardiovascular RF. Cluster 2 (n = 227) is characterized mainly by men with non-CV conditions and less severe symptoms of infection. Cluster 3 (n = 50) mainly represents men with the highest prevalence of cardiac comorbidities and RF, more extensive inflammation and organ dysfunction with the highest 6-month all-cause mortality risk. Conclusions: The ML process has identified three important clinical clusters from hospitalized COVID-19 CV and/or RF patients. The cluster of males with severe CV disease, particularly HF, and multiple RF presenting with increased inflammation had a particularly poor outcome.
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| 45. |
- Stegmayr, Bernd G, et al.
(författare)
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Panorama of adverse events during cytapheresis
- 2013
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Ingår i: Transfusion and apheresis science. - : Pergamon Press. - 1473-0502 .- 1878-1683. ; 48:2, s. 155-156
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 46. |
- Toussaint, Laura, et al.
(författare)
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Clinical practice in European centres treating paediatric posterior fossa tumours with pencil beam scanning proton therapy
- 2024
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Ingår i: RADIOTHERAPY AND ONCOLOGY. - 0167-8140 .- 1879-0887. ; 198
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: As no guidelines for pencil beam scanning (PBS) proton therapy (PT) of paediatric posterior fossa (PF) tumours exist to date, this study investigated planning techniques across European PT centres, with special considerations for brainstem and spinal cord sparing. Materials and methods: A survey and a treatment planning comparison were initiated across nineteen European PBS-PT centres treating paediatric patients. The survey assessed all aspects of the treatment chain, including but not limited to delineations, dose constraints and treatment planning. Each centre planned two PF tumour cases for focal irradiation, according to their own clinical practice but based on common delineations. The prescription dose was 54 Gy(RBE) for Case 1 and 59.4 Gy (RBE) for Case 2. For both cases, planning strategies and relevant dose metrics were compared. Results: Seventeen (89 %) centres answered the survey, and sixteen (80 %) participated in the treatment planning comparison. In the survey, thirteen (68 %) centres reported using the European Particle Therapy Network definition for brainstem delineation. In the treatment planning study, while most centres used three beam directions, their configurations varied widely across centres. Large variations were also seen in brainstem doses, with a brainstem near maximum dose (D2%) ranging from 52.7 Gy(RBE) to 55.7 Gy(RBE) (Case 1), and from 56.8 Gy(RBE) to 60.9 Gy(RBE) (Case 2). Conclusion: This study assessed the European PBS-PT planning of paediatric PF tumours. Agreement was achieved in e.g. delineation-practice, while wider variations were observed in planning approach and consequently dose to organs at risk. Collaboration between centres is still ongoing, striving towards common guidelines.
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| 47. |
- Werner, Mads, et al.
(författare)
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Arthroscopic knee surgery does not modify hyperalgesic responses to heat injury
- 2003
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Ingår i: Anesthesiology. - 1528-1175. ; 99:5, s. 1152-1157
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Tidskriftsartikel (refereegranskat)abstract
- Background: Experimental studies suggest that surgical injury may up- or down-regulate nociceptive function. Therefore, the aim of this clinical study was to evaluate the effect of elective arthroscopically assisted knee surgery on nociceptive responses to a heat injury. Methods: Seventeen patients scheduled to undergo repair of the anterior cruciate ligament and 16 healthy controls were studied. The first burn injury was induced 6 days before surgery, and the second burn was induced I day after surgery with a contact thermode (12.5 cm(2), 47degreesC for 7 min) placed on the medial aspect of the calf contralateral to the surgical side. Ibuprofen and acetaminophen were given for 2 days before the first burn injury and again from the time of surgery. in the controls, the two burn injuries were separated by 7 days. Sensory variables included cumulated pain score during induction of the burn (visual analog scale), secondary hyperalgesia area, and mechanical and thermal pain perception and pain thresholds assessed before and I h after the burn injury. Results: The heat injuries induced significant increases in pain perception (P < 0.001) and decreases in pain thresholds (P < 0.02). Baseline heat pain thresholds were higher during the second burn injury in patients (P < 0.001) and controls (P < 0.01). However, there were no significant differences in pain to heat injury (P > 0.8), secondary hyperalgesia areas (P > 0.1), mechanical and thermal pain perception (P > 0.1), or mechanical and thermal pain thresholds (P > 0.08) in the burn area before surgery compared to after surgery. Conclusion: Arthroscopic knee surgery did not modify nociceptive responses to a contralaterally applied experimental burn injury.
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