| 21. |
- Carrera, Caty, et al.
(författare)
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Validation of a clinical-genetics score to predict hemorrhagic transformations after rtPA.
- 2019
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Ingår i: Neurology. - 1526-632X. ; 93:9, s. e851-e863
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Tidskriftsartikel (refereegranskat)abstract
- To validate the Genot-PA score, a clinical-genetic logistic regression score that stratifies the thrombolytic therapy safety, in a new cohort of patients with stroke.We enrolled 1,482 recombinant tissue plasminogen activator (rtPA)-treated patients with stroke in Spain and Finland from 2003 to 2016. Cohorts were analyzed on the basis of ethnicity and therapy: Spanish patients treated with IV rtPA within 4.5 hours of onset (cohort A and B) or rtPA in combination with mechanical thrombectomy within 6 hours of onset (cohort C) and Finnish participants treated with IV rtPA within 4.5 hours of onset (cohort D). The Genot-PA score was calculated, and hemorrhagic transformation (HT) and parenchymal hematoma (PH) risks were determined for each score stratum.Genot-PA score was tested in 1,324 (cohort A, n = 726; B, n = 334; C, n = 54; and D, n = 210) patients who had enough information to complete the score. Of these, 213 (16.1%) participants developed HT and 85 (6.4%) developed PH. In cohorts A, B, and D, HT occurrence was predicted by the score (p = 2.02 × 10-6, p = 0.023, p = 0.033); PH prediction was associated in cohorts A through C (p = 0.012, p = 0.034, p = 5.32 × 10-4). Increased frequency of PH events from the lowest to the highest risk group was found (cohort A 4%-15.7%, cohort B 1.5%-18.2%, cohort C 0%-100%). The best odds ratio for PH prediction in the highest-risk group was obtained in cohort A (odds ratio 5.16, 95% confidence interval 1.46-18.08, p = 0.009).The Genot-PA score predicts HT in patients with stroke treated with IV rtPA. Moreover, in an exploratory study, the score was associated with PH risk in mechanical thrombectomy-treated patients.
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| 22. |
- Huybrechts, Inge, et al.
(författare)
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Characterization of the degree of food processing in the European prospective investigation into cancer and nutrition : application of the nova classification and validation using selected biomarkers of food processing
- 2022
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Ingår i: Frontiers in Nutrition. - : Frontiers Media S.A.. - 2296-861X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiological studies have demonstrated an association between the degree of food processing in our diet and the risk of various chronic diseases. Much of this evidence is based on the international Nova classification system, which classifies food into four groups based on the type of processing: (1) Unprocessed and minimally processed foods, (2) Processed culinary ingredients, (3) Processed foods, and (4) “Ultra-processed” foods (UPF). The ability of the Nova classification to accurately characterise the degree of food processing across consumption patterns in various European populations has not been investigated so far. Therefore, we applied the Nova coding to data from the European Prospective Investigation into Cancer and Nutrition (EPIC) in order to characterize the degree of food processing in our diet across European populations with diverse cultural and socio-economic backgrounds and to validate this Nova classification through comparison with objective biomarker measurements.Methods: After grouping foods in the EPIC dataset according to the Nova classification, a total of 476,768 participants in the EPIC cohort (71.5% women; mean age 51 [standard deviation (SD) 9.93]; median age 52 [percentile (p)25–p75: 58–66] years) were included in the cross-sectional analysis that characterised consumption patterns based on the Nova classification. The consumption of food products classified as different Nova categories were compared to relevant circulating biomarkers denoting food processing, measured in various subsamples (N between 417 and 9,460) within the EPIC cohort via (partial) correlation analyses (unadjusted and adjusted by sex, age, BMI and country). These biomarkers included an industrial transfatty acid (ITFA) isomer (elaidic acid; exogenous fatty acid generated during oil hydrogenation and heating) and urinary 4-methyl syringol sulfate (an indicator for the consumption of smoked food and a component of liquid smoke used in UPF).Results: Contributions of UPF intake to the overall diet in % grams/day varied across countries from 7% (France) to 23% (Norway) and their contributions to overall % energy intake from 16% (Spain and Italy) to >45% (in the UK and Norway). Differences were also found between sociodemographic groups; participants in the highest fourth of UPF consumption tended to be younger, taller, less educated, current smokers, more physically active, have a higher reported intake of energy and lower reported intake of alcohol. The UPF pattern as defined based on the Nova classification (group 4;% kcal/day) was positively associated with blood levels of industrial elaidic acid (r = 0.54) and 4-methyl syringol sulfate (r = 0.43). Associations for the other 3 Nova groups with these food processing biomarkers were either inverse or non-significant (e.g., for unprocessed and minimally processed foods these correlations were –0.07 and –0.37 for elaidic acid and 4-methyl syringol sulfate, respectively).Conclusion: These results, based on a large pan-European cohort, demonstrate sociodemographic and geographical differences in the consumption of UPF. Furthermore, these results suggest that the Nova classification can accurately capture consumption of UPF, reflected by stronger correlations with circulating levels of industrial elaidic acid and a syringol metabolite compared to diets high in minimally processed foods.
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| 23. |
- Insausti, Ricardo, et al.
(författare)
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Ex vivo, in situ perfusion protocol for human brain fixation compatible with microscopy, MRI techniques, and anatomical studies
- 2023
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Ingår i: Frontiers in Neuroanatomy. - : Frontiers Media SA. - 1662-5129. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- We present a method for human brain fixation based on simultaneous perfusion of 4% paraformaldehyde through carotids after a flush with saline. The left carotid cannula is used to perfuse the body with 10% formalin, to allow further use of the body for anatomical research or teaching. The aim of our method is to develop a vascular fixation protocol for the human brain, by adapting protocols that are commonly used in experimental animal studies. We show that a variety of histological procedures can be carried out (cyto- and myeloarchitectonics, histochemistry, immunohistochemistry, intracellular cell injection, and electron microscopy). In addition, ex vivo, ex situ high-resolution MRI (9.4T) can be obtained in the same specimens. This procedure resulted in similar morphological features to those obtained by intravascular perfusion in experimental animals, provided that the postmortem interval was under 10 h for several of the techniques used and under 4 h in the case of intracellular injections and electron microscopy. The use of intravascular fixation of the brain inside the skull provides a fixed whole human brain, perfectly fitted to the skull, with negligible deformation compared to conventional techniques. Given this characteristic of ex vivo, in situ fixation, this procedure can probably be considered the most suitable one available for ex vivo MRI scans of the brain. We describe the compatibility of the method proposed for intravascular fixation of the human brain and fixation of the donor’s body for anatomical purposes. Thus, body donor programs can provide human brain tissue, while the remainder of the body can also be fixed for anatomical studies. Therefore, this method of human brain fixation through the carotid system optimizes the procurement of human brain tissue, allowing a greater understanding of human neurological diseases, while benefiting anatomy departments by making the remainder of the body available for teaching purposes.
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| 24. |
- Ordoñez, Carlos A., et al.
(författare)
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REBOA as a New Damage Control Component in Hemodynamically Unstable Noncompressible Torso Hemorrhage Patients
- 2020
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Ingår i: Colombia Médica. - : Corporacion Editora Medica del Valle. - 0120-8322 .- 1657-9534. ; 51:4
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Tidskriftsartikel (refereegranskat)abstract
- Noncompressible torso hemorrhage is one of the leading causes of preventable death worldwide. An efficient and appropriate evaluation of the trauma patient with ongoing hemorrhage is essential to avoid the development of the lethal diamond (hypothermia, coagulopathy, hypocalcemia, and acidosis). Currently, the initial management strategies include permissive hypotension, hemostatic resuscitation, and damage control surgery. However, recent advances in technology have opened the doors to a wide variety of endovascular techniques that achieve these goals with minimal morbidity and limited access. An example of such advances has been the introduction of the Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA), which has received great interest among trauma surgeons around the world due to its potential and versatility in areas such as trauma, gynecology & obstetrics and gastroenterology. This article aims to describe the experience earned in the use of REBOA in noncompressible torso hemorrhage patients. Our results show that REBOA can be used as a new component in the damage control resuscitation of the severely injured trauma patient. To this end, we propose two new deployment algorithms for hemodynamically unstable noncompressible torso hemorrhage patients: one for blunt and another for penetrating trauma. We acknowledge that REBOA has its limitations, which include a steep learning curve, its inherent cost and availability. Although to reach the best outcomes with this new technology, it must be used in the right way, by the right surgeon with the right training and to the right patient.
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| 25. |
- Radchuk, Viktoriia, et al.
(författare)
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Adaptive responses of animals to climate change are most likely insufficient
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Biological responses to climate change have been widely documented across taxa and regions, but it remains unclear whether species are maintaining a good match between phenotype and environment, i.e. whether observed trait changes are adaptive. Here we reviewed 10,090 abstracts and extracted data from 71 studies reported in 58 relevant publications, to assess quantitatively whether phenotypic trait changes associated with climate change are adaptive in animals. A meta-analysis focussing on birds, the taxon best represented in our dataset, suggests that global warming has not systematically affected morphological traits, but has advanced phenological traits. We demonstrate that these advances are adaptive for some species, but imperfect as evidenced by the observed consistent selection for earlier timing. Application of a theoretical model indicates that the evolutionary load imposed by incomplete adaptive responses to ongoing climate change may already be threatening the persistence of species.
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| 26. |
- Sharma, Mukul, et al.
(författare)
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Safety and efficacy of factorXIa inhibition with milvexian for secondary stroke prevention (AXIOMATIC-SSP) : a phase 2, international, randomised, double-blind, placebo-controlled, dose-finding trial
- 2024
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Ingår i: LANCET NEUROLOGY. - 1474-4422 .- 1474-4465. ; 23:1, s. 46-59
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Tidskriftsartikel (refereegranskat)abstract
- Background People with factor XI deficiency have lower rates of is chaemic stroke than the general population and infrequent spontaneous bleeding, suggesting that factor XI has a more important role in thrombosis than in haemostasis. Milvexian, an oral small-molecule inhibitor of activated factor XI, added to standard antiplatelet therapy, might reduce the risk of non-cardioembolic ischaemic stroke without increasing the risk of bleeding. We aimed to estimate the dose-response of milvexian for recurrent ischaemic cerebral events and major bleeding in patients with recent ischaemic stroke or transient ischaemic attack (TIA).Methods AXIOMATIC-SSP was a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial done at 367 hospitals in 27 countries. Eligible participants aged 40 years or older, with acute (<48 h) ischaemic stroke or high-risk TIA, were randomly assigned by a web-based interactive response system in a 1:1:1:1:1:2 ratio to receive one of five doses of milvexian (25 mg once daily, 25 mg twice daily, 50 mg twice daily, 100 mg twice daily, or 200 mg twice daily) or matching placebo twice daily for 90 days. All participants received clopidogrel 75 mg daily for the first 21 days and aspirin 100 mg daily for the first 90 days. Investigators, site staff, and participants were masked to treatment assignment. The primary efficacy endpoint was the composite of ischaemic stroke or incident covert brain infarct on MRI at 90 days, assessed in all participants allocated to treatment who completed a follow-up MRI brain scan, and the primary analysis assessed the dose-response relationship with Multiple Comparison Procedure-Modelling (MCP-MOD). The main safety outcome was major bleeding at 90 days, assessed in all participants who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov (NCT03766581) and the EU Clinical Trials Register (2017-005029-19).Findings Between Jan 27, 2019, and Dec 24, 2021, 2366 participants were randomly allocated to placebo (n=691); milvexian 25 mg once daily (n=328); or twice-daily doses of milvexian 25 mg (n=318), 50 mg (n=328), 100 mg (n=310), or 200 mg (n=351). The median age of participants was 71 (IQR 62-77) years and 859 (36%) were female. At 90 days, the estimates of the percentage of participants with either symptomatic ischaemic stroke or covert brain infarcts were 168 (902% CI 145-191) for placebo, 167 (148-186) for 25 mg milvexian once daily, 166 (148-183) for 25 mg twice daily, 156 (139-175) for 50 mg twice daily, 154 (134-176) for 100 mg twice daily, and 153 (128-197) for 200 mg twice daily. No significant dose-response was observed among the five milvexian doses for the primary composite efficacy outcome. Model-based estimates of the relative risk with milvexian compared with placebo were 099 (902% CI 091-105) for 25 mg once daily, 099 (087-111) for 25 mg twice daily, 093 (078-111) for 50 mg twice daily, 092 (075-113) for 100 mg twice daily, and 091 (072-126) for 200 mg twice daily. No apparent dose-response was observed for major bleeding (four [1%] of 682 participants with placebo, two [1%] of 325 with milvexian 25 mg once daily, two [1%] of 313 with 25 mg twice daily, five [2%] of 325 with 50 mg twice daily, five [2%] of 306 with 100 mg twice daily, and five [1%] of 344 with 200 mg twice daily). Five treatment-emergent deaths occurred, four of which were considered unrelated to the study drug by the investigator.Interpretation Factor XIa inhibition with milvexian, added to dual antiplatelet therapy, did not substantially reduce the composite outcome of symptomatic ischaemic stroke or covert brain infarction and did not meaningfully increase the risk of major bleeding. Findings from our study have informed the design of a phase 3 trial of milvexian for the prevention of ischaemic stroke in patients with acute ischaemic stroke or TIA.
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| 27. |
- Steffen, Annika, et al.
(författare)
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Anthropometry and Esophageal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition
- 2009
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 18:7, s. 2079-2089
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Tidskriftsartikel (refereegranskat)abstract
- Background: Increasing evidence suggests that general obesity [measured by body mass index (BMI)] is positively associated with risk of esophageal adenocarcinoma (EAC). In contrast, previous studies have shown inverse relations with esophageal squamous cell carcinoma (ESCC). However, it is still unclear whether body fat distribution, particularly abdominal obesity, is associated with each type of esophageal cancer. Methods: We applied multivariable adjusted Cox proportional hazards regression to investigate the association between anthropometric measures and risk of EAC and ESCC among 346,554 men and women participating in the European Prospective Investigation into Cancer and Nutrition. All statistical tests were two sided. Results: During 8.9 years of follow-up, we documented 88 incident cases of EAC and 110 cases of ESCC. BMI, waist circumference, and waist-to-hip ratio (WHR) were positively associated with EAC risk [highest versus lowest quintile; relative risk (RR), 2.60; 95% confidence interval (95% CI), 1.23-5.51; P-trend < 0.01; RR, 3.07; 95% CI, 1.35-6.98; P-trend < 0.003; and RR, 2.12; 95% CI, 0.98-4.57; P-trend < 0.004]. In contrast, BMI and waist circumference were inversely related to ESCC risk, whereas WHR showed no association with ESCC. In stratified analyses, BMI and waist circumference were significantly inversely related to ESCC only among smokers but not among nonsmokers. However, when controlled for BMI, we found positive associations for waist circumference and WHR with ESCC, and these associations were observed among smokers and nonsmokers. Conclusion: General and abdominal obesity were associated with higher EAC risk. Further, our study suggests that particularly an abdominal body fat distribution might also be a risk factor for ESCC. (Cancer Epidemiol Biomarkers Prev 2009;18(7):2079-89)
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| 28. |
- Vermeulen, Esther, et al.
(författare)
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Dietary Flavonoid Intake and Esophageal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition Cohort
- 2013
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 178:4, s. 570-581
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Tidskriftsartikel (refereegranskat)abstract
- We prospectively investigated dietary flavonoid intake and esophageal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 477,312 adult subjects from 10 European countries. At baseline, country-specific validated dietary questionnaires were used. During a mean follow-up of 11 years (1992-2010), there were 341 incident esophageal cancer cases, of which 142 were esophageal adenocarcinoma (EAC), 176 were esophageal squamous cell carcinoma (ESCC), and 23 were other types of esophageal cancer. In crude models, a doubling in total dietary flavonoid intake was inversely associated with esophageal cancer risk (hazard ratio (HR) (log(2))=0.87, 95% confidence interval (CI): 0.78, 0.98) but not in multi-variable models (HR (log(2))=0.97, 95% CI: 0.86, 1.10). After covariate adjustment, no statistically significant association was found between any flavonoid subclass and esophageal cancer, EAC, or ESCC. However, among current smokers, flavonols were statistically significantly associated with a reduced esophageal cancer risk (HR (log(2)) = 0.72, 95% CI: 0.56, 0.94), whereas total flavonoids, flavanols, and flavan-3-ol monomers tended to be inversely associated with esophageal cancer risk. No associations were found in either never or former smokers. These findings suggest that dietary flavonoid intake was not associated with overall esophageal cancer, EAC, or ESCC risk, although total flavonoids and some flavonoid subclasses, particularly flavonols, may reduce the esophageal cancer risk among current smokers.
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| 29. |
- Zamora-Ros, Raul, et al.
(författare)
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Dietary flavonoid and lignan intake and breast cancer risk according to menopause and hormone receptor status in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study
- 2013
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 139:1, s. 163-176
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Tidskriftsartikel (refereegranskat)abstract
- Evidence on the association between dietary flavonoids and lignans and breast cancer (BC) risk is inconclusive, with the possible exception of isoflavones in Asian countries. Therefore, we investigated prospectively dietary total and subclasses of flavonoid and lignan intake and BC risk according to menopause and hormonal receptor status in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 334,850 women, mostly aged between 35 and 70 years from ten European countries. At baseline, country-specific validated dietary questionnaires were used. A flavonoid and lignan food composition database was developed from the US Department of Agriculture, the Phenol-Explorer and the UK Food Standards Agency databases. Cox regression models were used to analyse the association between dietary flavonoid/lignan intake and the risk of developing BC. During an average 11.5-year follow-up, 11,576 incident BC cases were identified. No association was observed between the intake of total flavonoids [hazard ratio comparing fifth to first quintile (HRQ5-Q1) 0.97, 95 % confidence interval (CI): 0.90-1.04; P trend = 0.591], isoflavones (HRQ5-Q1 1.00, 95 % CI: 0.91-1.10; P trend = 0.734), or total lignans (HRQ5-Q1 1.02, 95 % CI: 0.93-1.11; P trend = 0.469) and overall BC risk. The stratification of the results by menopausal status at recruitment or the differentiation of BC cases according to oestrogen and progesterone receptors did not affect the results. This study shows no associations between flavonoid and lignan intake and BC risk, overall or after taking into account menopausal status and BC hormone receptors.
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| 30. |
- Zamora-Ros, Raul, et al.
(författare)
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Dietary intakes and food sources of phenolic acids in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
- 2013
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Ingår i: British Journal of Nutrition. - : Cambridge University Press. - 1475-2662 .- 0007-1145. ; 110:8, s. 1500-1511
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Tidskriftsartikel (refereegranskat)abstract
- Phenolic acids are secondary plant metabolites that may have protective effects against oxidative stress, inflammation and cancer in experimental studies. To date, limited data exist on the quantitative intake of phenolic acids. We estimated the intake of phenolic acids and their food sources and associated lifestyle factors in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Phenolic acid intakes were estimated for 36 037 subjects aged 35-74 years and recruited between 1992 and 2000 in ten European countries using a standardised 24 h recall software (EPIC-Soft), and their food sources were identified. Dietary data were linked to the Phenol-Explorer database, which contains data on forty-five aglycones of phenolic acids in 452 foods. The total phenolic acid intake was highest in Aarhus, Denmark (1265.5 and 980.7 mg/d in men and women, respectively), while the intake was lowest in Greece (213.2 and 158.6 mg/d in men and women, respectively). The hydroxycinnamic acid subclass was the main contributor to the total phenolic acid intake, accounting for 84.6-95.3% of intake depending on the region. Hydroxybenzoic acids accounted for 4.6-14.4%, hydroxyphenylacetic acids 0.1-0.8% and hydroxyphenylpropanoic acids <= 0.1% for all regions. An increasing south-north gradient of consumption was also found. Coffee was the main food source of phenolic acids and accounted for 55.3-80.7% of the total phenolic acid intake, followed by fruits, vegetables and nuts. A high heterogeneity in phenolic acid intake was observed across the European countries in the EPIC cohort, which will allow further exploration of the associations with the risk of diseases.
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