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- Taddei, C, et al.
(författare)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Tidskriftsartikel (refereegranskat)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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- Quist-Paulsen, P., et al.
(författare)
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T-cell acute lymphoblastic leukemia in patients 1-45 years treated with the pediatric NOPHO ALL2008 protocol
- 2020
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 34:2, s. 347-357
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Tidskriftsartikel (refereegranskat)abstract
- The NOPHO ALL2008 is a population-based study using an unmodified pediatric protocol in patients 1-45 years of age with acute lymphoblastic leukemia. Patients with T-ALL were given a traditional pediatric scheme if fast responding (minimal residual disease (MRD) < 0.1% day 29), or intensive block-based chemotherapy if slow responding (MRD > 0.1% day 29). Both treatment arms included pediatric doses of high-dose methotrexate and asparaginase. If MRD >= 5% on day 29 or >= 0.1% after consolidation, patients were assigned to allogeneic hematopoietic stem cell transplantation. The 5-year overall survival of the 278 T-ALL patients was 0.75 (95% CI 0.69-0.81), being 0.82 (0.74-0.88) for patients 1.0-9.9 years, 0.76 (0.66-0.86) for those 10.0-17.9 years, and 0.65 (0.55-0.75) for the older patients. The risk of death in first remission was significantly higher in adults (12%) compared with the 1-9 years group (4%). The MRD responses in the three age groups were similar, and only a nonsignificant increase in relapse risk was found in adults. In conclusion, an unmodified pediatric protocol in patients 1-45 years is effective in all age groups. The traditional pediatric treatment schedule was safe for all patients, but the intensive block therapy led to a high toxic death rate in adults.
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- Nordstrom, CH, et al.
(författare)
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Bedside interpretation of cerebral energy metabolism utilizing microdialysis in neurosurgical and general intensive care
- 2022
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Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 13, s. 968288-
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Tidskriftsartikel (refereegranskat)abstract
- The microdialysis technique was initially developed for monitoring neurotransmitters in animals. In 1995 the technique was adopted to clinical use and bedside enzymatic analysis of glucose, pyruvate, lactate, glutamate and glycerol. Under clinical conditions microdialysis has also been used for studying cytokines, protein biomarkers, multiplex proteomic and metabolomic analyses as well as for pharmacokinetic studies and evaluation of blood-brain barrier function. This review focuses on the variables directly related to cerebral energy metabolism and the possibilities and limitations of microdialysis during routine neurosurgical and general intensive care. Our knowledge of cerebral energy metabolism is to a large extent based on animal experiments performed more than 40 years ago. However, the different biochemical information obtained from various techniques should be recognized. The basic animal studies analyzed brain tissue homogenates while the microdialysis technique reflects the variables in a narrow zone of interstitial fluid surrounding the probe. Besides the difference of the volume investigated, the levels of the biochemical variables differ in different compartments. During bedside microdialysis cerebral energy metabolism is primarily reflected in measured levels of glucose, lactate and pyruvate and the lactate to pyruvate (LP) ratio. The LP ratio reflects cytoplasmatic redox-state which increases instantaneously during insufficient aerobic energy metabolism. Cerebral ischemia is characterized by a marked increase in intracerebral LP ratio at simultaneous decreases in intracerebral levels of pyruvate and glucose. Mitochondrial dysfunction is characterized by a moderate increase in LP ratio at a very marked increase in cerebral lactate and normal or elevated levels of pyruvate and glucose. The patterns are of importance in particular for interpretations in transient cerebral ischemia. A new technique for evaluating global cerebral energy metabolism by microdialysis of the draining cerebral venous blood is discussed. In experimental studies it has been shown that pronounced global cerebral ischemia is reflected in venous cerebral blood. Jugular bulb microdialysis has been investigated in patients suffering from subarachnoid hemorrhage, during cardiopulmonary bypass and resuscitation after out of hospital cardiac arrest. Preliminary results indicate that the new technique may give valuable information of cerebral energy metabolism in clinical conditions when insertion of an intracerebral catheter is contraindicated.
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- Rank, Cecilie U., et al.
(författare)
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Asparaginase-Associated Pancreatitis in Acute Lymphoblastic Leukemia : Results From the NOPHO ALL2008 Treatment of Patients 1-45 Years of Age
- 2020
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Ingår i: Journal of Clinical Oncology. - Alexandria : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 38:2, s. 145-154
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Asparaginase-associated pancreatitis (AAP) is common in patients with acute lymphoblastic leukemia (ALL), but risk differences across age groups both in relation to first-time AAP and after asparaginase re-exposure have not been explored.PATIENTS AND METHODS: We prospectively registered AAP (n = 168) during treatment of 2,448 consecutive ALL patients aged 1.0-45.9 years diagnosed from July 2008 to October 2018 and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol.RESULTS: Compared with patients aged 1.0-9.9 years, adjusted AAP hazard ratios (HRa) were associated with higher age with almost identical HRa (1.6; 95% CI, 1.1 to 2.3; P = .02) for adolescents (10.0-17.9 years) and adults (18.0-45.9 years). The day 280 cumulative incidences of AAP were 7.0% for children (1.0-9.9 years: 95% CI, 5.4 to 8.6), 10.1% for adolescents (10.0 to 17.9 years: 95% CI, 7.0 to 13.3), and 11.0% for adults (18.0-45.9 years: 95% CI, 7.1 to 14.9; P = .03). Adolescents had increased odds of both acute (odds ratio [OR], 5.2; 95% CI, 2.1 to 13.2; P = .0005) and persisting complications (OR, 6.7; 95% CI, 2.4 to 18.4; P = .0002) compared with children (1.0-9.9 years), whereas adults had increased odds of only persisting complications (OR, 4.1; 95% CI, 1.4 to 11.8; P = .01). Fifteen of 34 asparaginase-rechallenged patients developed a second AAP. Asparaginase was truncated in 17/21 patients with AAP who subsequently developed leukemic relapse, but neither AAP nor the asparaginase truncation was associated with increased risk of relapse.CONCLUSION: Older children and adults had similar AAP risk, whereas morbidity was most pronounced among adolescents. Asparaginase re-exposure should be considered only for patients with an anticipated high risk of leukemic relapse, because multiple studies strongly indicate that reduction of asparaginase treatment intensity increases the risk of relapse.
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