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1.
Reference intervals for reticulocyte hemoglobin content in healthy infants.
Löfving, A, Domellöf, M, Hellström-Westas, L, Andersson, O
Pediatric research. 2018;(5):657-661
Abstract
OBJECTIVES Iron deficiency anemia in childhood is a serious public health problem worldwide. Reticulocyte hemoglobin content (Ret-He) is a novel biomarker of iron deficiency adopted for adults but there is a lack of reference intervals for Ret-He in infants. The aim of this study was to provide data from healthy infants. METHODS Swedish infants (n = 456), born at term after normal pregnancies were included. Ret-He was measured at birth (umbilical cord sample), 48-72 h, 4 months, and 12 months. Reference intervals were calculated as ±2 standard deviations from the mean of Ret-He. RESULTS Reference intervals for newborn Ret-He were 27.4 to 36.0 pg/L (N = 376) in the cord sample, 28.1-37.7 pg/L (N = 253) at 48-72 h, 25.6-33.4 pg/L (N = 341) at four months and 24.9-34.1 pg/L (N = 288) at 12 months. Ret-He was significantly lower among iron-deficient infants, at 4 months mean difference (95% CI) -4.2 pg/L (-6.1 to -2.4) and at 12 months mean difference (95% CI) -3.4 pg/L (-5.0 to -1.8). CONCLUSIONS This longitudinal study presents Ret-He reference intervals based on non-anemic and non-iron-deficient infants and constitutes a step towards standardizing Ret-He as a pre-anemia biomarker of iron deficiency in children.
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2.
Biomarkers of GH action in children and adults.
Schilbach, K, Olsson, DS, Boguszewski, MCS, Bidlingmaier, M, Johannsson, G, Jørgensen, JL
Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. 2018;:1-8
Abstract
Growth hormone (GH) and IGF-I levels in serum are used as biomarkers in the diagnosis and management of GH-related disorders but have not been subject to structured validation. Auxological parameters in children and changes in body composition in adults, as well as metabolic parameters and patient related outcomes are used as clinical and surrogate endpoints. New treatment options, such as long acting GH and GH antagonists, require reevaluation of the currently used biochemical biomarkers. This article will review biomarkers, surrogate endpoints and clinical endpoints related to GH treatment in children and adults as well as in acromegaly.
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Relationship of cardiac biomarkers with white matter hyperintensities in cardioembolic stroke due to atrial fibrillation and/or rheumatic heart disease.
Wei, C, Zhang, S, Liu, J, Yuan, R, Liu, M
Medicine. 2018;(33):e11892
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Abstract
White matter hyperintensities (WMHs), which are common in elderly people and contribute to age-related disability, can coexist with cardiac injury. It remains unclear whether cardiac biomarkers are associated with WMHs.To investigate this question, we prospectively recruited patients with cardioembolic stroke due to atrial fibrillation (AF) and/or rheumatic heart disease (RHD). Four cardiac biomarkers were measured: myoglobin, high-sensitivity cardiac troponin T (hs-cTnT), creatine kinase-MB, and terminal pro-brain natriuretic peptide. WMHs in periventricular and deep white matter were assessed separately.In the entire sample of 171 patients, 120 (70.2%) presented with WMHs, of whom 18 (10.5%) presented with moderate to severe deep white matter hyperintensities (DWMH) and 55 (32.2%) presented with moderate to severe periventricular hyperintensities (PVH). Risk of moderate to severe PVH, after adjusting for confounders, was 2.460-fold higher in patients with high myoglobin levels than in those with low levels, and the risk was 2.608-fold higher in patients with high hs-cTnT levels than in those with low levels. There were no significant associations between any of the 4 cardiac biomarkers and moderate to severe DWMH.This prospective observational study provides new evidence of the potential relationship of cardiac biomarkers with WMHs in patients with cardioembolic stroke due to AF and/or RHD. We found that elevated myoglobin levels and high hs-TnT levels were independently associated with the presence of moderate to severe PVH. Further studies are required to test our findings and explore whether cardiac biomarkers contribute directly to WMHs pathogenesis.
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Comparison of statin plus ezetimibe with double-dose statin on lipid profiles and inflammation markers.
Wu, NQ, Guo, YL, Zhu, CG, Gao, Y, Zhao, X, Sun, D, Sun, J, Xu, RX, Liu, G, Dong, Q, et al
Lipids in health and disease. 2018;(1):265
Abstract
BACKGROUND Achievement of low-density lipoprotein cholesterol (LDL-C) goal is the most important for the patients with atherosclerotic cardiovascular diseases (ASCVD) who received lipid-lowering therapy. It is unclear that whether combination of ezetimibe with statin is superior to double-dose of statin regarding both of the lipid-lowering efficacy and improvement of inflammation in Chinese patients with ASCVD. Therefore, this study was performed to compare the effects of these two regimes on lipid profiles and inflammation markers. METHODS In this randomized control study, ninety eight patients with ASCVD, who were naïve to statins or other lipid-lowering agents, were enrolled into the study, and randomly assigned into two groups, A40 group (atorvastatin 40 mg/d, n = 50), A20E10 group (atorvastatin 20 mg/d combined with ezetimibe 10 mg/d, n = 48).The patients were followed up at week 4 and week 12 after treatment. The lipid profiles and oxidative low-density lipoprotein cholesterol (ox-LDL) were measured at the end of study. RESULTS There were no differences in clinical characteristics including lipid, ox-LDL and hypersensitive C reactive protein (Hs-CRP) among groups at baseline. However, the average level of LDL-C was lower in group A20E10 than that in group A40 significantly (1.59 ± 0.44 mmol/L vs 1.99 ± 0.56 mmol/L, p = 0.001) during follow-up at week 12 after treatment. Importantly, the higher rate of achievement of LDL-C goal was attained at group of combination statin with ezetimibe (79.2% in group A20E10 vs 50.0% in group A40, p = 0.016). The difference of the level of ox-LDL between both the groups after 12 weeks treatment had not statistical significance (3.63 ± 1.13 U/L in group A20E10 vs 4.14 ± 1.32 U/L in group A40, p = 0.077).Similarly, the level of Hs-CRP between both the groups after treatment was not significantly different (p > 0.05). CONCLUSIONS In this randomized study, the data showed that a combination of moderate statin and ezetimibe achieved more reduction of LDL-C compared to the double-dose statin but similar impact on inflammation markers.
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Estimated Glomerular Filtration Rate From a Panel of Filtration Markers-Hope for Increased Accuracy Beyond Measured Glomerular Filtration Rate?
Inker, LA, Levey, AS, Coresh, J
Advances in chronic kidney disease. 2018;(1):67-75
Abstract
The recent Kidney Disease Improving Global Outcomes 2012 CKD guidelines recommend estimating GFR from serum creatinine (eGFRcr) as a first-line test to assess kidney function and using cystatin C or measured glomerular filtration rate (GFR) as confirmatory tests. eGFRcr may be inaccurate in people with variation in muscle mass or diet, and eGFRcys is not more accurate than eGFRcr. eGFRcrcys is more accurate than either, but it is not independent of eGFRcr. Measured GFR is not practical and is susceptible to error due to variation in clearance methods and in the behavior of exogenous filtration markers. Over the past few years, we have hypothesized, and begun to test the hypothesis, that a panel of filtration markers (panel eGFR) from a single blood draw would require fewer demographic or clinical variables and could estimate GFR as accurately as measured GFR. In this article, we describe the conceptual background and rationale for this hypothesis and summarize our work thus far including evaluation of novel low-molecular-weight proteins and metabolites and then outline how we envision that such a panel could be used in clinical practice, research, and public health.
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Vitamin K1 Supplementation Did Not Alter Inflammatory Markers and Clinical Status in Patients with Rheumatoid Arthritis.
Shishavan, NG, Gargari, BP, Jafarabadi, MA, Kolahi, S, Haggifar, S, Noroozi, S
International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition. 2018;(5-6):251-257
Abstract
Background: Rheumatoid arthritis (RA) is an inflammatory disorder in which the disease severity might be decreased by anti-inflammatory agents. There are several lines of evidence which support anti-inflammatory effects of vitamin K. The aim of this study was to examine whether vitamin K is a useful strategy for reducing inflammation in RA subjects. Materials and methods: In this double-blind placebo controlled trial, 58 patients with definitive RA were randomly allocated into two groups to receive vitamin K1 as phylloquinone [10 mg/day] or placebo pills for 8 weeks. Clinical status using disease activity score-28 (DAS-28) and serum concentrations of some inflammatory markers (IL-6, hs-CRP, TNFα) were assessed at baseline and at the end of intervention. Results: There were no significant differences between the two groups regarding any of the baseline characteristics. In the vitamin K1 group, a 27 % decrease in serum levels of IL-6 (P = 0.006) and a 13 % decrease in DAS-28 (P = 0.041) were observed. However, after adjusting for relevant confounders, i. e.; duration of RA, intake of folic acid supplements, energy intake, weight and baseline values of each variable, by comparing the two groups, we found no significant reduction in these markers. Conclusion: Vitamin K1 supplementation at 10 mg/day for 8 weeks had no significant effects on blood biomarkers of inflammation and disease severity of patients with rheumatoid arthritis compared with the placebo group.
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Innovative Use of Novel Biomarkers to Improve the Safety of Renally Eliminated and Nephrotoxic Medications.
Barreto, EF, Rule, AD, Voils, SA, Kane-Gill, SL
Pharmacotherapy. 2018;(8):794-803
Abstract
Over the last decade, the discovery of novel renal biomarkers and research on their use to improve medication effectiveness and safety has expanded considerably. Pharmacists are uniquely positioned to leverage this new technology for renal assessment to improve medication dosing and monitoring. Serum cystatin C is a relatively new, inexpensive, functional renal biomarker that responds more quickly to changing renal function than creatinine and is not meaningfully affected by age, sex, skeletal muscle mass, dietary intake, or deconditioning. Cystatin C has been proposed as an adjunct or alternative to creatinine for glomerular filtration rate assessment and estimation of drug clearance. Tissue inhibitor of metalloproteinase-2·insulin-like growth factor-binding protein 7 ([TIMP-2]·[IGFBP7]) is a composite of two damage biomarkers released into the urine at a checkpoint in mitosis when renal cells undergo stress or sense a future risk of damage. Concentrations of [TIMP-2]·[IGFBP7] increase before a rise in serum creatinine is evident, thus providing insightful information for evaluation in the context of other patient data to predict the risk for impending kidney injury. This article provides a brief overview of novel renal biomarkers being used as a mechanism to improve medication safety including a discussion of cystatin C, as part of drug-dosing algorithms and specifically for vancomycin dosing, and the use of [TIMP-2]·[IGFBP7] for risk prediction in acute kidney injury and drug-induced kidney disease. Select cases of clinical experience with novel renal biomarkers are outlined, and lessons learned and future applications are described.
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[Diagnostic and prognostic biomarkers in acute coronary syndrome].
Kuběna, P, Špinar, J, Dastych, M, Lokaj, P, Pařenica, J
Vnitrni lekarstvi. 2018;(12):935-944
Abstract
Acute myocardial infarction (AMI) is an important cause of mortality and morbidity worldwide. Early diagnostics of this disease helps in the appropriate treatment of patients. Great attention is paid to the diagnostic and risk stratification of patients according to circulating biomarkers. There are a lot of scientific publications describing this topic. The aim of this article is to provide a comprehensive overview of the most important and most examined biomarkers in acute coronary syndrome. Meanwhile troponin takes a fundamental place for AMI diagnostic (mostly the high-sensitive methods) in preference to MB-fraction of creatine kinase and myoglobin. The connection to a higher sudden death risk, reinfarcts and heart failure occurring was also proved by many other biomarkers. The most important of them are the natriuretic peptides, the C-reactive protein, the heart fatty acid binding protein, the pregnancy-associated plasma protein-A, CD146, cystatin C, NGAL, copeptin, MR-proadrenomedullin, and the growth differentiation factor-15. More prospective randomized studies are needed for the further use of these other biomarkers in clinical practice.Key words: acute coronary syndrome - biomarkers.
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The role of new adipokines in gestational diabetes mellitus pathogenesis.
Mierzyński, R, Poniedziałek-Czajkowska, E, Dłuski, D, Leszczyńska-Gorzelak, B
Ginekologia polska. 2018;(4):221-26
Abstract
Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition dur-ing pregnancy. Explanation of the GDM pathogenesis is important due to preventing gestational complications. During pregnancy there are significant changes in maternal metabolism. Many of these changes are influenced by different adi-pokines produced in the placenta and adipose tissue. The exact role of adipokines in the pathogenesis of GDM remains still unknown. Several adipokines have been analysed throughout gestation and their levels have been suggested as biomarkers of maternal-perinatal outcomes. Some of them have been postulated as significant in the pathogenesis of pregnancy complications like GDM. This report aims to review some of the recent topics of adipokine research that may be of particular importance in patho-physiology and diagnosis of gestational diabetes mellitus. Because of manuscript length limitations, after thorough literature review and in view of the recent evidence, we focus on the one of the most well-known adipokine: adiponectin, and not so well-studied: nesfatin-1, chemerin, ghrelin, and CTRP 1.
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Oxidative Stress and Inflammation Induced by Environmental and Psychological Stressors: A Biomarker Perspective.
Ghezzi, P, Floridi, L, Boraschi, D, Cuadrado, A, Manda, G, Levic, S, D'Acquisto, F, Hamilton, A, Athersuch, TJ, Selley, L
Antioxidants & redox signaling. 2018;(9):852-872
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Abstract
SIGNIFICANCE The environment can elicit biological responses such as oxidative stress (OS) and inflammation as a consequence of chemical, physical, or psychological changes. As population studies are essential for establishing these environment-organism interactions, biomarkers of OS or inflammation are critical in formulating mechanistic hypotheses. Recent Advances: By using examples of stress induced by various mechanisms, we focus on the biomarkers that have been used to assess OS and inflammation in these conditions. We discuss the difference between biomarkers that are the result of a chemical reaction (such as lipid peroxides or oxidized proteins that are a result of the reaction of molecules with reactive oxygen species) and those that represent the biological response to stress, such as the transcription factor NRF2 or inflammation and inflammatory cytokines. CRITICAL ISSUES The high-throughput and holistic approaches to biomarker discovery used extensively in large-scale molecular epidemiological exposome are also discussed in the context of human exposure to environmental stressors. FUTURE DIRECTIONS We propose to consider the role of biomarkers as signs and to distinguish between signs that are just indicators of biological processes and proxies that one can interact with and modify the disease process. Antioxid. Redox Signal. 28, 852-872.