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1.
Calprotectin: from biomarker to biological function.
Jukic, A, Bakiri, L, Wagner, EF, Tilg, H, Adolph, TE
Gut. 2021;(10):1978-1988
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Abstract
The incidence of inflammatory bowel diseases (IBD) emerged with Westernisation of dietary habits worldwide. Crohn's disease and ulcerative colitis are chronic debilitating conditions that afflict individuals with substantial morbidity and challenge healthcare systems across the globe. Since identification and characterisation of calprotectin (CP) in the 1980s, faecal CP emerged as significantly validated, non-invasive biomarker that allows evaluation of gut inflammation. Faecal CP discriminates between inflammatory and non-inflammatory diseases of the gut and portraits the disease course of human IBD. Recent studies revealed insights into biological functions of the CP subunits S100A8 and S100A9 during orchestration of an inflammatory response at mucosal surfaces across organ systems. In this review, we summarise longitudinal evidence for the evolution of CP from biomarker to rheostat of mucosal inflammation and suggest an algorithm for the interpretation of faecal CP in daily clinical practice. We propose that mechanistic insights into the biological function of CP in the gut and beyond may facilitate interpretation of current assays and guide patient-tailored medical therapy in IBD, a concept warranting controlled clinical trials.
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Clinical diagnosis of Alzheimer's disease: recommendations of the International Working Group.
Dubois, B, Villain, N, Frisoni, GB, Rabinovici, GD, Sabbagh, M, Cappa, S, Bejanin, A, Bombois, S, Epelbaum, S, Teichmann, M, et al
The Lancet. Neurology. 2021;(6):484-496
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Abstract
In 2018, the US National Institute on Aging and the Alzheimer's Association proposed a purely biological definition of Alzheimer's disease that relies on biomarkers. Although the intended use of this framework was for research purposes, it has engendered debate and challenges regarding its use in everyday clinical practice. For instance, cognitively unimpaired individuals can have biomarker evidence of both amyloid β and tau pathology but will often not develop clinical manifestations in their lifetime. Furthermore, a positive Alzheimer's disease pattern of biomarkers can be observed in other brain diseases in which Alzheimer's disease pathology is present as a comorbidity. In this Personal View, the International Working Group presents what we consider to be the current limitations of biomarkers in the diagnosis of Alzheimer's disease and, on the basis of this evidence, we propose recommendations for how biomarkers should and should not be used for diagnosing Alzheimer's disease in a clinical setting. We recommend that Alzheimer's disease diagnosis be restricted to people who have positive biomarkers together with specific Alzheimer's disease phenotypes, whereas biomarker-positive cognitively unimpaired individuals should be considered only at-risk for progression to Alzheimer's disease.
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Exploring the highs and lows of very low carbohydrate high fat diets on weight loss and diabetes- and cardiovascular disease-related risk markers: A systematic review.
Ross, LJ, Byrnes, A, Hay, RL, Cawte, A, Musial, JE
Nutrition & dietetics: the journal of the Dietitians Association of Australia. 2021;(1):41-56
Abstract
AIM: Very low carbohydrate high fat diets (VLCHF) are increasingly popular for weight loss and diabetes management, but the risk implications of long-term adherence to a high-fat-diet remain unclear, especially in high-risk populations. This review aimed to examine adherence, weight loss, diabetes- and cardiovascular disease (CVD)-related risk markers in adults consuming VLCHF diets. METHODS Online databases were searched for randomised controlled trials ≥3 months duration that met a pre-defined macronutrient prescription: VLCHF ≤25%E carbohydrate, >35%E fat; low fat (LF) ≥45%E carbohydrate, ≤30%E fat; and reported energy, saturated fat (SFA), weight, blood glucose, cholesterol and blood pressure (BP). Studies were excluded if the macronutrient prescription was not targeted (n = 32); not met (n = 17) or not reported (n = 13). RESULTS Eight studies included: 1217 commenced; 922 completed overweight and obese adults. Diets were isocaloric moderately energy-restricted, closely monitored with ongoing support from dietitians, physicians, and/or nurses. Four studies reported non-adherence beyond 3 months (n = 3) and 6 months (n = 1) despite interventions of 12, 15 and 24 months. VLCHF diets were high in fat and SFA (fat 49%-56%E; SFA 11%-21%E) compared to LF diets (fat 13%-29%E; SFA 5%-11%E). All groups achieved significant weight loss and improvements in BP and blood glucose. LDL-C reduction favoured LF, P < .05; increased HDL-C and reduced triglyceride levels favoured VLCHF, P < .05. CONCLUSIONS VLCHF and LF diets with moderate energy restriction demonstrate similar weight loss and improvements to BP to 3 months. However, adherence is likely poor without intensive support from health professionals. Dietary SFA should be monitored to ensure recommended intakes, but longer-term studies with high adherence are required to confirm the level of CVD-risk and potential harms.
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Do low molecular weight antioxidants contribute to the Protection against oxidative damage? The interrelation between oxidative stress and low molecular weight antioxidants based on data from the MARK-AGE study.
Pinchuk, I, Kohen, R, Stuetz, W, Weber, D, Franceschi, C, Capri, M, Hurme, M, Grubeck-Loebenstein, B, Schön, C, Bernhardt, J, et al
Archives of biochemistry and biophysics. 2021;:109061
Abstract
A redox steady state is important in maintaining vital cellular functions and is therefore homeostatically controlled by a number of antioxidative agents, the most important of which are enzymes. Oxidative Stress (OS) is associated with (or/and caused by) excessive production of damaging reactive oxygen and/or nitrogen species (ROS, RNS), which play a role in many pathologies. Because OS is a risk factor for many diseases, much effort (and money) is devoted to early diagnosis and treatment of OS. The desired benefit of the "identify (OS) and treat (by low molecular weight antioxidants, LMWA)" approach is to enable selective treatment of patients under OS. The present work aims at gaining understanding of the benefit of the antioxidants based on interrelationship between the concentration of different OS biomarkers and LMWA. Both the concentrations of a variety of biomarkers and of LMWA were previously determined and some analyses have been published by the MARK-AGE team. For the sake of simplicity, we assume that the concentration of an OS biomarker is a linear function of the concentration of a LMWA (if the association is due to causal relationship). A negative slope of this dependence (and sign of the correlation coefficient) can be intuitively expected for an antioxidant, a positive slope indicates that the LMWA is pro-oxidative, whereas extrapolation of the OS biomarker to [LMWA] = 0 is an approximation of the concentration of the OS biomarker in the absence of the LMWA. Using this strategy, we studied the effects of 12 LMWA (including tocopherols, carotenoids and ascorbic acid) on the OS status, as observed with 8 biomarkers of oxidative damage (including malondialdehyde, protein carbonyls, 3-nitrotyrosine). The results of this communication show that in a cross-sectional study the LMWA contribute little to the redox state and that different "antioxidants" are very different, so that single LMWA treatment of OS is not scientifically justified assuming our simple model. In view of the difficulty of quantitating the OS and the very different effects of various LMWA, the use of the "identify and treat" approach is questionable.
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Effects of exenatide on urinary albumin in overweight/obese patients with T2DM: a randomized clinical trial.
Kang, C, Qiao, Q, Tong, Q, Bai, Q, Huang, C, Fan, R, Wang, H, Kaliannan, K, Wang, J, Xu, J
Scientific reports. 2021;(1):20062
Abstract
In this study, we investigated the effect of exenatide (EXE), a glucagon-like peptide (GLP)-1 receptor agonist, on kidney function, obesity indices, and glucose control in overweight/obese patients with type 2 diabetes mellitus (T2DM). A total of 159 overweight/obese patients with T2DM were randomized to the EXE group or insulin glargine (GLAR) control group for a total treatment period of 24 weeks. EXE intervention significantly reduced the urine albumin concentration (UAC) at week 12 and 24 endpoints (P < 0.001 at week 12 and 24). The levels of the anthropometric, glucose and lipid parameters (TG and HDL-c), and inflammation biomarkers (CRP and TNF-α) in the EXE group were improved at 12 weeks or 24 weeks, respectively. Meanwhile, a comparison between two groups showed significant changes in anthropometric parameters, glucose parameters, lipid parameters (TG and HDL-c), and Inflammation biomarkers (CRP, IL-6, and TNF-α). Serum fibroblast growth factor 21 (FGF21) was increased in the EXE group (P = 0.005) at week 24, and the change was significantly improved compared with GLAR group (P = 0.003). Correlation network analysis showed that FGF21 had a more central role in improving metabolism in the EXE group, and the change of FGF 21 was significantly negatively correlated with UAC at week 12 and week 24, respectively (r = - 0.297, P = 0.010; r = - 0.294, P = 0.012). Our results showed that EXE could help patients improve UAC, glycemic levels, and inflammatory biomarkers after a follow-up period of 24 weeks intervention. These EXE effects may be partly mediated by FGF 21, indicating that EXE is an effective and safe way to control albuminuria in overweight/obese patients with T2DM.
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Elevated holo-transcobalamin in Gaucher disease type II: A case report.
Basgalupp, SP, Donis, KC, Siebert, M, E Vairo, FP, Artigalas, O, de Camargo Pinto, LL, Behringer, S, Spiekerkoetter, U, Hannibal, L, Schwartz, IVD
American journal of medical genetics. Part A. 2021;(8):2471-2476
Abstract
Gaucher disease (GD), one of the most common lysosomal disorders, is caused by deficiency of β-glucocerebrosidase. Based on the presence and severity of neurological complications, GD is classified into types I, II (the most severe form), and III. Abnormalities in systemic markers of vitamin B12 (B12 ) metabolism have been reported in GD type I patients, suggesting a higher prevalence of B12 deficiency in these patients. A 2-month-old male with GD type II was admitted to the hospital presenting jaundice, hepatosplenomegaly, and ichthyosis. At admission, cholestasis and ascites, abnormal liver function enzymes, prolonged prothrombin time, and high levels of B12 were confirmed. Analysis of biomarkers of B12 status revealed elevated B12 and holo-transcobalamin (holo-TC) levels. The B12 profile found in our patient is the opposite to what is described for GD type I patients. Holo-TC may increase in inflammatory states or due to liver diseases. In GD, the accumulation of glucocerebroside may be a trigger that initiates a systemic inflammatory reaction, characterized by macrophage activation. We suggest higher levels of holo-TC could be associated with a more severe (neuronopathic) GD, and be a biomarker of GD type II.
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Predicting psoriasis using routine laboratory tests with random forest.
Zhou, J, Li, Y, Guo, X
PloS one. 2021;(10):e0258768
Abstract
Psoriasis is a chronic inflammatory skin disease that affects approximately 125 million people worldwide. It has significant impacts on both physical and emotional health-related quality of life comparable to other major illnesses. Accurately prediction of psoriasis using biomarkers from routine laboratory tests has important practical values. Our goal is to derive a powerful predictive model for psoriasis disease based on only routine hospital tests. We collected a data set including 466 psoriasis patients and 520 healthy controls with 81 variables from only laboratory routine tests, such as age, total cholesterol, HDL cholesterol, blood pressure, albumin, and platelet distribution width. In this study, Boruta feature selection method was applied to select the most relevant features, with which a Random Forest model was constructed. The model was tested with 30 repetitions of 10-fold cross-validation. Our classification model yielded an average accuracy of 86.9%. 26 notable features were selected by Boruta, among which 15 features are confirmed from previous studies, and the rest are worth further investigations. The experimental results demonstrate that the machine learning approach has good potential in predictive modeling for the psoriasis disease given the information only from routine hospital tests.
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Changes of bone turnover markers after elderly hip fracture surgery.
Li, XP, Li, XY, Yang, MH, Zhu, SW, Wu, XB, Zhang, P
Journal of bone and mineral metabolism. 2021;(2):237-244
Abstract
INTRODUCTION Bone turnover markers (BTMs) can be used to monitor bone metabolism, while the actual clinical changing in hip fracture had not been certified to evaluate the changes of BTMs during the healing process after surgery of elderly hip fractures; and to get the effects of operation type, gender, serum 25(OH)D level, and age on bone turnover markers. MATERIALS AND METHODS A total of 100 elderly cases with hip fracture were selected, including 74 females and 26 males, and the patients were followed to 180-230 days after surgery. Serum levels of N-propeptide of type 1 collagen (P1NP), C-terminal crosslinking telopeptides of type 1 collagen (CTX), Osteocalcin (OC), and 25 hydroxy vitamin D (25OHD) were investigated. Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry (DXA). RESULTS (1) P1NP and CTX showed peak time at 30-60 days after operation, while OC keep going even at 180-230 days; P1NP showed less than 4 times elevation during healing, CTX and OC only had less than 2 times rise. (2) Female had higher serum CTX and OC than male, intramedullary nailing for intertrochanteric fracture patients had higher P1NP than hip replacement for femoral neck fracture patients, and both the degrees of increase were less than 50%. (3) Serum average 25(OH)D level had no effect on BTMs during the fracture healing; different from the young old (65-84 years), serum OC level of eldest older patients(≥ 85 years) decreased early in the process of fracture healing. CONCLUSIONS BTMs reached the peak level in 30-60 days after surgery, P1NP showed less than 4 times elevation, and CTX and OC had less than 2 times rise. It was not necessary to take gender into account when observing P1NP, and it was not necessary to take fracture and operation type into account when observing CTX and OC.
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Associations of D-Dimer on Admission and Clinical Features of COVID-19 Patients: A Systematic Review, Meta-Analysis, and Meta-Regression.
Zhao, R, Su, Z, Komissarov, AA, Liu, SL, Yi, G, Idell, S, Matthay, MA, Ji, HL
Frontiers in immunology. 2021;:691249
Abstract
BACKGROUND Dynamic D-dimer level is a key biomarker for the severity and mortality of COVID-19 (coronavirus disease 2019). How aberrant fibrinolysis influences the clinical progression of COVID-19 presents a clinicopathological dilemma challenging intensivists. METHODS We performed meta-analysis and meta regression to analyze the associations of plasma D-dimer with 106 clinical variables to identify a panoramic view of the derangements of fibrinolysis in 14,862 patients of 42 studies. There were no limitations of age, gender, race, and country. Raw data of each group were extracted separately by two investigators. Individual data of case series, median and interquartile range, and ranges of median or mean were converted to SDM (standard deviation of mean). FINDINGS The weighted mean difference of D-dimer was 0.97 µg/mL (95% CI 0.65, 1.29) between mild and severe groups, as shown by meta-analysis. Publication bias was significant. Meta-regression identified 58 of 106 clinical variables were associated with plasma D-dimer levels. Of these, 11 readouts were negatively related to the level of plasma D-dimer. Further, age and gender were confounding factors. There were 22 variables independently correlated with the D-dimer level, including respiratory rate, dyspnea plasma K+, glucose, SpO2, BUN (blood urea nitrogen), bilirubin, ALT (alanine aminotransferase), AST (aspartate aminotransferase), systolic blood pressure, and CK (creatine kinase). INTERPRETATION These findings support elevated D-dimer as an independent predictor for both mortality and complications. The identified D-dimer-associated clinical variables draw a landscape integrating the aggregate effects of systemically suppressive and pulmonary hyperactive derangements of fibrinolysis, and the D-dimer-associated clinical biomarkers, and conceptually parameters could be combined for risk stratification, potentially for tracking thrombolytic therapy or alternative interventions.
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Metabolomic Changes after Coffee Consumption: New Paths on the Block.
Favari, C, Righetti, L, Tassotti, M, Gethings, LA, Martini, D, Rosi, A, Antonini, M, Rubert, J, Manach, C, Dei Cas, A, et al
Molecular nutrition & food research. 2021;(3):e2000875
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Abstract
SCOPE Several studies suggest that regular coffee consumption may help preventing chronic diseases, but the impact of daily intake and the contribution of coffee metabolites in disease prevention are still unclear. The present study aims at evaluating whether and how different patterns of coffee intake (one cup of espresso coffee/day, three cups of espresso coffee/day, and one cup of espresso coffee/day and two cocoa-based products containing coffee two times per day) may impact endogenous molecular pathways. METHODS AND RESULTS A three-arm, randomized, crossover trial is performed in 21 healthy volunteers who consumed each treatment for one month. Urine samples are collected to perform untargeted metabolomics based on UHPLC-IMS-HRMS. A total of 153 discriminant metabolites are identified. Several molecular features are associated with coffee consumption, while others are linked with different metabolic pathways, such as phenylalanine, tyrosine, energy metabolism, steroid hormone biosynthesis, and arginine biosynthesis and metabolism. CONCLUSION This information has provided new insights into the metabolic routes by which coffee and coffee-related metabolites may exert effects on human health.