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Signatures and Clinical Significance of Amino Acid Flux in Sarcopenia: A Systematic Review and Meta-Analysis.
Dai, M, Lin, T, Yue, J, Dai, L
Frontiers in endocrinology. 2021;:725518
Abstract
BACKGROUND Dysregulation of amino acids is closely linked to the initiation and progression of sarcopenia. We summarized recent advancements in the studies of amino acid profiles in sarcopenia and systematically presented the clinical significance of amino acid flux in sarcopenia. METHODS We systematically searched in MEDLINE, EMBASE, and Cochrane library from inception to June 1, 2021 to capture all studies examining metabolomics of sarcopenia. We used the following keywords: sarcopenia, metabonomics, metabolomics, amino acid profile, and mass spectrometry. Original articles comparing amino acid patterns between persons with and without sarcopenia were included. Two independent investigators independently completed title and abstract screening, data extraction, and quality evaluation. We used a random effects model to examine the association between amino acids levels and sarcopenia. Sensitivity analyses restricted the analyses to studies in which muscle mass was measured by bioelectrical impedance analysis. Study quality was evaluated according to the Agency for Healthcare Research and Quality (AHRQ) checklist. RESULTS The systematic research yielded six eligible articles, comprising 1,120 participants. Five studies used muscle mass in combination with physical performance and/or muscle strength as the criteria to diagnose sarcopenia, while one study used muscle mass as a diagnostic criterion alone. We found that the concentrations of branched-chain amino acids leucine (standardized mean difference [SMD] -1.249; 95% confidence interval [CI]: -2.275, -0.223, P = 0.02, I2 = 97.7%), isoleucine (SMD -1.077; 95% CI: -2.106, -0.049, P = 0.04, I2 = 97.8%), and aromatic amino acid tryptophan (SMD -0.923; 95% CI: -1.580, -0.265, P = 0.01, I2 = 89.9%) were significantly reduced in individuals with sarcopenia. Study results were robust in sensitivity analysis. CONCLUSIONS The homeostasis of amino acids is critical to maintaining muscle health. The profiles of amino acids might be useful biomarkers for the characterization of sarcopenia. Future studies are warranted to study the clinical significance of amino acids in the diagnosis and treatment of sarcopenia.
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Diagnostic value of radiolabeled amino acid PET for detection of pseudoprogression of brain tumor after treatment: a meta-analysis.
Kim, SJ, Ryul Shim, S
Nuclear medicine communications. 2019;(9):965-972
Abstract
PURPOSE The purpose of the current study was to investigate the diagnostic performance of radiolabeled amino acid PET for detection of pseudoprogression (PsP) of brain tumor after treatment through a systematic review and meta-analysis. METHODS The PubMed and EMBASE database, from the earliest available date of indexing through 15 February 2019, were searched for studies evaluating the diagnostic performance of radiolabeled amino acid PET for detection of PsP. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios, and constructed summary receiver operating characteristic (SROC) curves. RESULTS Across seven results from six studies (971 patients), the pooled sensitivity was 0.89 [95% confidence interval (CI): 0.82-0.94] without heterogeneity (I2 = 0.0) and a pooled specificity of 0.88 (95% CI: 0.76-0.94) without heterogeneity (I2=29.4). Likelihood ratio syntheses gave an overall positive likelihood ratio of 7.3 (95% CI: 3.6-14.7) and negative likelihood ratio of 0.12 (95% CI: 0.07-0.21). The pooled diagnostic odds ratio (DOR) was 60 (95% CI: 23-152). Hierarchical SROC curve indicates that the areas under the curve (AUC) was 0.92 (95% CI: 0.90-0.94). CONCLUSION The current meta-analysis showed the good sensitivity and specificity of radiolabeled amino acid PET for detection of PsP of brain tumor after treatment. Also, the DOR was high and SROC curve showed high AUC value.
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Safety and efficacy of Cerebrolysin in early post-stroke recovery: a meta-analysis of nine randomized clinical trials.
Bornstein, NM, Guekht, A, Vester, J, Heiss, WD, Gusev, E, Hömberg, V, Rahlfs, VW, Bajenaru, O, Popescu, BO, Muresanu, D
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2018;(4):629-640
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This meta-analysis combines the results of nine ischemic stroke trials, assessing efficacy of Cerebrolysin on global neurological improvement during early post-stroke period. Cerebrolysin is a parenterally administered neuropeptide preparation approved for treatment of stroke. All included studies had a prospective, randomized, double-blind, placebo-controlled design. The patients were treated with 30-50 ml Cerebrolysin once daily for 10-21 days, with treatment initiation within 72 h after onset of ischemic stroke. For five studies, original analysis data were available for meta-analysis (individual patient data analysis); for four studies, aggregate data were used. The combination by meta-analytic procedures was pre-planned and the methods of synthesis were pre-defined under blinded conditions. Search deadline for the present meta-analysis was December 31, 2016. The nonparametric Mann-Whitney (MW) effect size for National Institutes of Health Stroke Scale (NIHSS) on day 30 (or 21), combining the results of nine randomized, controlled trials by means of the robust Wei-Lachin pooling procedure (maximin-efficient robust test), indicated superiority of Cerebrolysin as compared with placebo (MW 0.60, P < 0.0001, N = 1879). The combined number needed to treat for clinically relevant changes in early NIHSS was 7.7 (95% CI 5.2 to 15.0). The additional full-scale ordinal analysis of modified Rankin Scale at day 90 in moderate to severe patients resulted in MW 0.61 with statistical significance in favor of Cerebrolysin (95% CI 0.52 to 0.69, P = 0.0118, N = 314). Safety aspects were comparable to placebo. Our meta-analysis confirms previous evidence that Cerebrolysin has a beneficial effect on early global neurological deficits in patients with acute ischemic stroke.
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Outcome of Carotid Artery Endarterectomy in Statin Users versus Statin-Naïve Patients: A Systematic Review and Meta-Analysis.
Texakalidis, P, Giannopoulos, S, Kokkinidis, DG, Jabbour, P, Reavey-Cantwell, J, Rangel-Castilla, L
World neurosurgery. 2018;:444-450.e1
Abstract
BACKGROUND Carotid artery endarterectomy (CEA) remains the most common surgical intervention for the treatment of symptomatic and asymptomatic carotid artery stenosis. Several studies have shown a lower risk of periprocedural adverse events in statin users who undergo coronary interventions or carotid artery stenting. The aim of this meta-analysis was to determine whether the use of statins is beneficial in patients undergoing CEA. METHODS This study was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies were identified through a search of PubMed, Scopus, and Cochrane until August 2017. A random effects model meta-analysis was conducted and the I2 statistic was used to assess for heterogeneity. RESULTS Six studies and 7053 patients overall were included. Thirty days after CEA, 157 (2.2%) patients had a stroke (1.4% in the statin-user group vs. 3% in the statin-naïve group). Despite the difference in the absolute rate of stroke, there was no statistically significant difference in the 30-day stroke rate (odds ratio [OR] 0.40; 95% confidence interval [CI] 0.15-1.09; I2 = 75.6%). Overall, 141 (2%) patients suffered 30-day myocardial infarction, with no significant difference between the 2 groups (OR 0.77; 95% CI 0.26-2.24; I2 = 77%). Patients who received statins before CEA were at a significantly lower risk for 30-day death (OR 0.26; 95% CI 0.10-0.61; I2 = 17.7%). CONCLUSIONS Statin users undergoing CEA were at a significantly lower risk for periprocedural death compared with statin-naïve patients. Despite an absolute difference in the stroke rate, the current meta-analysis did not detect a statistically significant difference in the 30-day stroke rate between statin-user and statin-naïve patients undergoing CEA.
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Abnormal circulating amino acid profiles in multiple metabolic disorders.
Okekunle, AP, Li, Y, Liu, L, Du, S, Wu, X, Chen, Y, Li, Y, Qi, J, Sun, C, Feng, R
Diabetes research and clinical practice. 2017;:45-58
Abstract
AIM: To evaluate circulating amino acids (AA) profiles in obesity, type 2 diabetes (T2D) and metabolic syndrome (MetS). METHODS Serum AA were profiled among 200; healthy, obese, T2D and MetS subjects matched by sex, age and BMI using ultra-high performance liquid chromatography tandem quadruple mass spectrometry (UPLC-TQ-MS). A meta-analysis, including 47 case-control studies (including the current study) on serum AA in obesity, T2D and MetS searched through October 2016 was conducted to explore the AA differences in obesity, T2D and MetS. RESULTS In comparison with healthy controls, 14 AA (10 increased and 4 decreased) were significantly altered (P<0.05) in all non-healthy subjects. Also, mean differences of valine (obese: 34.13 [27.70, 40.56]µmol/L, P<0.001, T2D: 19.49 [3.31, 35.68]µmol/L, P<0.05, MetS: 29.18 [16.04, 42.33]µmol/L, P<0.001), glutamic acid (obese: 18.62 [11.64, 25.61]µmol/L, P<0.001, T2D: 19.94 [0.28, 39.61]µmol/L, P<0.05, MetS: 12.45 [3.98, 20.91]µmol/L, P<0.001), proline (obese: 16.72 [6.20, 27.24]µmol/L, P<0.001, T2D: 20.72 [15.82, 25.61]µmol/L, P<0.001, MetS: 29.95 [25.18, 34.71]µmol/L, P<0.001) and isoleucine (obese: 11.39 [8.54, 14.24]µmol/L, P<0.001, T2D: 7.37 [1.52, 13.22]µmol/L, P<0.05, MetS: 10.40 [4.90, 15.89]µmol/L, P<0.001) were significantly higher compared to healthy controls. Similarly, mean differences of glycine (obese: -30.99 [-39.69, -22.29]µmol/L, P<0.001, T2D: -30.37 [-41.80, -18.94]µmol/L, P<0.001 and MetS: -35.24 [-39.28, -31.21]µmol/L, P<0.001) were significantly lower compared to healthy controls. CONCLUSION In both the case-control study and meta-analysis, obesity was related to the most circulating AA changes, followed by MetS and T2D. Valine, isoleucine, glutamic acid and proline increased, while Glycine decreased in all metabolic disorders.
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Intravenous nutrients for preventing inadvertent perioperative hypothermia in adults.
Warttig, S, Alderson, P, Lewis, SR, Smith, AF
The Cochrane database of systematic reviews. 2016;(11):CD009906
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BACKGROUND Inadvertent perioperative hypothermia (a drop in core temperature to below 36°C) occurs because normal temperature regulation is disrupted during surgery, mainly because of the effects of anaesthetic drugs and exposure of the skin for prolonged periods. Many different ways of maintaining body temperature have been proposed, one of which involves administration of intravenous nutrients during the perioperative period that may reduce heat loss by increasing metabolism, thereby increasing heat production. OBJECTIVES To assess the effectiveness of preoperative or intraoperative intravenous nutrients in preventing perioperative hypothermia and its complications during surgery in adults. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL; November 2015) in the Cochrane Library; MEDLINE, Ovid SP (1956 to November 2015); Embase, Ovid SP (1982 to November 2015); the Institute for Scientific Information (ISI) Web of Science (1950 to November 2015); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL, EBSCO host; 1980 to November 2015), as well as the reference lists of identified articles. We also searched the Current Controlled Trials website and ClincalTrials.gov. SELECTION CRITERIA Randomized controlled trials (RCTs) of intravenous nutrients compared with control or other interventions given to maintain normothermia in adults undergoing surgery. DATA COLLECTION AND ANALYSIS Two review authors extracted data and assessed risk of bias for each included trial, and a third review author checked details if necessary. We contacted some study authors to request additional information. MAIN RESULTS We included 14 trials (n = 565), 13 (n = 525) of which compared intravenous administration of amino acids to a control (usually saline solution or Ringer's lactate). The remaining trial (n = 40) compared intravenous administration of fructose versus a control. We noted much variation in these trials, which used different types of surgery, variable durations of surgery, and different types of participants. Most trials were at high or unclear risk of bias owing to inappropriate or unclear randomization methods, and to unclear participant and assessor blinding. This may have influenced results, but it is unclear how results might have been influenced.No trials reported any of our prespecified primary outcomes, which were risk of hypothermia and major cardiovascular events. Therefore, we decided to analyse data related to core body temperature instead as a primary outcome. It was not possible to conduct meta-analysis of data related to amino acid infusion for the 60-minute and 120-minute time points, as we observed significant statistical heterogeneity in the results. Some trials showed that higher temperatures were associated with amino acids, but not all trials reported statistically significant results, and some trials reported the opposite result, where the amino acid group had a lower core temperature than the control group. It was possible to conduct meta-analysis for six studies (n = 249) that provided data relating to the end of surgery. Amino acids led to a statistically significant increase in core temperature in comparison to those receiving control (MD = 0.46°C 95% CI 0.33 to 0.59; I2 0.0%; random-effects; moderate quality evidence).Three trials (n = 155) reported shivering as an outcome. Meta-analysis did not show a clear effect, and so it is uncertain whether amino acids reduce the risk of shivering (RR 0.36, 95% CI 0.13 to 1.00; I2 = 93%; random-effects model; very low-quality evidence). AUTHORS' CONCLUSIONS Intravenous amino acids may keep participants up to a half-degree C warmer than the control. This difference was statistically significant at the end of surgery, but not at other time points. However, the clinical importance of this finding remains unclear. It is also unclear whether amino acids have any effect on the risk of shivering and if intravenous nutrients confer any other benefits or harms, as high-quality data about these outcomes are lacking.
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Metabolic profiling of alcohol consumption in 9778 young adults.
Würtz, P, Cook, S, Wang, Q, Tiainen, M, Tynkkynen, T, Kangas, AJ, Soininen, P, Laitinen, J, Viikari, J, Kähönen, M, et al
International journal of epidemiology. 2016;(5):1493-1506
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BACKGROUND High alcohol consumption is a major cause of morbidity, yet alcohol is associated with both favourable and adverse effects on cardiometabolic risk markers. We aimed to characterize the associations of usual alcohol consumption with a comprehensive systemic metabolite profile in young adults. METHODS Cross-sectional associations of alcohol intake with 86 metabolic measures were assessed for 9778 individuals from three population-based cohorts from Finland (age 24-45 years, 52% women). Metabolic changes associated with change in alcohol intake during 6-year follow-up were further examined for 1466 individuals. Alcohol intake was assessed by questionnaires. Circulating lipids, fatty acids and metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays. RESULTS Increased alcohol intake was associated with cardiometabolic risk markers across multiple metabolic pathways, including higher lipid concentrations in HDL subclasses and smaller LDL particle size, increased proportions of monounsaturated fatty acids and decreased proportion of omega-6 fatty acids, lower concentrations of glutamine and citrate (P < 0.001 for 56 metabolic measures). Many metabolic biomarkers displayed U-shaped associations with alcohol consumption. Results were coherent for men and women, consistent across the three cohorts and similar if adjusting for body mass index, smoking and physical activity. The metabolic changes accompanying change in alcohol intake during follow-up resembled the cross-sectional association pattern (R2 = 0.83, slope = 0.72 ± 0.04). CONCLUSIONS Alcohol consumption is associated with a complex metabolic signature, including aberrations in multiple biomarkers for elevated cardiometabolic risk. The metabolic signature tracks with long-term changes in alcohol consumption. These results elucidate the double-edged effects of alcohol on cardiovascular risk.
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Statin use prior to angiography for the prevention of contrast-induced acute kidney injury: a meta-analysis of 19 randomised trials.
Thompson, K, Razi, R, Lee, MS, Shen, A, Stone, GW, Hiremath, S, Mehran, R, Brar, SS
EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. 2016;(3):366-74
Abstract
AIMS: A systematic review and a meta-analysis were performed to define better the role of statin use prior to angiography in preventing contrast-induced acute kidney injury (CI-AKI). METHODS AND RESULTS MEDLINE, Embase, Cochrane Library, references from review articles, and conference proceedings were searched, with no language restriction, for randomised controlled trials (RCT) evaluating the use of statin therapy prior to angiography for the prevention of CI-AKI. Nineteen RCTs including 7,161 patients were identified. The pooled analysis demonstrated a significant reduction in the incidence of CI-AKI in patients treated with statin prior to invasive angiography when compared with control (RR 0.52; 95% CI: 0.40-0.67). Patients with chronic kidney disease stage 3 or worse were largely underrepresented in these trials, and statin therapy did not significantly reduce the risk of CI-AKI in the three studies which enrolled a patient population with a mean eGFR of <60 ml/min (RR 0.54; 95% CI: 0.2-1.42). CONCLUSIONS This meta-analysis suggests a potential benefit for statin use prior to angiography to reduce the incidence of CI-AKI. Additional research is needed to define better the benefits of statin therapy prior to angiography to prevent CI-AKI, especially in high-risk patients with chronic kidney disease who were largely underrepresented in the available trials.
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Association of Plasma Small-Molecule Intermediate Metabolites With Age and Body Mass Index Across Six Diverse Study Populations.
Kraus, WE, Pieper, CF, Huffman, KM, Thompson, DK, Kraus, VB, Morey, MC, Cohen, HJ, Ravussin, E, Redman, LM, Bain, JR, et al
The journals of gerontology. Series A, Biological sciences and medical sciences. 2016;(11):1507-1513
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BACKGROUND Older age and obesity are associated with metabolic dysregulation; the mechanism by which these factors impact metabolism across the lifespan is important, but relatively unknown. We evaluated a panel of amino acids (AAs) and acylcarnitines (ACs) to identify effects of age and adiposity (body mass index) on circulating small-molecule metabolites in a meta-analysis of six diverse study populations. METHODS Targeted metabolic profiling was performed in six independent studies, representing 739 subjects with a broad range of age, body mass index, health states, and ethnic origin. Principal components analysis was performed on log-normalized values for AAs and ACs separately, generating one AC factor and two AA factors for each study. A common AC factor consisted primarily of acetylcarnitine, medium-chain AC, and several long-chain AC. AA Factor 1 consisted primarily of large neutral AAs. Glycine was its own factor. RESULTS Metabolic profiling and factor analysis identified clusters of related metabolites of lipid and AA metabolism that were consistently associated with age and body mass in a series of studies with a broad range of age, body mass index, and health status. An inverse association of glycine with body mass index and male gender supports its role as a marker of favorable metabolic health. CONCLUSIONS An important focus of future investigations should be to determine whether these clusters of metabolic intermediates are possible early predictors of health outcomes associated with body mass; are involved with accelerated aging; are involved in the causative pathway of aging; and how modification of these metabolic pathways impact the biology of aging.
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Metabolic signatures of birthweight in 18 288 adolescents and adults.
Würtz, P, Wang, Q, Niironen, M, Tynkkynen, T, Tiainen, M, Drenos, F, Kangas, AJ, Soininen, P, Skilton, MR, Heikkilä, K, et al
International journal of epidemiology. 2016;(5):1539-1550
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BACKGROUND Lower birthweight is associated with increased susceptibility to cardiometabolic diseases in adulthood, but the underlying molecular pathways are incompletely understood. We examined associations of birthweight with a comprehensive metabolic profile measured in adolescents and adults. METHODS High-throughput nuclear magnetic resonance metabolomics and biochemical assays were used to quantify 87 circulating metabolic measures in seven cohorts from Finland and the UK, comprising altogether 18 288 individuals (mean age 26 years, range 15-75). Metabolic associations with birthweight were assessed by linear regression models adjusted for sex, gestational age and age at blood sampling. The metabolic associations with birthweight were compared with the corresponding associations with adult body mass index (BMI). RESULTS Lower birthweight adjusted for gestational age was adversely associated with cardiometabolic biomarkers, including lipoprotein subclasses, fatty acids, amino acids and markers of inflammation and impaired liver function (P < 0.0015 for 46 measures). Associations were consistent across cohorts with different ages at metabolic profiling, but the magnitudes were weak. The pattern of metabolic deviations associated with lower birthweight resembled the metabolic signature of higher adult BMI (R2 = 0.77) assessed at the same time as the metabolic profiling. The resemblance indicated that 1 kg lower birthweight is associated with similar metabolic aberrations as caused by 0.92 units higher BMI in adulthood. CONCLUSIONS Lower birthweight adjusted for gestational age is associated with adverse biomarker aberrations across multiple metabolic pathways. Coherent metabolic signatures between lower birthweight and higher adult adiposity suggest that shared molecular pathways may potentially underpin the metabolic deviations. However, the magnitudes of metabolic associations with birthweight are modest in comparison to the effects of adiposity, implying that birthweight is only a weak indicator of the metabolic risk profile in adulthood.