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1.
Relationship between erythrocyte phospholipid fatty acid composition and obesity in children and adolescents.
Tang, J, Yan, Y, Li, J, Yang, B, Zhao, X, Wan, Y, Zheng, JS, Mi, J, Li, D
Journal of clinical lipidology. 2019;(1):70-79.e1
Abstract
BACKGROUND Observational studies have reported inconsistent results on the association between circulating fatty acids and obesity. OBJECTIVE The objective of this study was to investigate the relationship between erythrocyte phospholipid fatty acid composition and obesity in children and adolescents. METHODS We conducted a case-control study including 1442 obese and 1442 normal-weight children and adolescents. Circulating fatty acid composition between cases and controls were compared both in the present study and literature-based meta-analysis. Individual fatty acids contributing most to discriminating cases and controls were identified by orthogonal partial least squares-discriminant analysis and their associations with obesity were explored by a conditional logistic regression model. RESULTS Five saturated fatty acids (14:0, 16:0, 17:0, 18:0, 20:0) were higher, 9 polyunsaturated fatty acids (18:3n-3, 20:3n-3, 20:5n-3, 22:5n-3, 22:6n-3, 18:2n-6, 20:2n-6, 20:3n-6, 20:4n-6) were lower in cases than in controls, while pooled results from the comparative meta-analysis were only consistent in 22:5n-3, 22:6n-3 and 18:2n-6. The orthogonal partial least squares-discriminant analysis model indicated that 16:0, 18:0, 20:4n-6, and 22:6n-3 were the fatty acids contributing most to discriminating cases and controls. In the conditional logistic regression model, significant positive associations were found for 16:0 (per 1 SD OR = 1.43, 95% CI, 1.35-1.52) and 18:0 (per 1 SD OR = 1.12, 95% CI, 1.09-1.16), while significant inverse associations were found for 20:4n-6 (per 1 SD OR = 0.63, 95% CI, 0.58-0.69) and 22:6n-3 (per 1 SD OR = 0.56, 95% CI, 0.52-0.61). CONCLUSIONS Erythrocyte phospholipid 16:0 and 18:0 were positively and 20:4n-6 and 22:6n-3 were inversely associated with obesity in children and adolescents.
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Drugs for preventing red blood cell dehydration in people with sickle cell disease.
Nagalla, S, Ballas, SK
The Cochrane database of systematic reviews. 2018;(10):CD003426
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Abstract
BACKGROUND Sickle cell disease is an inherited disorder of hemoglobin, resulting in abnormal red blood cells. These are rigid and may block blood vessels leading to acute painful crises and other complications. Recent research has focused on therapies to rehydrate the sickled cells by reducing the loss of water and ions from them. Little is known about the effectiveness and safety of such drugs. This is an updated version of a previously published review. OBJECTIVES To assess the relative risks and benefits of drugs to rehydrate sickled red blood cells. SEARCH METHODS We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register. We also searched online trials registries for any ongoing trials (01 July 2018).Last search of the Group's Haemoglobinopathies Trials Register: 08 October 2018. SELECTION CRITERIA Randomized or quasi-randomized controlled trials of drugs to rehydrate sickled red blood cells compared to placebo or an alternative treatment. DATA COLLECTION AND ANALYSIS Both authors independently selected studies for inclusion, assessed study quality and extracted data. MAIN RESULTS Of the 51 studies identified, three met the inclusion criteria, including 524 people with sickle cell disease aged between 12 and 65 years of age. One study tested the effectiveness of zinc sulphate as compared to placebo and the remaining two assessed senicapoc versus placebo. No deaths were seen in any of the studies (low-quality evidence). The zinc sulphate study showed a significant reduction in painful crises (in a total of 145 participants) over one and a half years, mean difference -2.83 (95% confidence interval -3.51 to -2.15) (moderate-quality evidence). However, analysis was restricted due to limited statistical data. Changes to red blood cell parameters and blood counts were inconsistent (very low-quality evidence). No serious adverse events were noted in the study. The Phase II dose-finding study of senicapoc (a Gardos channel blocker) compared to placebo showed that the high dose senicapoc showed significant improvement in change in hemoglobin level, the number and proportion of dense red blood cells, red blood cell count and indices and hematocrit value (very low-quality evidence). The results with low-dose senicapoc were similar to the high-dose senicapoc group but of lesser magnitude. There was no difference in the frequency of painful crises between the three groups (low-quality evidence). A subsequent Phase III study of senicapoc was terminated early since there was no difference observed between the treatment and control groups in the primary end point of painful crises. AUTHORS' CONCLUSIONS While the results of zinc for reducing sickle-related crises are encouraging, larger and longer-term multicenter studies are needed to evaluate the effectiveness of this therapy for people with sickle cell disease.While the Phase II and the prematurely terminated phase III studies of senicapoc showed that the drug improved red blood cell survival (depending on dose), this did not lead to fewer painful crises.Given this is no longer an active area of research, this review will no longer be regularly updated.
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Conversion ratios of n-3 fatty acids between plasma and erythrocytes: a systematic review and meta-regression.
Hu, XF, Sandhu, SK, Harris, WS, Chan, HM
The British journal of nutrition. 2017;(8):1162-1173
Abstract
As biomarkers of dietary intake or disease risk factor, n-3 fatty acid (FA) can be measured in plasma phospholipids (PL), total lipids (TL) or erythrocytes. However, the numeric relationships between n-3 FA in these lipid pools are not clear. Our goal was to derive conversion ratios for plasma and erythrocyte n-3 FA. Potential studies were identified through systematic literature search in PubMed, Embase and the Cochrane Library of Systematic reviews (1950 to October 2014). In all, fifty-six studies reporting n-3 in healthy individuals were included, of which thirty-four articles reported plasma PL and erythrocytes, and twenty-two reported plasma TL and erythrocytes. Meta-regressions were performed to quantify the ratio between plasma and erythrocyte n-3 FA weight percentages, controlling for covariates including age, sex and study design. The conversion ratios from plasma PL to erythrocytes for EPA, DHA, DPA and total n-3 PUFA are 0·75, 1·16, 2·32 and 1·22; the corresponding conversion ratios from plasma TL to erythrocytes are 1·00, 2·10, 3·85 and 2·08, respectively. The conversion ratios were validated using reported values from the literature and measured data from fifty individuals. The relative error of the predicted results were within 10 % of the mean reported values except for EPA, and the individual measured data except for DPA, in plasma TL. The conversion ratios between plasma PL and erythrocytes were more stable compared with plasma TL. Such conversion ratios will be useful for nutritionists or public health professionals to assess FA profiles of different populations using data collected with different methodologies.
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A systematic review and meta-analysis of the circulatory, erythrocellular and CSF selenium levels in Alzheimer's disease: A metal meta-analysis (AMMA study-I).
Reddy, VS, Bukke, S, Dutt, N, Rana, P, Pandey, AK
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2017;:68-75
Abstract
BACKGROUND Available studies in the literature on the selenium levels in Alzheimer's disease (AD) are inconsistent with some studies reporting its decrease in the circulation, while others reported an increase or no change as compared to controls. AIM: The objective of this study was to perform a meta-analysis of circulatory (plasma/serum and blood), erythrocyte and cerebrospinal fluid (CSF) selenium levels in AD compared controls. We also performed a meta-analysis of the correlation coefficients (r) to demonstrate the associations between selenium and glutathione peroxidase (GPx) in AD patients. METHODS All major databases were searched for eligible studies. We included 12 case-control/observational studies reporting selenium concentrations in AD and controls. Pooled-overall effect size as standardized mean difference (SMD) and pooled r-values were generated using Review Manager 5.3 and MedCalc 15.8 software. RESULTS Random-effects meta-analysis indicated a decrease in circulatory (SMD=-0.44), erythrocellular (SMD=-0.52) and CSF (SMD=-0.14) selenium levels in AD patients compared to controls. Stratified meta-analysis demonstrated that the selenium levels were decreased in both the subgroups with (SMD=-0.55) and without (SMD=-0.37) age matching between AD and controls. Our results also demonstrated a direct association between decreased selenium levels and GPx in AD. CONCLUSION This meta-analysis suggests that circulatory selenium concentration is significantly lower in AD patients compared to controls and this decrease in selenium is directly correlated with an important antioxidant enzyme, the GPx, in AD.
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Drugs for preventing red blood cell dehydration in people with sickle cell disease.
Nagalla, S, Ballas, SK
The Cochrane database of systematic reviews. 2016;:CD003426
Abstract
BACKGROUND Sickle cell disease is an inherited disorder of hemoglobin, resulting in abnormal red blood cells. These are rigid and may block blood vessels leading to acute painful crises and other complications. Recent research has focused on therapies to rehydrate the sickled cells by reducing the loss of water and ions from them. Little is known about the effectiveness and safety of such drugs. This is an updated version of a previously published review. OBJECTIVES To assess the relative risks and benefits of drugs to rehydrate sickled red blood cells. SEARCH METHODS We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.Last search of the Group's Trials Register: 28 November 2015. SELECTION CRITERIA Randomized or quasi-randomized controlled trials of drugs to rehydrate sickled red blood cells compared to placebo or an alternative treatment. DATA COLLECTION AND ANALYSIS Both authors independently selected studies for inclusion, assessed study quality and extracted data. MAIN RESULTS Of the 51 studies identified, three met the inclusion criteria. The first study tested the effectiveness of zinc sulphate to prevent sickle cell-related crises in a total of 145 participants and showed a significant reduction in painful crises over one and a half years, mean difference -2.83 (95% confidence interval -3.51 to -2.15). However, analysis was restricted due to limited statistical data. Changes to red cell parameters and blood counts were inconsistent. No serious adverse events were noted in the study.The second study was a Phase II dose-finding study of senicapoc (a Gardos channel blocker) compared to placebo. Compared to the placebo group the high dose senicapoc showed significant improvement in change in hemoglobin level, number and proportion of dense red blood cells, red blood cell count and indices and hematocrit. The results with low-dose senicapoc were similar to the high-dose senicapoc group but of lesser magnitude. There was no difference in the frequency of painful crises between the three groups. A subsequent Phase III study of senicapoc was terminated early since there was no difference observed between the treatment and control groups in the primary end point of painful crises. AUTHORS' CONCLUSIONS While the results of zinc for reducing sickle-related crises are encouraging, larger and longer-term multicenter studies are needed to evaluate the effectiveness of this therapy for people with sickle cell disease.While the Phase II and the prematurely terminated phase III studies of senicapoc showed that the drug improved red cell survival (depending on dose), this did not lead to fewer painful crises.We will continue to run searches to identify any potentially relevant trials; however, we do not plan to update other sections of the review until new trials are published.
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6.
Meta-analysis of erythrocyte polyunsaturated fatty acid biostatus in bipolar disorder.
McNamara, RK, Welge, JA
Bipolar disorders. 2016;(3):300-6
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Abstract
OBJECTIVES Dietary deficiency in polyunsaturated fatty acids (PUFAs), including the omega-3 fatty acids eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), and excesses in omega-6 fatty acids, including linoleic acid (LA; 18:2n-6) and arachidonic acid (AA; 20:4n-6), may be associated with the pathophysiology of bipolar disorder. In an effort to provide clarification regarding the relationship between PUFA biostatus and bipolar disorder, this meta-analysis investigated studies comparing erythrocyte (red blood cell) membrane PUFA composition in patients with bipolar disorder and healthy controls. METHODS A meta-analysis was performed on case-control studies comparing erythrocyte PUFA (EPA, DHA, LA and AA) levels in patients with bipolar I disorder and healthy controls. Standardized effect sizes were calculated and combined using a random effects model. RESULTS Six eligible case-control studies comprising n = 118 bipolar I patients and n = 147 healthy controls were included in the analysis. Compared with healthy controls, patients with bipolar I disorder exhibited robust erythrocyte DHA deficits (p = 0.0008) and there was a trend for lower EPA (p = 0.086). There were no significant differences in LA (p = 0.42) or AA (p = 0.64). CONCLUSIONS Bipolar I disorder is associated with robust erythrocyte DHA deficits. These findings add to a growing body of evidence implicating omega-3 PUFA deficiency in the pathophysiology of bipolar disorder.
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The impact of perioperative iron on the use of red blood cell transfusions in gastrointestinal surgery: a systematic review and meta-analysis.
Hallet, J, Hanif, A, Callum, J, Pronina, I, Wallace, D, Yohanathan, L, McLeod, R, Coburn, N
Transfusion medicine reviews. 2014;(4):205-11
Abstract
Perioperative anemia is common, yet detrimental, in surgical patients. However, red blood cell transfusions (RBCTs) used to treat anemia are associated with significant postoperative risks and worse oncologic outcomes. Perioperative iron has been suggested to mitigate perioperative anemia. This meta-analysis examined the impact of perioperative iron compared to no intervention on the need for RBCT in gastrointestinal surgery. We systematically searched Medline, Embase, Web of Science, Cochrane Central, and Scopus to identify relevant randomized controlled trials (RCTs) and nonrandomized studies (NRSs). We excluded studies investigating autologous RBCT or erythropoietin. Two independent reviewers selected the studies, extracted data, and assessed the risk of bias using the Cochrane tool and Newcastle-Ottawa scale. Primary outcomes were proportion of patients getting allogeneic RBCT and number of transfused patient. Secondary outcomes were hemoglobin change, 30-day postoperative morbidity and mortality, length of stay, and oncologic outcomes. A meta-analysis using random effects models was performed. The review was registered in PROSPERO (CRD42013004805). From 883 citations, we included 2 RCTs and 2 NRSs (n = 325 patients), all pertaining to colorectal cancer surgery. Randomized controlled trials were at high risk for bias and underpowered. One RCT and 1 NRS using preoperative oral iron reported a decreased proportion of patients needing RBCT. One RCT on preoperative intravenous iron and 1 NRS on postoperative PO iron did not observe a difference. Only 1 study revealed a difference in number of transfused patients. One RCT reported significantly increased postintervention hemoglobin. Among 3 studies reporting length of stay, none observed a difference. Other secondary outcomes were not reported. Meta-analysis revealed a trend toward fewer patients requiring RBCT with iron supplementation (risk ratio, 0.66 [0.42, 1.02]), but no benefit on the number of RBCT per patient (weighted mean difference, -0.91 [-1.61, -0.18]). Although preliminary evidence suggests that it may be a promising strategy, there is insufficient evidence to support the routine use of perioperative iron to decrease the need for RBCT in colorectal cancer surgery. Well-designed RCTs focusing on the need for RBCT and including long-term outcomes are warranted.
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Drugs for preventing red blood cell dehydration in people with sickle cell disease.
Nagalla, S, Ballas, SK
The Cochrane database of systematic reviews. 2012;(7):CD003426
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Abstract
BACKGROUND Sickle cell disease is an inherited disorder of hemoglobin, resulting in abnormal red blood cells. These are rigid and may block blood vessels leading to acute painful crises and other complications. Recent research has focused on therapies to rehydrate the sickled cells by reducing the loss of water and ions from them. Little is known about the effectiveness and safety of such drugs. OBJECTIVES To assess the relative risks and benefits of drugs to rehydrate sickled red blood cells. SEARCH METHODS We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.Last search of the Group's Trials Register: 25 October 2011. SELECTION CRITERIA Randomized or quasi-randomized controlled trials of drugs to rehydrate sickled red blood cells compared to placebo or an alternative treatment. DATA COLLECTION AND ANALYSIS Both authors independently selected studies for inclusion, assessed study quality and extracted data. MAIN RESULTS Of the 51 studies identified, three met the inclusion criteria. The first study tested the effectiveness of zinc sulphate to prevent sickle cell-related crises in a total of 145 participants and showed a significant reduction in painful crises over one and a half years, mean difference -2.83 (95% confidence interval -3.51 to -2.15). However, analysis was restricted due to limited statistical data. Changes to red cell parameters and blood counts were inconsistent. No serious adverse events were noted in the study.The second study was a Phase II dose-finding study of senicapoc (a Gardos channel blocker) compared to placebo. Compared to the placebo group the high dose senicapoc showed significant improvement in change in hemoglobin level, number and proportion of dense red blood cells, red blood cell count and indices and hematocrit. The results with low-dose senicapoc were similar to the high-dose senicapoc group but of lesser magnitude. There was no difference in the frequency of painful crises between the three groups. A subsequent Phase III study of senicapoc was terminated early since there was no difference observed between the treatment and control groups in the primary end point of painful crises. AUTHORS' CONCLUSIONS While the results of zinc for reducing sickle-related crises are encouraging, larger and longer-term multicenter studies are needed to evaluate the effectiveness of this therapy for people with sickle cell disease.While the Phase II and the prematurely terminated phase III studies of senicapoc showed that the drug improved red cell survival (depending on dose), this did not lead to fewer painful crises.
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Drugs for preventing red blood cell dehydration in people with sickle cell disease.
Nagalla, S, Ballas, SK
The Cochrane database of systematic reviews. 2010;(1):CD003426
Abstract
BACKGROUND Sickle cell disease is an inherited disorder of hemoglobin, resulting in abnormal red blood cells. These are rigid and may block blood vessels leading to acute painful crises and other complications. Recent research has focused on therapies to rehydrate the sickled cells by reducing the loss of water and ions from them. Little is known about the effectiveness and safety of such drugs. OBJECTIVES To assess the relative risks and benefits of drugs to rehydrate sickled red blood cells. SEARCH STRATEGY We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.Last search of the Group's Trials Register: 22 May 2009. SELECTION CRITERIA Randomized or quasi-randomized controlled trials of drugs to rehydrate sickled red blood cells compared to placebo or an alternative treatment. DATA COLLECTION AND ANALYSIS Both authors independently selected studies for inclusion, assessed study quality and extracted data. MAIN RESULTS Of the 47 studies identified, two met the inclusion criteria. The first study tested the effectiveness of zinc sulphate to prevent sickle cell-related crises in a total of 145 participants and showed a significant reduction in painful crises over one and a half years, mean difference -2.83 (95% confidence interval -3.51 to -2.15). However, analysis was restricted due to limited statistical data. Changes to red cell parameters and blood counts were inconsistent. No serious adverse events were noted in the study.The second study was a Phase II dose-finding study of senicapoc (Gardos channel blocker) compared to placebo. Compared to the placebo group the high dose senicapoc showed significant improvement in change in hemoglobin level, number and proportion of dense red blood cells, red blood cell count and indices and hematocrit. The results with low-dose senicapoc were similar to the high-dose senicapoc group but of lesser magnitude. There was no difference in the frequency of painful crises between the three groups. A subsequent Phase III study had to be stopped prematurely due to lack of reduction in the number of painful crisis. AUTHORS' CONCLUSIONS While the results of zinc for reducing sickle-related crises are encouraging, larger and longer-term multicentre studies are needed to evaluate the effectiveness of this therapy for people with sickle cell disease.Though the phase II study of senicapoc showed that the drug improved red cell survival, depending on dose, this did not lead to fewer painful crises; a subsequent phase III study was terminated prematurely for this reason.
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Red cell distribution width and mortality in older adults: a meta-analysis.
Patel, KV, Semba, RD, Ferrucci, L, Newman, AB, Fried, LP, Wallace, RB, Bandinelli, S, Phillips, CS, Yu, B, Connelly, S, et al
The journals of gerontology. Series A, Biological sciences and medical sciences. 2010;(3):258-65
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Abstract
BACKGROUND Red cell distribution width (RDW) is a quantitative measure of variability in the size of circulating erythrocytes with higher values reflecting greater heterogeneity in cell sizes. Recent studies have shown that higher RDW is associated with increased mortality risk in patients with clinically significant cardiovascular disease (CVD). Whether RDW is prognostic in more representative community-based populations is unclear. METHODS Seven relevant community-based studies of older adults with RDW measurement and mortality ascertainment were identified. Cox proportional hazards regression and meta-analysis on individual participant data were performed. RESULTS Median RDW values varied across studies from 13.2% to 14.6%. During 68,822 person-years of follow-up of 11,827 older adults with RDW measured, there was a graded increased risk of death associated with higher RDW values (p < .001). For every 1% increment in RDW, total mortality risk increased by 14% (adjusted hazard ratio [HR]: 1.14; 95% confidence interval [CI]: 1.11-1.17). In addition, RDW was strongly associated with deaths from CVD (adjusted HR: 1.15; 95% CI: 1.12-1.25), cancer (adjusted HR: 1.13; 95% CI: 1.07-1.20), and other causes (adjusted HR: 1.13; 95% CI: 1.07-1.18). Furthermore, the RDW-mortality association occurred in all major demographic, disease, and nutritional risk factor subgroups examined. Among the subset of 1,603 older adults without major age-associated diseases, RDW remained strongly associated with total mortality (adjusted HR: 1.32; 95% CI: 1.21-1.44). CONCLUSIONS RDW is a routinely reported test that is a powerful predictor of mortality in community-dwelling older adults with and without age-associated diseases. The biologic mechanisms underlying this association merit investigation.