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The Turkish Journal of Pediatrics 2023Anemia is a common nutritional problem in children, especially those under five. Lactoferrin (Lf) as a supplement in treating iron deficiency anemia (IDA) has been... (Review)
Review
BACKGROUND
Anemia is a common nutritional problem in children, especially those under five. Lactoferrin (Lf) as a supplement in treating iron deficiency anemia (IDA) has been studied, but its results in children have not been reviewed. This review aims to evaluate the effect of lactoferrin on children with IDA.
METHODS
PubMed, ProQuest, EBSCO and Ovid databases were searched using a variation of keywords: lactoferrin, anemia, and children. The literature selected must be clinical trial-based in design. The years of the studies published were limited to 2012 and 2022.
RESULTS
Eleven studies were included in the final systematic review, consisting of 10 randomized controlled trials (RCTs) and 1 non-randomized trial. Serum ferritin (SF) and hemoglobin (Hb) were found to be increased in groups treated with Lf or a combination of Lf and elemental iron compared to iron only or placebo supplementation. Adverse events such as constipation, vomiting, anorexia, and abdominal pain were found; particularly, a significant decrease in constipation is seen in Lf-treated groups.
CONCLUSIONS
This study supports Lf as a superior treatment for IDA in children regarding the improvement in hematological and iron indices and fewer adverse effects.
Topics: Child; Humans; Abdominal Pain; Anemia, Iron-Deficiency; Constipation; Iron; Lactoferrin
PubMed: 37661669
DOI: 10.24953/turkjped.2022.670 -
Immunity, Inflammation and Disease Aug 2023Lactoferrin is a versatile protein with important modulatory functions in inflammation and immune response. This glycoprotein can bind and sequester iron and LPS,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lactoferrin is a versatile protein with important modulatory functions in inflammation and immune response. This glycoprotein can bind and sequester iron and LPS, thereby intervening in certain signaling pathways and biological processes. In the present meta-analysis, we aimed to pool experimental data regarding the immunomodulatory effects of lactoferrin and its derived peptides on the NF-κB signaling pathway.
MATERIALS
We searched PubMed, Google Scholar, and Web of Science databases and obtained all related articles published before April 2022. Finally, 25 eligible studies were selected, and their reports were analyzed.
METHODS
We used Review Manager Version 5.2 to compute the standardized mean difference (SMD) and its 95% confidence interval. In addition, the source of heterogeneity was explored using meta-regression and sensitivity analysis. The symmetry of the funnel plot and Egger's test were also used to evaluate publication bias utilizing Comprehensive Meta-Analysis Version 2.
RESULTS
Comparing the group of cells and animals exposed to lipopolysaccharide alone with the group that received pretreatment with lactoferrin and its derivatives, we observed significant reductions in TNF-α, IL-1 beta, and IL-6 levels by 8.73 pg/mL, 2.21 pg/mL, and 3.24 pg/mL, respectively, in the second group. Additionally, IKK-β, p-IκB, and NF-κB (p65) levels were significantly lower by 7.37-fold, 15.02-fold, and 3.88-fold, respectively, in various cells and tissues.
CONCLUSION
Based on the results of this meta-analysis, lactoferrin and its derived peptides can be considered potent prophylactic and therapeutic candidates against inflammation-associated diseases by targeting the NF-kB pathway.
Topics: Animals; NF-kappa B; Lactoferrin; Signal Transduction; Peptides; Inflammation; Lipopolysaccharides; Immunity
PubMed: 37647433
DOI: 10.1002/iid3.972 -
Clinical Chemistry and Laboratory... Feb 2024Dysregulation of hepcidin-iron axis is presumed to account for abnormal iron status in patients with chronic liver disease (CLD). Our aim is to determine the effect of... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Dysregulation of hepcidin-iron axis is presumed to account for abnormal iron status in patients with chronic liver disease (CLD). Our aim is to determine the effect of specific etiologies of CLD and of cirrhosis on serum hepcidin levels.
METHODS
PubMed, Embase, Web of Science were searched for studies comparing serum hepcidin levels in patients with CLD to that in controls using enzyme-linked immunosorbent assay. The study was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Guidelines. Statistical analysis was carried out with STATA using random effects model to calculate the mean difference (MD) between two groups.
RESULTS
Hepcidin levels were significantly lower in subjects with hepatitis C virus (16 studies) [MD -1.6 (95 % CI: -2.66 to -0.54), p<0.01] and alcoholic liver disease (3 studies) [MD -0.84 (95 % CI: -1.6 to -0.07), p=0.03] than controls. Serum hepcidin was significantly higher in subjects with non-alcoholic fatty liver disease (12 studies) [MD 0.62 (95 % CI: 0.21 to 1.03), p<0.01], but did not differ in subjects with hepatitis B and controls (eight studies) [MD -0.65 (95 % CI: -1.47 to 0.16), p=0.12]. Hepcidin levels were significantly lower in patients with cirrhosis of any etiology (four studies) [MD -1.02 (CI: -1.59 to -0.45), p<0.01] vs. controls (CI: confidence interval).
CONCLUSIONS
Serum hepcidin levels are altered in common forms of CLD albeit not in a consistent direction. Additional study is needed to determine how changes in hepcidin levels are related to dysregulation of iron metabolism in CLD.
Topics: Humans; Hepcidins; Ferritins; Liver Cirrhosis; Iron; Non-alcoholic Fatty Liver Disease
PubMed: 37540837
DOI: 10.1515/cclm-2023-0540 -
Renal Failure Dec 2023This meta-analysis aims to assess the efficacy and safety of roxadustat in treating anemia patients with dialysis-dependent (DD) chronic kidney disease (CKD). (Meta-Analysis)
Meta-Analysis
BACKGROUND
This meta-analysis aims to assess the efficacy and safety of roxadustat in treating anemia patients with dialysis-dependent (DD) chronic kidney disease (CKD).
METHODS
We comprehensively searched 5 databases for randomized controlled trials (RCTs) investigating roxadustat for anemia in DD-CKD patients. RevMan 5.0 was used to extract and synthesize data for meta-analysis.
RESULTS
Ten different RCTs (9 studies) and 5698 DD-CKD patients with anemia were included. Our findings revealed that when compared to the erythropoiesis-stimulating agents (ESAs) group, the roxadustat group showed increased hemoglobin levels [MD (Mean Difference) 0.25 g/dL (95%CI 0.14 g/dL to 0.36 g/dL), < 0.00001] and improved iron-utilization by increasing serum iron [MD 1.85 µmol/L], total iron binding capacity [MD 35.73 µg/dL], transferrin saturation [MD 1.19%], and transferrin level [MD 0.40 g/L]. In addition, we found that roxadustat significantly decreased the low-density lipoprotein-cholesterol [MD -0.39 mmol/L] and total cholesterol [MD -0.6 mmol/L]. In patients with a C-reactive protein level that exceeds the upper limit of the normal range, hemoglobin levels were higher for roxadustat than for ESAs [MD 0.39 g/dL]. Treatment-emergent adverse events, treatment-emergent serious adverse events, and major adverse cardiovascular events were not significantly different between the two groups.
CONCLUSIONS
The hemoglobin levels of DD-CKD patients were significantly increased and not affected by the inflammatory state after roxadustat treatment. Roxadustat also improved iron utilization, and it was not associated with higher treatment-emergent adverse events, treatment-emergent serious adverse events, and major adverse cardiovascular events when compared to ESAs.
Topics: Humans; Renal Dialysis; Anemia; Iron; Cholesterol, LDL; Glycine; Hematinics; Cardiovascular Diseases; Transferrins; Hemoglobins
PubMed: 37489561
DOI: 10.1080/0886022X.2023.2195011 -
Pediatric Neurology Aug 2023Wilson disease (WD) is a hereditary disorder of copper metabolism, caused by mutations in the ATP7B gene. There are more than 1000 pathogenic variants identified in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Wilson disease (WD) is a hereditary disorder of copper metabolism, caused by mutations in the ATP7B gene. There are more than 1000 pathogenic variants identified in ATP7B. R778L is the most common ATP7B mutation in China.
METHODS
To estimate whether R778L is associated with the onset age of WD and other clinical variables. Genotyping results of ATP7B gene were collected in our 22 patients with WD. We then conducted a systematic review and meta-analysis in databases, using the keywords Wilson disease and R778L mutation.
RESULTS
After the screening, a total of 23 studies were included, including 3007 patients with WD. Patients with R778L mutation presented at an earlier age (standardized mean difference [SMD] = -0.18 [95% confidence interval, -0.28 to 0.08], P = 0.0004) and had lower ceruloplasmin concentration (SMD = -0.21 [95% confidence interval, -0.40 to -0.02], P = 0.03) than the patients without the R778L mutation. However, sex (odds ratio [OR] = 1.07 [95% confidence interval, 0.89 to 1.29], P = 0.32) and first presentation were not associated with R778L mutation in WD (hepatic: OR = 1.37 [95% confidence interval, 0.87 to 2.16, P = 0.17; neurological: OR = 0.79 [95% confidence interval, 0.48 to 1.30, P = 0.35; mix: OR = 1.04 [95% confidence interval, 0.42 to 2.53, P = 0.87; asymptomatic/others: OR = 1.98 [95% confidence interval, 0.49 to 7.96, P = 0.34).
CONCLUSIONS
Our results indicated that the R778L mutation is associated with an earlier presentation and lower ceruloplasmin concentration in China.
Topics: Humans; Ceruloplasmin; China; Copper-Transporting ATPases; Hepatolenticular Degeneration; Mutation
PubMed: 37354629
DOI: 10.1016/j.pediatrneurol.2023.04.026 -
Seminars in Arthritis and Rheumatism Oct 2023To determine the prognostic factors of dermatomyositis with anti-melanoma differentiation-associated gene 5 (MDA5) antibody, a rare disease and often complicated by... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To determine the prognostic factors of dermatomyositis with anti-melanoma differentiation-associated gene 5 (MDA5) antibody, a rare disease and often complicated by life-threatening, rapidly progressive interstitial lung disease.
METHODS
Herein, we searched the Medline, Embase, and Cochrane Library databases and extracted studies published before August 23, 2022. Pooled analysis of hazard ratios (HRs) or odds ratios was used to identify prognostic factors for mortality among patients with anti-MDA5 antibody-positive dermatomyositis (MDA5+ DM).
RESULTS
Twenty-nine cohorts with 2,645 patients were included in this meta-analysis. Factors related to poor prognosis included old age (HR 1.54, 95% confidence interval (CI) 1.41-1.69, p < 0.01), male sex (HR 2.07, 95% CI 1.34-3.18, p < 0.01), rapidly progressive interstitial lung disease (RP-ILD) (HR 9.34, 95% CI 6.39-13.6, p < 0.01), high levels of ferritin (HR 1.05, 95% CI 1.01-1.08, p < 0.01), C-reactive protein (CRP) (HR 1.12, 95% CI 1.06-1.19, p < 0.01), creatine kinase (HR 1.05, 95% CI 1.03-1.07, p < 0.01), and lactate dehydrogenase (LDH) (HR 1.27, 95% CI 1.12-1.45, p < 0.01), whereas oxygen index (HR 0.990, 95% CI 0.988-0.992, p < 0.01), partial pressure of oxygen (HR 0.933, 95% CI 0.906-0.961, p < 0.01), forced vital capacity (HR 0.962, 95% CI 0.928-0.998, p = 0.038), and lymphocyte count (HR 0.421, 95% CI 0.282-0.629, p < 0.01) were associated with better outcomes.
CONCLUSIONS
Old age, male sex, hypoxemia, low forced vital capacity, lymphocytopenia, and high levels of ferritin, CRP, creatine kinase, and LDH are risk factors for mortality in patients with MDA5+ DM. However, a cautious interpretation of these results and further quality investigation are warranted.
Topics: Humans; Male; Autoantibodies; Dermatomyositis; Disease Progression; Ferritins; Interferon-Induced Helicase, IFIH1; Lung Diseases, Interstitial; Prognosis; Retrospective Studies; Risk Factors
PubMed: 37348186
DOI: 10.1016/j.semarthrit.2023.152231 -
Factors Influencing the Hepcidin Response to Exercise: An Individual Participant Data Meta-analysis.Sports Medicine (Auckland, N.Z.) Oct 2023Hepcidin, the master iron regulatory hormone, has been shown to peak 3-6 h postexercise, and is likely a major contributor to the prevalence of iron deficiency in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hepcidin, the master iron regulatory hormone, has been shown to peak 3-6 h postexercise, and is likely a major contributor to the prevalence of iron deficiency in athletes. Although multiple studies have investigated the hepcidin response to exercise, small sample sizes preclude the generalizability of current research findings.
OBJECTIVE
The aim of this individual participant data meta-analysis was to identify key factors influencing the hepcidin-exercise response.
METHODS
Following a systematic review of the literature, a one-stage meta-analysis with mixed-effects linear regression, using a stepwise approach to select the best-fit model, was employed.
RESULTS
We show that exercise is associated with a 1.5-2.5-fold increase in hepcidin concentrations, with pre-exercise hepcidin concentration accounting for ~ 44% of the variance in 3 h postexercise hepcidin concentration. Although collectively accounting for only a further ~ 3% of the variance, absolute 3 h postexercise hepcidin concentrations appear higher in males with lower cardiorespiratory fitness and higher pre-exercise ferritin levels. On the other hand, a greater magnitude of change between the pre- and 3 h postexercise hepcidin concentration was largely attributable to exercise duration (~ 44% variance) with a much smaller contribution from VOmax, pre-exercise ferritin, sex, and postexercise interleukin-6 (~ 6% combined). Although females tended to have a lower absolute 3 h postexercise hepcidin concentration [1.4 nmol·L, (95% CI [- 2.6, - 0.3]), p = 0.02] and 30% less change (95% CI [-54.4, - 5.1]), p = 0.02) than males, with different explanatory variables being significant between sexes, sample size discrepancies and individual study design biases preclude definitive conclusions.
CONCLUSION
Our analysis reveals the complex interplay of characteristics of both athlete and exercise session in the hepcidin response to exercise and highlights the need for further investigation into unaccounted-for mediating factors.
Topics: Male; Female; Humans; Hepcidins; Exercise; Iron; Ferritins; Athletes
PubMed: 37347443
DOI: 10.1007/s40279-023-01874-5 -
Reviews in Medical Virology Sep 2023Serum ferritin levels serves as biomarkers in many inflammatory and infectious diseases. This current systematic review and meta-analysis evaluated whether serum... (Meta-Analysis)
Meta-Analysis Review
Serum ferritin levels serves as biomarkers in many inflammatory and infectious diseases. This current systematic review and meta-analysis evaluated whether serum ferritin levels are associated with severe dengue and its utility as a biomarker of disease severity. Literature searches were conducted in PubMed, Scopus, ScienceDirect, the Cochrane library, and Google Scholar. A total of 18 studies examining the serum ferritin levels in dengue cases in the context of disease severity (nine studies having dengue classification as non-severe vs. severe dengue cases, and nine studies having dengue classification as dengue without warning signs (DwoWS), dengue with warning signs (DwWS), and severe dengue cases) were included and the quality of the studies was assessed using the Quality in Prognostic Factor Studies tool. The meta-analysis was performed using STATA software to calculate the effect size as a standardized mean difference (SMD) or Hedges 'g' for the continuous outcome. Higher serum ferritin levels were found in severe dengue cases compared to non-severe cases [SMD (Hedges 'g') 4.05 (95% C.I. 2.09-6.00), (I = 98.8%)]. In the second group, DwWS cases showed high serum ferritin levels compared to DwoWS [SMD 2.01 (95% C.I. 0.92-3.10), (I = 97.89%)], and severe dengue cases showed higher levels of serum ferritin compared to DwWS [SMD 2.66 (95% C.I. 1.72-4.48), (I = 98.78%)] and DwoWS cases [SMD 6.65 (95% C.I. 1.72-11.59), (I = 99.78%]. Subgroup analysis for the country of study (India vs. others), ferritin testing methods, and ferritin measurement day revealed testing method as a significant contributor to heterogeneity. To conclude, the present study suggests serum ferritin as a prognostic marker for dengue disease severity. Multi-centric studies involving a large number of dengue patients with a uniform case definition accounting for all the confounding variables might help in determining a universal cut-off value to discriminate between non-severe and severe dengue.
Topics: Humans; Severe Dengue; Prognosis; Biomarkers; Patient Acuity; Ferritins; Dengue
PubMed: 37347209
DOI: 10.1002/rmv.2468 -
Clinical Laboratory Jun 2023Several factors, including increased platelet aggregation, decreased platelet survival, decreased antithrombotic factors cause a hypercoagulable state in thalassemia... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several factors, including increased platelet aggregation, decreased platelet survival, decreased antithrombotic factors cause a hypercoagulable state in thalassemia patients. This is the first meta-analysis designed to summarize the association of age, splenectomy, gender, and serum ferritin and hemoglobin levels with the occurrence of asymptomatic brain lesions in thalassemia patients using MRI.
METHODS
This systematic review and meta-analysis was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist. We searched four major databases and included eight articles for this review. The quality of the included studies was assessed based on the Newcastle-Ottawa Scale checklist. Meta-analysis was performed using STATA 13. Odds ratio (OR) and standardized mean difference (SMD) were considered as effect sizes for comparing the categorical and continuous variables, respectively.
RESULTS
The pooled OR for splenectomy in patients with brain lesions compared to those without lesions was 2.25 (95% CI 1.22 - 4.17, p = 0.01). The pooled analysis for SMD of age between patients with/without brain lesions was statistically significant, 0.4 (95% CI 0.07 - 0.73, p = 0.017). The pooled OR for the occurrence of silent brain lesions was not statistically significant in males compared to females, 1.08 (95% CI 0.62 - 1.87, p = 0.784). The pooled SMD of Hb and serum ferritin in positive brain lesions compared to negatives were 0.01 (95% CI -0.28, 0.35, p = 0.939) and 0.03 (95% CI -0.28, 0.22, p = 0.817), respectively, which were not statistically significant.
CONCLUSIONS
Older age and splenectomy are risk factors for developing asymptomatic brain lesions in β-thalassemia patients. Physicians should consider a careful assessment of high-risk patients for starting prophylactic treatment.
Topics: Female; Male; Humans; beta-Thalassemia; Risk Factors; Odds Ratio; Ferritins; Brain
PubMed: 37307134
DOI: 10.7754/Clin.Lab.2022.221111 -
Clinical Laboratory Jun 2023Cardiac complications in patients with transfusion-dependent thalassemia (TDT) are one of the major causes of mortality in these patients which annually impose economic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cardiac complications in patients with transfusion-dependent thalassemia (TDT) are one of the major causes of mortality in these patients which annually impose economic burden on the endemic countries. Heart T2 MRI is a good modality for evaluating iron overload. Our aim was to investigate the pooled correlation between the serum ferritin level and heart iron overload in TDT patients and compare the effect size in different geographical areas.
METHODS
PRISMA checklist was used to summarize the literature search. Three major databases were used for the papers and exported into endnote for screening. Data were extracted into an Excel spreadsheet. The data were analyzed using STATA software. CC was considered as the effect size, and the amount of heterogeneity was indicated by I-squared. Meta-regression was used for age. Also, sensitivity analysis was performed.
RESULTS
The present study showed a statistically significant negative correlation of the serum ferritin level with heart T2 MRI: -0.30 (95% CI -0.34, -25). This correlation was not significantly affected by the patients' age (p-value: 0.874). Given different geographic area, most of the studies from different countries indicated that the correlation between the serum ferritin and heart T2 MRI was statistically significant.
CONCLUSIONS
The pooled analysis showed a significant negative moderate correlation between the serum ferritin level and heart T2 MRI in patients with TDT, regardless of their age. This issue underscores the importance of periodical evaluation of serum ferritin level in patients with TDT in developing countries with low financial supports and limited resources. Further studies are suggested to evaluate the pooled correlation of the serum ferritin level with iron concentration of other vital organs.
Topics: Humans; Magnetic Resonance Imaging; Thalassemia; Iron; Iron Overload; Ferritins
PubMed: 37307121
DOI: 10.7754/Clin.Lab.2022.220916