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Reviews in Medical Virology Jan 2022It has been demonstrated that lactoferrin (LF) plays a role in host defence, but evidence on its potential antiviral property from clinical studies is fragmented. Our... (Review)
Review
It has been demonstrated that lactoferrin (LF) plays a role in host defence, but evidence on its potential antiviral property from clinical studies is fragmented. Our systematic review aimed at identifying the effects of orally administered LF against virus infections. The systematic search was conducted on PubMed, Scopus, Web of Science, BioRxiv.org and ClinicalTrials.gov from database inception to 7th January 2021. Eligible articles investigated any virus family and provided data on the effects of orally administered LF of any origin in the prevention and/or management of confirmed viral infections in people of any age. A narrative synthesis of the results was performed. Quality was assessed with the Cochrane Risk-Of-Bias and ROBINS-1 tools. A total of 27 records were included, nine of which were registered protocols. We found data on Flaviviridae (n = 10), Retroviridae (n = 3), Coronaviridae (n = 2), Reoviridae (n = 2) and Caliciviridae (n = 1). Most published trials were at high risk of bias. The findings were heterogeneous across and within viral families regarding virological, immunological and biological response, with no clear conclusion. Some weak but positive results were reported about decrease of symptom severity and duration, or reduction in viral loads. Despite high tolerability, the effects of LF as oral supplement are still inconsistent, both in preventing and managing viral infections. Small sample sizes, variety in recruitment and treatment protocols, and low study quality may have contributed to such heterogeneity. Better-designed studies are needed to further investigate its potential benefits against viral infections, including SARS-CoV-2.
Topics: Anti-Infective Agents; COVID-19; Humans; Lactoferrin; SARS-CoV-2; Virus Diseases
PubMed: 34133812
DOI: 10.1002/rmv.2261 -
Transfusion Clinique Et Biologique :... Feb 2023Iron overload is a common complication experienced by transfusion-dependent children with hemoglobin disorders. Chelators such as deferasirox (DFX) and deferiprone (DFP)... (Meta-Analysis)
Meta-Analysis
No difference in myocardial iron concentration and serum ferritin with deferasirox and deferiprone in pediatric patients with hemoglobinopathies: A systematic review and meta-analysis.
OBJECTIVES
Iron overload is a common complication experienced by transfusion-dependent children with hemoglobin disorders. Chelators such as deferasirox (DFX) and deferiprone (DFP) are effective in overcoming this problem. We conducted this systematic review and meta-analysis to evaluate the effectiveness of DFX compared to DFP in treating iron overload amongst pediatric patients with hemoglobin disorders.
MATERIAL AND METHODS
PubMed and Cochrane Central were searched from their inception until Dec 21 2021, for randomized clinical trials (RCTs) and observational studies, which assessed the efficacy of DFX compared to DFP in the treatment of inherited hemoglobin disorders. The outcomes of interest included myocardial iron concentration (MRI T2*) at the end of the trial and change in mean serum ferritin (SF) levels at the 6 and 12 months mark. Weighted mean differences (WMDs) with their corresponding 95% confidence intervals (CIs) were calculated for continuous outcomes using random effects model.
RESULTS
A total of 5 studies comprising 607 children were included. The results of our analysis revealed no significant difference between DFX and DFP in MRI T2* at the end of treatment (WMD: -0.92; 95% CI [-3.35, 1.52]; p = 0.46; I = 0). Moreover, there has been no significant difference noted in SF levels at both 6 months (WMD: 97.31; 95% CI [-236.16, 430.77]; p = 0.57; I = 0) and 12 months (WMD: 46.99; 95% CI [-191.42, 285.40]; p = 0.70; I = 0) respectively.
CONCLUSION
Our analysis shows no significant difference between the efficacy of DFX and DFP in the management of iron overload in children with inherited blood disorders. Future large-scale clinical trials are required to further validate our results.
Topics: Humans; Child; Iron; Deferasirox; Deferiprone; Iron Chelating Agents; Benzoates; Triazoles; Pyridones; Iron Overload; beta-Thalassemia; Hemoglobinopathies; Ferritins
PubMed: 35878782
DOI: 10.1016/j.tracli.2022.07.004 -
Journal of Medical Genetics Apr 2020Pheochromocytoma and paraganglioma (PPGL) are tumours that arise from chromaffin cells. Some genetic mutations influence PPGL, among which, those in genes encoding... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pheochromocytoma and paraganglioma (PPGL) are tumours that arise from chromaffin cells. Some genetic mutations influence PPGL, among which, those in genes encoding subunits of succinate dehydrogenase (SDHA, SDHB, SDHC and SDHD) and assembly factor (SDHAF2) are the most relevant. However, the risk of metastasis posed by these mutations is not reported except for SDHB and SDHD mutations. This study aimed to update the metastatic risks, considering prevalence and incidence of each SDHx mutation, which were dealt formerly all together.
METHODS
We searched EMBASE and MEDLINE and selected 27 articles. The patients included in the studies were divided into three groups depending on the presence of PPGL. We checked the heterogeneity between studies and performed a meta-analysis using Hartung-Knapp-Sidik-Jonkman method based on a random effect model.
RESULTS
The highest PPGL prevalence was for SDHB mutation, ranging from 23% to 31%, and for SDHC mutation (23%), followed by that for SDHA mutation (16%). The lowest prevalence was for SDHD mutation, ranging from 6% to 8%. SDHAF2 mutation showed no metastatic events. The PPGL incidence showed a tendency similar to that of its prevalence with the highest risk of metastasis posed by SDHB mutation (12%-41%) and the lowest risk by SDHD mutation (~4%).
CONCLUSION
There was no integrated evidence of how SDHx mutations are related to metastatic PPGL. However, these findings suggest that SDHA, SDHB and SDHC mutations are highly associated and should be tested as indicators of metastasis in patients with PPGL.
Topics: Adrenal Gland Neoplasms; Electron Transport Complex II; Germ-Line Mutation; Heterozygote; Humans; Membrane Proteins; Mitochondrial Proteins; Neoplasm Metastasis; Paraganglioma; Pheochromocytoma; Succinate Dehydrogenase
PubMed: 31649053
DOI: 10.1136/jmedgenet-2019-106324 -
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 -
The Lancet. Haematology Jul 2024Iron deficiency is a highly prevalent condition, which contributes to unnecessary morbidity, mortality, and health inequity. A serum ferritin concentration of less than...
Iron deficiency is a highly prevalent condition, which contributes to unnecessary morbidity, mortality, and health inequity. A serum ferritin concentration of less than 30 μg/L has a high specificity and sensitivity for diagnosing iron deficiency in adults, but the laboratory reported lower limit of normal (LLN) is typically lower. These LLNs might not be rooted in rigorous scientific evidence and might be contributing to structural underdiagnosis of iron deficiency. A systematic review was done per systematic reviews and meta-analysis guidelines with the use of medical literature databases from inception of each database to Nov 30, 2021, to identify studies that determined ferritin reference intervals in healthy adults and grey literature search for the five most common ferritin assays (registration number CRD42022268844). The objectives were to systematically summarise the ferritin reference intervals and to do a methodological quality assessment of the included studies. 2306 studies were screened and 61 full texts were included. 37 studies were eligible for analysis of the ferritin LLN in the general population. The population the sample was comprised of was a total of 21 882 females and 23 650 males participants. The ferritin LLN was a median of 8 μg/L (IQR 5-15) and mean of 9 μg/L (SD 11) in females and a median of 25 μg/L (IQR 16-44) and mean of 25 μg/L (SD 29) in males. 30 (49%) of 61 studies did not explicitly screen for patients at risk of iron deficiency, and 32 (52%) did not refer to a reference interval establishment guideline (eg, guideline recommended by Clinical and Laboratory Standards Institute). The five most used commercial ferritin laboratory assays reported reference intervals with a median LLN of 11 (IQR 9-12) and mean of 9 μg/L (SD 4) for females and median of 22 (IQR 22-24) and mean of 23 μg/L (SD 4) for males. In the literature, serum ferritin reference intervals in healthy adults consistently report a LLN of less than 30 μg/L. Data driving these ferritin reference intervals are at high risk of bias, given no exclusion of individuals at risk for iron deficiency in the presumed normal population sample and no adherence to reference interval establishment standards. We suggest the use of evidence-based laboratory clinical decision limits to diagnose iron deficiency.
Topics: Adult; Female; Humans; Male; Anemia, Iron-Deficiency; Ferritins; Reference Values
PubMed: 38937026
DOI: 10.1016/S2352-3026(24)00103-0 -
Medicine Nov 2020It has been reported that polymorphisms of transferrin (TF) G258A and transferrin receptor (TFR) A82G might be associated with susceptibility to Parkinson disease (PD). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It has been reported that polymorphisms of transferrin (TF) G258A and transferrin receptor (TFR) A82G might be associated with susceptibility to Parkinson disease (PD).
OBJECTIVE
Owing to limitation of sample size and inconclusive results, we conducted a meta-analysis to clarify the association.
METHODS
By searching PubMed, Embase, Chinese National Knowledge Infrastructure, China Biological Medicine Database, and Wanfang Databases, the published articles about studies of the association of the TF G258A, TFR A82G gene polymorphisms with the risk of PD were collected. Q-statistics and I statistics were calculated to examine heterogeneity and summary odds ratios (ORs) and 95% confidence intervals (95%CI) were evaluated the association.
RESULTS
Five studies assessed the relationship between TF G258A and risk of PD. A significant increased protective of A allele and AA genotype was observed in allele model and recessive model (the allele model A vs G: OR = 0.54, 95%CI 0.40-0.72, P < .001; the recessive model AA vs GA + GG: OR = 0.32, 95%CI 0.20-0.52, P < .001). The remaining models of the TF G258A genotype showed no significant association with PD risk, while the protective tendency were increased (the heterozygote model GA vs GG: OR = 0.93, 95%CI 0.61-1.43, P = .75; the homozygous model AA vs GG: OR = 0.47, 95%CI 0.21-1.04, P = .06; the dominant model GA + AA vs GG: OR = 0.75, 95%CI 0.50-1.11, P = .15). There was also a lack of association between TFR A82G polymorphism and PD (the allele model G vs A: OR = 0.92, 95%CI 0.75-1.13, P = .43; the heterozygote model AG vs AA: OR = 1.17, 95%CI 0.79-1.71, P = .43; the homozygous model GG vs AA: OR = 0.91, 95%CI 0.60-139, P = .66; the dominant model AG + GG vs AA: OR = 1.05, 95%CI 0.73-1.49, P = .81; the recessive model GG vs AG +AA: OR = 0.80, 95%CI 0.59-1.09, P = .16).
CONCLUSION
Our study suggests that TF G258A polymorphism may be associated with PD, while TFR A82G polymorphism may not contribute to PD based on the current evidence.
Topics: Alleles; Genetic Predisposition to Disease; Genotype; Humans; Models, Genetic; Parkinson Disease; Polymorphism, Single Nucleotide; Receptors, Transferrin; Transferrin
PubMed: 33235126
DOI: 10.1097/MD.0000000000023432 -
Frontiers in Public Health 2022Hepcidin has been identified as a systemic iron-regulatory hormone. Recent studies have suggested that iron metabolism disorders may be involved in the pathogenesis of... (Meta-Analysis)
Meta-Analysis
BACKGROUNDS
Hepcidin has been identified as a systemic iron-regulatory hormone. Recent studies have suggested that iron metabolism disorders may be involved in the pathogenesis of acute respiratory distress syndrome and multiple organ dysfunction in coronavirus disease 2019 (COVID-19).
OBJECTIVES
To re-evaluate the hepcidin-related iron metabolism parameters and explore the relationship between hepcidin-mediated iron dysmetabolism and COVID-19 severity.
METHODS
COVID-19 is classified as mild and moderate as non-severe, severe and critical as severe. A meta-analysis was conducted. Four bibliographic databases were comprehensively searched up to December 31st 2021.
RESULTS
Six unique studies with data from 477 COVID-19 patients were included. Compared to non-severe cases, severe cases had higher hepcidin (standardized mean difference (SMD), -0.39; 95% Confidence Interval (CI) [-0.76, -0.03]; = 0.03) and ferritin (SMD, -0.84; 95% CI [-1.30, -0.38]; = 0.0004). In five out of six studies, a total of 427 patients were tested for serum iron, and there were significant differences in their levels between severe and non-severe cases (SMD, 0.22; 95% CI [0.02, 0.41]; = 0.03). A total of 320 patients from four out of six studies were tested for transferrin saturation, and the statistical difference was not significant (SMD, 0.06; 95% CI [-0.17, 0.28]; = 0.64).
CONCLUSION
Severe COVID-19 cases had higher serum levels of hepcidin and ferritin, and lower serum iron, without significant differences in transferrin saturation. Further studies are needed to verify whether targeting the hepcidin-mediated iron metabolism axis may influence the outcome and treatment of COVID-19.
Topics: COVID-19; Ferritins; Hepcidins; Humans; Iron; Transferrin
PubMed: 35558525
DOI: 10.3389/fpubh.2022.881412 -
Biomedical and Environmental Sciences :... Aug 2021This study aims to assess the dose-response relationship between serum ferritin (SF) and metabolic syndrome (MetS) in the two sexes. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aims to assess the dose-response relationship between serum ferritin (SF) and metabolic syndrome (MetS) in the two sexes.
METHODS
We searched for articles on PubMed, the Cochrane Library, EMBASE, and the Web of Science databases that were published from 1950 to 2020. The summary odds ratio ( ) and 95% confidence interval ( ) of the association between SF and MetS were estimated using a random-effects model through a meta-analysis. Based on the methods described by Greenland and Longnecker, we explored the dose-response relationship between the two sexes.
RESULTS
This study included 14 studies and 74,710 samples. The results of the classical meta-analysis showed that SF was positively associated with MetS ( = 1.77, 95% : 1.59-1.98). Regarding the components of MetS (8 studies included), the results showed that SF was positively associated with abdominal obesity ( = 1.42, 95% : 1.24-1.62), elevated fasting plasma glucose ( = 1.84, 95% : 1.50-2.25), elevated blood pressure ( = 1.17, 95% : 1.08-1.26), elevated triglycerides ( = 2.09, 95% : 1.72-2.54), and reduced high-density lipoprotein cholesterol ( = 1.33, 95% : 1.19-1.49). In the linear dose-response meta-analysis, the s of males, females, and postmenopausal females were 1.14 (95% : 1.13-1.16), 1.32 (95% : 1.26-1.39), and 1.34 (95% : 1.22-1.47), respectively.
CONCLUSIONS
Our study shows that SF is significantly and positively associated with MetS, and the risk in the male population is higher than that in the female population. This finding also supports the recommendation of using SF as an early warning marker of MetS.
Topics: Biomarkers; Female; Ferritins; Humans; Male; Metabolic Syndrome; Risk Factors; Sex Characteristics
PubMed: 34474722
DOI: 10.3967/bes2021.086 -
BMC Women's Health Apr 2023Iron deficiency anemia is a common public health issue among women of reproductive age (WRA) because it can result in adverse maternal and birth outcomes. Although... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Iron deficiency anemia is a common public health issue among women of reproductive age (WRA) because it can result in adverse maternal and birth outcomes. Although studies are undertaken to assess iron efficacy, some gaps and limitations in the existing literature need to be addressed. To fill the gaps, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the role of iron in reducing anemia among WRA in low-middle-income countries (LMICs).
METHODS
A comprehensive search strategy was used to search Medline through PubMed, Embase, and Science Direct for RCTs published between 2000 and 2020. The primary outcome was the mean change in hemoglobin level. We used standardized mean differences and their respective 95% CI to estimate the pooled effect. We used I statistics and Egger's test to assess heterogeneity and publication bias, respectively. This review was carried out in accordance with revised guidelines based on the Preferred Reporting Items for Systematic Review and Meta-analysis.
RESULTS
The findings showed that iron therapy improved hemoglobin and ferritin levels, though the results varied across studies. An overall pooled effect estimate for the role of iron therapy in improving the hemoglobin levels among WRA was -0.71 (95% CI: -1.27 to -0.14) (p = 0.008). Likewise, the overall pooled effect estimate for the role of iron therapy in improving the ferritin levels among WRA was -0.76 (95% CI: -1.56 to 0.04) (p = 0.04). The heterogeneity (I) across included studies was found to be statistically significant for studies assessing hemoglobin (Q = 746.93, I = 97.59%, p = 0.000) and ferritin level (Q = 659.95, I = 97.88%, p = 0.000).
CONCLUSION
Iron therapy in any form may reduce anemia's burden and improve hemoglobin and ferritin levels, indicating improvement in iron-deficiency anemia. More evidence is required, however, to assess the morbidity associated with iron consumption, such as side effects, work performance, economic outcomes, mental health, and adherence to the intervention, with a particular focus on married but non-pregnant women planning a pregnancy in the near future.
TRIAL REGISTRATION
Registered with PROSPERO and ID is CRD42020185033.
Topics: Pregnancy; Female; Humans; Iron; Developing Countries; Anemia, Iron-Deficiency; Anemia; Ferritins
PubMed: 37069552
DOI: 10.1186/s12905-023-02291-6 -
Seminars in Arthritis and Rheumatism Feb 2024The biomarkers for predicting the occurrence, progression, and death of idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) remain unclear.... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The biomarkers for predicting the occurrence, progression, and death of idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) remain unclear. Serum ferritin (SF) is a potential candidate and this systematic review and meta-analysis aimed to reveal the clinical significance of SF in IIM-ILD.
METHODS
Eligible English studies were selected from PubMed, Embase, Web of science and Scopus up to 9 June 2023. The SF levels in patients with IIM-ILD were extracted and pooled. Subgroup analysis was performed based on disease types, sensitivity analysis was conducted by excluding one class of literature at a time, and publication bias was assessed by funnel plot and Egger's test.
RESULTS
Pooled analysis of 1,933 patients with IIM from 19 studies showed that SF levels were significantly higher in IIM-ILD group (WMD=263.53ng/mL, 95% CI: 146.44-380.62, p<0.001) than IIM without ILD, subgroup analysis showed that SF levels in DM-ILD (WMD = 397.67ng/mL, 95% CI:142.84-652.50, p = 0.002) and PM/DM-ILD (WMD = 117.68 ng/mL, 95% CI: 86.32-149.04, p < 0.001) were significantly higher compared to those without ILD. SF levels were significantly higher in rapidly progressive interstitial lung disease group (RP-ILD)(WMD = 484.99 ng/mL, 95% CI: 211.12-758.87, p= 0.001) than chronic ILD(C-ILD) group, subgroup analysis showed that SF levels in DM-RP-ILD (WMD= 509.75 ng/mL, 95% CI: 215.34-804.16, p=0.001) were significantly higher than those in DM-C-ILD group. SF levels were significantly higher in death group (WMD= 722.16 ng/mL, 95% CI: 572.32-872.00, p< 0.001) compared to the survival group, subgroup analysis showed that death patients with DM-ILD(WMD= 735.62 ng/mL, 95% CI:574.92-896.32, p<0.001) and PM-ILD (WMD= 632.56 ng/mL, 95% CI:217.92-1047.19, p=0.003) had significantly higher SF levels than survival group respectively.
CONCLUSION
Increased SF levels can serve as a biomarker for predicting the occurrence, progression and death of patients with IIM-ILD, which can provide early warning sign for intervention and prognosis evaluation for IIM-ILD patients.
Topics: Humans; Myositis; Lung Diseases, Interstitial; Biomarkers; Prognosis; Ferritins; Retrospective Studies
PubMed: 38086199
DOI: 10.1016/j.semarthrit.2023.152350